Publications by authors named "Jiale Qin"

27 Publications

  • Page 1 of 1

Association between Serum Free Fatty Acids to HDL-Cholesterol Ratio and Nonalcoholic Fatty Liver Disease: a Cross-Sectional Study.

Clin Lab 2021 Sep;67(9)

Background: This cross-sectional study aimed to investigate the association between serum free fatty acids and high-density lipoprotein-cholesterol ratio (FHR) and nonalcoholic fatty liver disease (NAFLD) in a Chinese population.

Methods: A total of 760 NAFLD subjects and 379 healthy controls who took their annual health checkups were enrolled during 2019. Fasting blood samples were obtained from the population. NAFLD was diagnosed based on hepatic ultrasound examination.

Results: Serum FHR (*100) in NAFLD subjects was significantly higher than that in controls. We found that the serum FHR in NAFLD participants was positively correlated with BMI, DBP, WBC, HGB, ALT, AST, GGT, TG, FPG, UA, and hsCRP. Univariate and multivariate logistic regression analysis showed that FHR was independently associated with the presence of NAFLD. The area under curve (AUC) of the receiver operating characteristic (ROC) curve of FHR for NAFLD was 0.781 with the 95% confidence interval from 0.753 to 0.810. The optimal cutoff point of FHR for predicting NAFLD was 41.14 with 78.8% sensitivity and 77.3%, respectively.

Conclusions: FHR was significantly associated with NAFLD and may serve as an effective indicator in NAFLD patients.
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http://dx.doi.org/10.7754/Clin.Lab.2021.210109DOI Listing
September 2021

Nucleoside transporter-guided cytarabine-conjugated liposomes for intracellular methotrexate delivery and cooperative choriocarcinoma therapy.

J Nanobiotechnology 2021 Jun 15;19(1):184. Epub 2021 Jun 15.

Department of Pharmacy, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China.

Gestational trophoblastic tumors seriously endanger child productive needs and the health of women in childbearing age. Nanodrug-based therapy mediated by transporters provides a novel strategy for the treatment of trophoblastic tumors. Focusing on the overexpression of human equilibrative nucleoside transporter 1 (ENT1) on the membrane of choriocarcinoma cells (JEG-3), cytarabine (Cy, a substrate of ENT1)-grafted liposomes (Cy-Lipo) were introduced for the targeted delivery of methotrexate ([email protected]) for choriocarcinoma therapy in this study. ENT1 has a high affinity for Cy-Lipo and can mediate the endocytosis of the designed nanovehicles into JEG-3 cells. The ENT1 protein maintains its transportation function through circulation and regeneration during endocytosis. Therefore, Cy-Lipo-based formulations showed high tumor accumulation and retention in biodistribution studies. More importantly, the designed DSPE-PEG-Cy conjugation exhibited a synergistic therapeutic effect on choriocarcinoma. Finally, [email protected] exerted an extremely powerful anti-choriocarcinoma effect with fewer side effects. This study suggests that the overexpressed ENT1 on choriocarcinoma cells holds great potential as a high-efficiency target for the rational design of active targeting nanotherapeutics.
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http://dx.doi.org/10.1186/s12951-021-00931-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8207694PMC
June 2021

Prediction of neoadjuvant chemotherapy response in high-grade osteosarcoma: added value of non-tumorous bone radiomics using CT images.

Quant Imaging Med Surg 2021 Apr;11(4):1184-1195

Nuclear & Radiological Engineering and Medical Physics Programs, Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, USA.

Background: This study aimed to determine the impact of including radiomics analysis of non-tumorous bone region of interest in improving the performance of pathological response prediction to chemotherapy in high-grade osteosarcomas (HOS), compared to radiomics analysis of tumor region alone.

Methods: This retrospective study included 157 patients diagnosed with HOS between November 2013 and November 2017 (age range, 5-44 years; mean age, 16.99 ±7.42 years), in which 69 and 88 patients were diagnosed as pathological good response (pGR) and non-pGR, respectively. Radiomics features were extracted from tumor and non-tumorous bone regions based on diagnostic CT images. Pathological response classifiers were developed and validated via leave-one-out cross validation (LOOCV) and independent validation methods by using the area under the receiver operating characteristic curve (AUC) value as the figure of merit.

Results: Using the LOOCV, the classifiers combining features from tumor and non-tumorous regions showed better prediction performance than those from tumor region alone (AUC, 0.8207±0.0043 0.7799±0.0044). The combined classifier also showed better performance than the tumor feature-based classifier in both training and validation datasets [training dataset: 0.791, 95% confidence interval (CI), 0.706-0.860 0.766, 95% CI, 0.679-0.840; validation dataset: 0.816, 95% CI, 0.662-0.920 0.766, 95% CI, 0.606-0.885].

Conclusions: Radiomics analysis of combined tumor and non-tumorous bone features showed improved performance of pathological response prediction to chemotherapy in HOS compared to that of tumor features alone. Moreover, the proposed classifier had the potential to predict pathological response to chemotherapy for HOS patients.
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http://dx.doi.org/10.21037/qims-20-681DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930704PMC
April 2021

Multi-Material Decomposition for Single Energy CT Using Material Sparsity Constraint.

IEEE Trans Med Imaging 2021 05 30;40(5):1303-1318. Epub 2021 Apr 30.

Multi-material decomposition (MMD) decomposes CT images into basis material images, and is a promising technique in clinical diagnostic CT to identify material compositions within the human body. MMD could be implemented on measurements obtained from spectral CT protocol, although spectral CT data acquisition is not readily available in most clinical environments. MMD methods using single energy CT (SECT), broadly applied in radiological departments of most hospitals, have been proposed in the literature while challenged by the inferior decomposition accuracy and the limited number of material bases due to the constrained material information in the SECT measurement. In this paper, we propose an image-domain SECT MMD method using material sparsity as an assistance under the condition that each voxel of the CT image contains at most two different elemental materials. L norm represents the material sparsity constraint (MSC) and is integrated into the decomposition objective function with a least-square data fidelity term, total variation term, and a sum-to-one constraint of material volume fractions. An accelerated primal-dual (APD) algorithm with line-search scheme is applied to solve the problem. The pixelwise direct inversion method with the two-material assumption (TMA) is applied to estimate the initials. We validate the proposed method on phantom and patient data. Compared with the TMA method, the proposed MSC method increases the volume fraction accuracy (VFA) from 92.0% to 98.5% in the phantom study. In the patient study, the calcification area can be clearly visualized in the virtual non-contrast image generated by the proposed method, and has a similar shape to that in the ground-truth contrast-free CT image. The high decomposition image quality from the proposed method substantially facilitates the SECT-based MMD clinical applications.
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http://dx.doi.org/10.1109/TMI.2021.3051416DOI Listing
May 2021

Role of prenatal imaging in the diagnosis and management of fetal facio-cervical masses.

Sci Rep 2021 01 14;11(1):1385. Epub 2021 Jan 14.

Department of Radiology, Women's Hospital, Zhejiang University School of Medicine, Xueshi Rd No. 1, Hangzhou, Zhejiang, People's Republic of China.

Congenital facio-cervical masses can be a developmental anomaly of cystic, solid, or vascular origin, and have an inseparable relationship with adverse prognosis. This retrospective cross-sectional study aimed at determining on the prenatal diagnosis of congenital facio-cervical masses, its management and outcome in a large tertiary referral center. We collected information on prenatal clinical data, pregnancy outcomes, survival information, and final diagnosis. Out of 130 cases of facio-cervical masses, a total of 119 cases of lymphatic malformations (LMs), 2 cases of teratoma, 2 cases of thyroglossal duct cyst, 4 cases of hemangioma, 1 case of congenital epulis, and 2 cases of dermoid cyst were reviewed. The accuracy of prenatal ultrasound was 93.85% (122/130). Observations of diameters using prenatal ultrasound revealed that the bigger the initial diameter is, the bigger the relative change during pregnancy. Magnetic resonance imaging (MRI) revealed that 2 cases of masses were associated with airway compression. In conclusion, ultrasound has a high overall diagnostic accuracy of fetal face and neck deformities. Prenatal US can enhance the management of ambulatory monitoring and classification. Furthermore, MRI provided a detailed assessment of fetal congenital malformations, as well as visualization of the trachea, presenting a multi-dimensional anatomical relationship.
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http://dx.doi.org/10.1038/s41598-021-80976-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809128PMC
January 2021

High-speed parameter search of dynamic biological pathways from time-course transcriptomic profiles using high-level Petri net.

Biosystems 2021 Mar 1;201:104332. Epub 2021 Jan 1.

Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan.

Dynamic simulation promises a deeper understanding of complex molecular mechanisms of biological pathways. How to determine the reaction kinetic parameters which govern the simulation results is still an open question in the field of systems biology. (1) Background: To execute simulation experiments, it is an essential first step to search effective values of model parameters. The complexity of biological systems and the experimental measurement technology severely limit the acquirement of accurate kinetic parameters. Previously proposed genomic data assimilation (GDA) approach enables users to handle parameter estimation using time-course information. However, it highly depends on successive time points and costs massive computational resource; (2) Methods: To address this problem, we present a new high-speed parameter search method for estimating the kinetic parameters of quantitative biological pathways using time-course transcriptomic profiles. The key idea of our method is to interactively prune the search space by introducing Probabilistic Linear-time Temporal Logic (PLTL) based model checking into GDA. (3) Results and conclusion: We demonstrated the effectiveness of our method by comparing with GDA on Mus musculus transcription circuits modelled by hybrid functional Petri net with extension. As a result, our method works faster and more accurate than GDA for both time-course datasets with dense and sparse observed values.
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http://dx.doi.org/10.1016/j.biosystems.2020.104332DOI Listing
March 2021

KVarPredDB: a database for predicting pathogenicity of missense sequence variants of keratin genes associated with genodermatoses.

Hum Genomics 2020 12 7;14(1):45. Epub 2020 Dec 7.

Department of Human Genetics, and Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Background: Germline variants of ten keratin genes (K1, K2, K5, K6A, K6B, K9, K10, K14, K16, and K17) have been reported for causing different types of genodermatoses with an autosomal dominant mode of inheritance. Among all the variants of these ten keratin genes, most of them are missense variants. Unlike pathogenic and likely pathogenic variants, understanding the clinical importance of novel missense variants or variants of uncertain significance (VUS) is the biggest challenge for clinicians or medical geneticists. Functional characterization is the only way to understand the clinical association of novel missense variants or VUS but it is time consuming, costly, and depends on the availability of patient's samples. Existing databases report the pathogenic variants of the keratin genes, but never emphasize the systematic effects of these variants on keratin protein structure and genotype-phenotype correlation.

Results: To address this need, we developed a comprehensive database KVarPredDB, which contains information of all ten keratin genes associated with genodermatoses. We integrated and curated 400 reported pathogenic missense variants as well as 4629 missense VUS. KVarPredDB predicts the pathogenicity of novel missense variants as well as to understand the severity of disease phenotype, based on four criteria; firstly, the difference in physico-chemical properties between the wild type and substituted amino acids; secondly, the loss of inter/intra-chain interactions; thirdly, evolutionary conservation of the wild type amino acids and lastly, the effect of the substituted amino acids in the heptad repeat. Molecular docking simulations based on resolved crystal structures were adopted to predict stability changes and get the binding energy to compare the wild type protein with the mutated one. We use this basic information to determine the structural and functional impact of novel missense variants on the keratin coiled-coil heterodimer. KVarPredDB was built under the integrative web application development framework SSM (SpringBoot, Spring MVC, MyBatis) and implemented in Java, Bootstrap, React-mutation-mapper, MySQL, Tomcat. The website can be accessed through http://bioinfo.zju.edu.cn/KVarPredDB . The genomic variants and analysis results are freely available under the Creative Commons license.

Conclusions: KVarPredDB provides an intuitive and user-friendly interface with computational analytical investigation for each missense variant of the keratin genes associated with genodermatoses.
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http://dx.doi.org/10.1186/s40246-020-00295-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7720490PMC
December 2020

Associations between molybdenum exposure and ultrasound measures of fetal growth parameters: A pilot study.

Chemosphere 2021 Apr 22;269:128709. Epub 2020 Oct 22.

Department of Ultrasound, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China; Key Laboratory of Reproductive Genetics (Ministry of Education), Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China. Electronic address:

Previous studies have suggested the association of molybdenum (Mo) exposure with some adverse outcomes. However, limited epidemiological studies have been performed to explore the association between maternal Mo exposure level and fetal growth. This study recruited 220 pregnant women during their second trimester. The mother's urinary Mo concentration was measured by inductively coupled plasma mass spectrometry (ICP-MS). The fetal biometric parameters, including head circumference (HC), biparietal diameter (BPD), femur diaphysis length (FL), and abdominal circumference (AC) were assessed by prenatal ultrasound. Estimated fetal weight (EFW) was evaluated using the formula of Hadlock. Multivariable linear regression models were applied to estimate the relationships between Mo level and fetal biometric parameters, and potential confounders were adjusted. A one-unit increment in natural-logarithm transformed urinary Mo level was significantly associated with reductions in fetal AC of -0.34 cm (95%CI: -0.63, -0.04), and was negatively related to EFW (β = -18.2, 95%CI: -40.5, 4.2). Furthermore, when participants were stratified by copper (Cu) level, the results showed that the magnitude of negative association between Mo and AC (β = -0.55, 95%CI: -1.13, 0.04) was greater in pregnant women with Cu level below median value, comparing with those with Cu level above median value (β = -0.08, 95%CI: -0.57, 0.42), and a similar pattern was found for EFW, although the interaction between Mo and Cu was not significant. Our data suggested an inverse association of maternal urinary Mo level with fetal AC and EFW during the second trimester of pregnancy. These associations might be stronger in pregnant women with relatively lower Cu levels.
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http://dx.doi.org/10.1016/j.chemosphere.2020.128709DOI Listing
April 2021

Serum Thyroid Hormones Levels are Significantly Associated with Nonalcoholic Fatty Liver Disease in Euthyroid Chinese Population.

Clin Lab 2020 Oct;66(10)

Background: Thyroid hormones play an essential role in metabolic homeostasis. Previous studies have demon-strated a close relationship between thyroid abnormalities and metabolic disorders. This retrospective cross-sectional study was to investigate whether significant differences of circulating thyroid profiles exist and to explore the potential of serum thyroid hormones in reflecting advanced fibrosis in subjects with Nonalcoholic Fatty Liver Disease (NAFLD).

Methods: Abdominal ultrasonography was performed to diagnose NAFLD. For all the participants including 522 NAFLD patients and 415 gender- and age-matched controls recruited, demographic, clinical data and thyroid functions were recorded. Fasting serum thyroid hormones including free triiodothyronine (FT3), free thyroxine (FT4), total thyroxine (TT4), total triiodothyronine (TT3), and thyroid-stimulating hormone (TSH) were evaluated.

Results: Serum FT3 levels in subjects with NAFLD were significantly reduced, while TSH was increased compared to that in controls. The NAFLD subjects with metabolic syndrome (MS) had significantly lower FT3 and FT4 levels and higher TSH levels than the non-MS group. Serum TSH levels were positively associated with the risk for NAFLD, while FT3 levels were inversely correlated with NAFLD. Among thyroid hormones, low serum FT4 was the only independent predictor of reflecting advanced fibrosis in NAFLD participants.

Conclusions: An altered thyroid profile not only can be significantly associated with an increased incidence of NAFLD, but also had clinical predictive value for assessing significant fibrosis.
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http://dx.doi.org/10.7754/Clin.Lab.2020.200219DOI Listing
October 2020

A comprehensive evaluation of computational tools to identify differential methylation regions using RRBS data.

Genomics 2020 11 24;112(6):4567-4576. Epub 2020 Jul 24.

Department of Respiratory Medicine, Sir Run Run Shaw Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, China; Center of Systems Molecular Medicine, Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA. Electronic address:

DNA methylation plays a vital role in transcription regulation. Reduced representation bisulfite sequencing (RRBS) is becoming common for analyzing genome-wide methylation profiles at the single nucleotide level. A major goal of RRBS studies is to detect differentially methylated regions (DMRs) between different biological conditions. The previous tools to predict DMRs lack consistency. Here, we simulated RRBS datasets with significant attributes of real sequencing data under a wide range of scenarios, and systematically evaluated seven DMR detection tools in terms of type I error rate, precision/recall (PR), and area under ROC curve (AUC) using different methylation levels, sequencing coverage depth, length of DMRs, read length, and sample sizes. DMRfinder, methylSig, and methylKit were our preferred tools for RRBS data analysis, in terms of their AUC and PR curves. Our comparison highlights the different applicability of DMR detection tools and provides information to guide researchers towards the advancement of sequence-based DMR analysis.
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http://dx.doi.org/10.1016/j.ygeno.2020.07.032DOI Listing
November 2020

Integrating tumor and nodal radiomics to predict lymph node metastasis in gastric cancer.

Radiother Oncol 2020 09 10;150:89-96. Epub 2020 Jun 10.

Nuclear & Radiological Engineering and Medical Physics Programs, Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, USA. Electronic address:

Background: To develop and validate a radiomics method via integrating tumor and lymph node radiomics for the preoperative prediction of lymph node (LN) status in gastric cancer (GC).

Materials And Methods: We retrospectively collected 170 contrast-enhanced abdominal CT images from GC patients. Five times repeated random hold-out experiment was employed. Tumor and nodal radiomics features were extracted from each individual tumor and LN respectively, and then multi-step feature selection was performed. The optimal tumor and nodal features were selected using Pearson correlation analysis and sequential forward floating selection (SFFS) algorithm. After feature fusion, the SFFS algorithm was used to develop radiomics signatures. The performance of the radiomics signatures developed based on logistic regression classifier was further analyzed and compared using the area under the receiver operating characteristic curve (AUC).

Results: The AUC values, reported as mean ± standard deviation, were 0.9319 ± 0.0129 and 0.8546 ± 0.0261 for the training and validation cohorts respectively. The radiomic signatures could predict LN status, especially in T2-stage, diffuse-type and moderately/well differentiated GC. After integrating clinicopathologic information, the radiomic-clinicopathologic model (training cohort, 0.9432 ± 0.0129; validation cohort, 0.8764 ± 0.0322) showed a better discrimination capability than other radiomics models and clinicopathologic model. The radiomic-clinicopathologic model also showed superior performance to the gastroenterologist' decision in all experiments, and outperformed the radiologist in some experiments.

Conclusion: Our proposed method presented good predictive performance and great potential for predicting LNM in GC. As a noninvasive preoperative prediction tool, it can be helpful for guiding the prognosis and treatment decision-making in GC patients.
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http://dx.doi.org/10.1016/j.radonc.2020.06.004DOI Listing
September 2020

Association Rule Learning Is an Easy and Efficient Method for Identifying Profiles of Traumas and Stressors that Predict Psychopathology in Disaster Survivors: The Example of Sri Lanka.

Int J Environ Res Public Health 2020 04 21;17(8). Epub 2020 Apr 21.

Faculty of Engineering and Information Technology, University of Technology Sydney, Ultimo, NSW 2007, Australia.

Research indicates that psychopathology in disaster survivors is a function of both experienced trauma and stressful life events. However, such studies are of limited utility to practitioners who are about to go into a new post-disaster setting as (1) most of them do not indicate which specific traumas and stressors are especially likely to lead to psychopathology; and (2) each disaster is characterized by its own unique traumas and stressors, which means that practitioners have to first collect their own data on common traumas, stressors and symptoms of psychopathology prior to planning any interventions. An easy-to-use and easy-to-interpret data analytical method that allows one to identify profiles of trauma and stressors that predict psychopathology would be of great utility to practitioners working in post-disaster contexts. We propose that association rule learning (ARL), a big data mining technique, is such a method. We demonstrate the technique by applying it to data from 337 survivors of the Sri Lankan civil war who completed the Penn/RESIST/Peradeniya War Problems Questionnaire (PRPWPQ), a comprehensive, culturally-valid measure of experienced trauma, stressful life events, anxiety and depression. ARL analysis revealed five profiles of traumas and stressors that predicted the presence of some anxiety, three profiles that predicted the presence of severe anxiety, four profiles that predicted the presence of some depression and five profiles that predicted the presence of severe depression. ARL allows one to identify context-specific associations between specific traumas, stressors and psychological distress, and can be of great utility to practitioners who wish to efficiently analyze data that they have collected, understand the output of that analysis, and use it to provide psychosocial aid to those who most need it in post-disaster settings.
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http://dx.doi.org/10.3390/ijerph17082850DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7215723PMC
April 2020

The 16-year experience in treating low-risk gestational trophoblastic neoplasia patients with failed primary methotrexate chemotherapy.

J Gynecol Oncol 2020 Jul 7;31(4):e36. Epub 2020 Jan 7.

Department of Gynecologic Oncology, Women's Hospital, School of Medicine Zhejiang University, Hangzhou, China.

Objective: To assess the outcomes and toxic effects of 5-day actinomycin D (Act-D) salvage therapy and to explore the predictors of Act-D resistance in patients with low-risk gestational trophoblastic neoplasia (GTN)who failed 5-day methotrexate (MTX) chemotherapy.

Methods: This retrospective study analyzed patients with low-risk GTN administered Act-D salvage therapy after failing MTX chemotherapy at Women's Hospital, School of Medicine Zhejiang University between January 2000 and December 2015. The clinical parameters of these patients were collected and analyzed.

Results: The final analysis included 89 cases. Of these, 73 cases (82.02%) responded to salvage Act-D. The remaining 16 resistant cases were switched to etoposide, MTX, Act-D/cyclophosphamide, and vincristine chemotherapy and achieved complete remission. Serum human chorionic gonadotrophin levels before Act-D salvage therapy (hCG)in the Act-D-resistant cases were significantly higher than those in the Act-D responders (median 605 vs. 103 IU/L, p=0.009). However, the range of hCG values in Act-D responders was wider than that in Act-D-resistant cases (5.76-16,664 IU/L vs. 11.43-6,732 IU/L). Thus, assigning a general cut-off value was difficult considering the individual setting. Except for 2 cases requiring other salvage regimens due to Act-D toxicity, 97.80% of cases (89/91) tolerated the toxicity. During at least 1-year follow-up, the survival rate was 100.00% and no case developed recurrence.

Conclusion: Based on the good therapeutic effect and tolerable toxicity, we recommend Act-D salvage therapy for all patients with low-risk GTN who fail primary MTX chemotherapy. The higher serum hCG levels before Act-D salvage therapy may be associated with resistance to this treatment.
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http://dx.doi.org/10.3802/jgo.2020.31.e36DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7286751PMC
July 2020

Thyroid cancer MR molecular imaging via SHP2-targeted nanoparticles.

Int J Nanomedicine 2019 10;14:7365-7373. Epub 2019 Sep 10.

Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, Jiangsu 210009, People's Republic of China.

Background: Molecular imaging has generated a great demand to develop targeted contrast agents for MR imaging.

Materials And Methods: In this study, we synthesized Src homology 2-containing phosphotyrosine phosphatase 2 (SHP2)-targeted and polylactic-co-glycolic acid--based nanoparticles (NPs), which encapsulated perfluoropentane and being chelated with gadolinium (Gd) as an efficient molecular probe for targeting MR imaging on thyroid carcinoma.

Results: These NPs displayed practical properties and favorable biocompatibility in vitro. Furthermore, they showed abilities to specifically target thyroid cancer and enhance MRI as a contrast agent in both in vitro and in vivo experiments.

Conclusion: This novel MR molecular imaging based on this SHP2-targeted contrast agent provides a useful and non-invasive method for the early detection of thyroid carcinoma.
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http://dx.doi.org/10.2147/IJN.S201358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6751334PMC
January 2020

Autophagy maintains the stemness of ovarian cancer stem cells by FOXA2.

J Exp Clin Cancer Res 2017 Nov 29;36(1):171. Epub 2017 Nov 29.

Department of Gynecologic Oncology; Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, 310006, China.

Background: Cancer stem cells (CSCs) are regarded as the main cell type responsible for the initiation, metastasis, drug resistance, and recurrence of cancer. But the mechanism by which cancer stem cells maintain their stemness remains unclear.

Methods And Results: In the present study, ovarian cancer stem cells (OCSCs) were revealed to have an enhanced autophagic flux. Furthermore, their chemoresistance and ability to self-renewal in vitro were decreased when autophagy was inhibited by Bafilomycin A1(BafA1), Chloroquine(CQ) or autophagy related 5(ATG5) knockdown. PCR array screening determined that Forkhead Box A2(FOXA2) was highly expressed in OCSCs, and correspondingly regulated by autophagy activity. In addition, the self-renewal ability was decreased in the case of FOXA2 knockdown by shRNA in OCSCs. Overexpression of FOXA2 from the pEGFP(+)-FOXA2 plasmid partially reversed the depressed self-renewal ability of OCSCs during autophagy inhibition.

Conclusions: Our findings suggest that autophagy, through participation of FOXA2, maintains the characteristics of OCSCs. Autophagy and FOXA2 are therefore potential targets for ovarian cancer stem cell directed therapies.
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http://dx.doi.org/10.1186/s13046-017-0644-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5707869PMC
November 2017

Roles of Mifepristone on the Regulation of Cytotoxic Lymphocytes and Regulatory T Cells.

Gynecol Obstet Invest 2017 28;82(6):533-537. Epub 2017 Oct 28.

Department of Obstetrics and Gynecology, Zhejiang University Hospital, Hangzhou, PR China.

Objective: To investigate the immunologic function of mifepristone, which acts as a contraceptive drug at the level of the decidua.

Setting: In our hospital, 60 women (less than 63 days of amenorrhea) volunteered to terminate their pregnancies by the uterine suction evacuation method. Immunohistochemically, the transcription factor forkhead box P3 and granzyme B staining were performed to identify regulatory T cells and cytotoxic lymphocytes (CLs) in all operational subjects. CD8 (cytotoxic T cells marker) and CD56 (natural killer cells marker) staining were further performed in order to characterize the CLs subpopulations.

Result: A significantly increased number of CLs was found in the decidua treated with mifepristone.

Conclusion: Mifepristone increases the expression of CLs in the decidua, and it provides new insights into the immunologic function of mifepristone as a drug used for pregnancy termination.
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http://dx.doi.org/10.1159/000455848DOI Listing
July 2018

A transcriptomic landscape of human papillomavirus 16 E6-regulated gene expression and splicing events.

FEBS Lett 2016 Dec 23;590(24):4594-4605. Epub 2016 Nov 23.

Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

The oncoprotein E6 of high-risk human papillomavirus (HPV) is responsible for the initiation and progression of cervical cancer. In the present study, we performed RNA-sequencing analysis in HPV16 E6-expressing 293T cells and identified 56 differentially expressed genes (DEGs) and a number of cellular pathways significantly affected. We confirmed nine of these DEGs in both cell models and clinical tissue samples. Furthermore, we performed de novo transcriptome assembly of 1128 novel human transcripts and identified 22 that are differentially expressed in the presence of HPV16 E6. In addition, our analysis revealed distinct alternative splicing events in response to HPV16 E6 expression. Overall, the present study provides a comprehensive portrait of transcriptional and splicing signatures, as well as previously unknown genes differentially expressed in response to HPV16 E6, which prompts the need for a complete annotation of the HPV16 E6-regulated transcriptome.
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http://dx.doi.org/10.1002/1873-3468.12486DOI Listing
December 2016

Prognostic value of pathological response to neoadjuvant chemotherapy in bulky stage Ib2 and IIa cervical squamous cell cancer patients.

Virchows Arch 2016 Mar 4;468(3):329-36. Epub 2015 Dec 4.

Department of Obstetrics and Gynecology, the Affiliated Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, 310006, People's Republic of China.

Neoadjuvant chemotherapy (NAC) is widely used to treat patients with locally advanced cervical cancer. Optimal pathological response to neoadjuvant therapy has proven to be a good prognostic indicator for patient survival, but the prognostic significance of a partial response remains unclear. The aim of this study was to identify prognostic predictors for patients with partial response. We included in the study 190 patients with bulky stage Ib2 or IIa cervical squamous cell cancer, who underwent neoadjuvant chemotherapy followed by surgery. A novel pathological grading system, including optimal response (complete disappearance of tumor, grade 1), viable tumor cells occupying <(2)/3 (grade 2) or >(2)/3 (grade 3) of the tumor bed area and extra-cervical tumor deposits (grade 4), was developed and associations with disease-free survival and overall survival were studied. Survival analysis was conducted using log-rank testing and Cox regression analysis. We found statistically significant differences between 4 different pathological response groups both in terms of disease-free survival (p = 0.001) and overall survival (p = 0.003). Combining adjacent survival curves in the pathological grading system allowed us to identify response grade 2 patients with disease-free and overall survival similar to those of optimal response patients (p = 0.000, p = 0.002). Multivariate analyses showed that the pathological response grading system is the only independent predictor for progression-free survival and overall survival (p = 0.001 and p = 0.007). A response grading system based on pathological parameters may be useful to predict both progression-free and overall survival in bulky stage Ib2 and IIa cervical squamous cell cancer patients treated with NAC.
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http://dx.doi.org/10.1007/s00428-015-1888-3DOI Listing
March 2016

Sonoporation: Applications for Cancer Therapy.

Adv Exp Med Biol 2016 ;880:263-91

Department of Radiology, Molecular Imaging Program at Stanford, Stanford University, School of Medicine, Stanford, CA, USA.

Therapeutic efficacy of both traditional chemotherapy and gene therapy in cancer is highly dependent on the ability to deliver drugs across natural barriers, such as the vessel wall or tumor cell membranes. In this regard, sonoporation induced by ultrasound-guided microbubble (USMB) destruction has been widely investigated in the enhancement of therapeutic drug delivery given it can help overcome these natural barriers, thereby increasing drug delivery into cancer. In this chapter we discuss challenges in current cancer therapy and how some of these challenges could be overcome using USMB-mediated drug delivery. We particularly focus on recent advances in delivery approaches that have been developed to further improve therapeutic efficiency and specificity of various cancer treatments. An example of clinical translation of USMB-mediated drug delivery is also shown.
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http://dx.doi.org/10.1007/978-3-319-22536-4_15DOI Listing
March 2016

Endometrial adenocarcinoma in spontaneous abortion: two cases and review of the literature.

Int J Clin Exp Med 2015 15;8(5):8230-3. Epub 2015 May 15.

Department of Obstetrics and Gynecology, Women's Hospital, School of Medicine, Zhejiang University Hangzhou, Zhejiang Province, China.

Objectives: To report two extremely rare cases of endometrial adenocarcinoma established during the first trimester.

Case Presentation: A 40-year-old (gravida 0, para 0) and 33-year-old (gravida 4, para 0) woman, were diagnosed with a well-differentiated adenocarcinoma after a dilatation and curettage (D&C) for spontaneous abortions at 8 and 9 gestational weeks, respectively.

Conclusions: Thirty-six cases of pregnancy-associated endometrial cancer and 20 cases of first trimester pregnancy concurrent with endometrial carcinoma have been reported as present cases in the literature. Interestingly, 15 including our two cases were detected for spontaneous abortions in first-trimester suggesting a causal correlation between endometrial adenocarcinoma and spontaneous abortions. Repeated D&C and progesterone administration may be appropriate for patients who wish to preserve fertility.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4509345PMC
July 2015

Three-dimensional Dynamic Contrast-enhanced US Imaging for Early Antiangiogenic Treatment Assessment in a Mouse Colon Cancer Model.

Radiology 2015 Nov 22;277(2):424-34. Epub 2015 May 22.

From the Department of Radiology, Molecular Imaging Program at Stanford (H.W., J.Q., J.K.W.), Department of Radiation Oncology (D.H.), and Department of Health, Research & Policy (L.T.), Stanford University School of Medicine, 300 Pasteur Dr, Room H1307, Stanford, CA 94305-5621.

Purpose: To evaluate feasibility and reproducibility of three-dimensional (3D) dynamic contrast material-enhanced (DCE) ultrasonographic (US) imaging by using a clinical matrix array transducer to assess early antiangiogenic treatment effects in human colon cancer xenografts in mice.

Materials And Methods: Animal studies were approved by the Institutional Administrative Panel on Laboratory Animal Care at Stanford University. Three-dimensional DCE US imaging with two techniques (bolus and destruction-replenishment) was performed in human colon cancer xenografts (n = 38) by using a clinical US system and transducer. Twenty-one mice were imaged twice to assess reproducibility. Seventeen mice were scanned before and 24 hours after either antiangiogenic (n = 9) or saline-only (n = 8) treatment. Data sets of 3D DCE US examinations were retrospectively segmented into consecutive 1-mm imaging planes to simulate two-dimensional (2D) DCE US imaging. Six perfusion parameters (peak enhancement [PE], area under the time-intensity curve [AUC], time to peak [TTP], relative blood volume [rBV], relative blood flow [rBF], and blood flow velocity) were measured on both 3D and 2D data sets. Percent area of blood vessels was quantified ex vivo with immunofluorescence. Statistical analyses were performed with the Wilcoxon rank test by calculating intraclass correlation coefficients and by using Pearson correlation analysis.

Results: Reproducibility of both 3D DCE US imaging techniques was good to excellent (intraclass correlation coefficient, 0.73-0.86). PE, AUC, rBV, and rBF significantly decreased (P ≤ .04) in antiangiogenic versus saline-treated tumors. rBV (r = 0.74; P = .06) and rBF (r = 0.85; P = .02) correlated with ex vivo percent area of blood vessels, although the statistical significance of rBV was not reached, likely because of small sample size. Overall, 2D DCE-US overestimated and underestimated treatment effects from up to 125-fold to170-fold compared with 3D DCE US imaging. If the central tumor plane was assessed, treatment response was underestimated up to threefold or overestimated up to 57-fold on 2D versus 3D DCE US images.

Conclusion: Three-dimensional DCE US imaging with a clinical matrix array transducer is feasible and reproducible to assess tumor perfusion in human colon cancer xenografts in mice and allows for assessment of early treatment response after antiangiogenic therapy.
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http://dx.doi.org/10.1148/radiol.2015142824DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4627439PMC
November 2015

Atypical postcesarean epithelioid trophoblastic lesion with cyst formation: a case report and literature review.

Hum Pathol 2015 Jul 19;46(7):1036-9. Epub 2015 Feb 19.

Department of Obstetrics and Gynecology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310006, China. Electronic address:

We report an extremely rare case of atypical postcesarean epithelioid trophoblastic lesion with cyst formation. A 41-year-old Chinese woman presented with lower abdominal pain and menstrual disorder. Her serum human chorionic gonadotropin (hCG) was low (0.373 IU/L), and her urine hCG was negative. Ultrasound images showed a 3.7×2.8×2.5 cm(3) mass on the surface of the lower uterine segment, and a laparoscopy indicated a cystic mass in the serosal surface of the lower uterine segment. Histology indicated a cystic lesion consisting of epithelioid trophoblastic cells with an intermediate pattern between a classical placental site nodule and an epithelioid trophoblastic tumor; thus, the term atypical postcesarean epithelioid trophoblastic lesion with cyst formation was appropriate. As in atypical placental site nodule, serum hCG monitoring after treatment is necessary.
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http://dx.doi.org/10.1016/j.humpath.2014.10.031DOI Listing
July 2015

Methotrexate management for placenta accreta: a prospective study.

Arch Gynecol Obstet 2015 Jun 11;291(6):1259-64. Epub 2014 Dec 11.

Department of Gynecology, Women's Hospital, Zhejiang University School of Medicine, 1 Xueshi Road, Hangzhou, 310006, Zhejiang, People's Republic of China.

Objective: To observe efficacy following methotrexate (MTX) management in women with placenta accreta.

Methods: Twenty-four stable patients with placenta accreta were treated with MTX. Beta-hCG values, vascular indices of the residual placenta, and other clinical characteristics were collected prospectively and were compared between the success and failure groups.

Results: After MTX management, the residual placentas were expulsed spontaneously in 33.3% of the patients. This was done through dilatation and curettage (D & C) in 45.8% of the patients. The residuals in the uterine wall were completely absorbed within 5.7 months. In the patients who were successfully treated with MTX, their beta-hCG values and vascular indices of the placentas decreased faster than those of failure patients (P < 0.05). Those (20.8%) failing MTX management and subsequent D & C showed that their vascular indices persisted high levels and some even experienced elevations despite significantly decreased hCG values.

Conclusions: MTX management, when the beta-hCG value and vascular indices of placenta decreased significantly, is a conservative option for a stable patient with placenta accreta in China. 3D power Doppler ultrasound should be utilized for the follow-up of this condition.
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http://dx.doi.org/10.1007/s00404-014-3573-1DOI Listing
June 2015

A well-circumscribed border with peripheral Doppler signal in sonographic image distinguishes epithelioid trophoblastic tumor from other gestational trophoblastic neoplasms.

PLoS One 2014 14;9(11):e112618. Epub 2014 Nov 14.

Department of Oncology, Women's Hospital, School of Medicine, Zhejiang University, Zhejiang, China.

As epithelioid trophoblastic tumor (ETT) shares similar clinical features with other gestational trophoblastic neoplasms (GTNs), it is likely to be clinically misdiagnosed and subsequently treated in an improper way. This study aimed to identify the sonographic features of ETT that are distinct from other GTNs, including placental site trophoblastic tumor (PSTT) and invasive mole/choriocarcinoma (IM/CC). Here, we retrospectively analyzed ultrasound images of 12 patients with ETT in comparison with those of 21 patients with PSTT and 24 patients with IM/CC. The results showed that maximal diameter and hemodynamic parameters were not significantly different among ETT, PSTT and IM/CC (P>0.05). However, a well-circumscribed border with hypoechogenic halo was identified in the gray-scale sonogram in all 12 cases of ETT, while only in 1 out of 21 cases of PSTT and 1 out of 16 cases of IM/CC (P<0.001 for ETT vs. PSTT or IM/CC). Moreover, a peripheral pattern of Doppler signals was observed in 11 out of 12 ETT lesions, showing relatively more Doppler signal spots around the tumor border than within the boundary, while a non-peripheral pattern of Doppler signals in all 21 PSTT cases and 14 out of 16 IM/CC cases: with minimal, moderate or remarkable signal spots within the tumor, but not along the tumor (P<0.001 for ETT vs. PSTT or IM/CC). These distinct sonographic features of ETT correlated with histopathologic observations, such as expansive growth pattern and vascular morphology. Thus, we draw the conclusions that the well-circumscribed border with peripheral Doppler signal may serve as a reliable sonographic feature to discriminate ETT from other types of GTNs. With further validation in a larger patient set in our ongoing multi-center study, this finding will be potentially developed into a non-invasive pre-operative GTN subtyping method for ETT.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0112618PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4232420PMC
December 2015

Multiple genital tract tumors and mucinous adenocarcinoma of colon in a woman with Peutz-Jeghers syndrome: a case report and review of literatures.

Int J Clin Exp Pathol 2014 15;7(7):4448-53. Epub 2014 Jun 15.

Department of Obstetrics and Gynecology, Women's Hospital, School of Medicine, Zhejiang University Hangzhou, Zhejiang Province, China.

We report a very rare case of Peutz-Jeghers syndrome (PJS) composed of multiple genital tract tumors and mucinous adenocarcinoma. A 46-year-old woman presented to our hospital with lower abdominal pain resulting from PJS involves sex cord tumor with annular tubules (SCTAT), ovarian mucinous tumor, ovarian serous tumor, mucinous adenocarcinoma of colon. The CEA concentration is high before surgery, and decreases after the surgery and subsequent chemoradiotherapy. This case demonstrates a classic clinical presentation of a patient with PJS. PJS patients have increased risk of malignancy and early detection and regular surveillance of the high-risk patients with PJS is crucial. Surgery may be required for obstructive gastrointestinal lesions as well as those exhibiting malignant degeneration.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4129067PMC
May 2015

Simultaneous osseous metaplasia nodules of the submucosa and mesosalpinx after first trimester abortion: a case report.

Eur J Med Res 2013 Nov 19;18:47. Epub 2013 Nov 19.

Department of Obstetrics and Gynecology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, 1 Xueshi Road, Hangzhou, Zhejiang Province 310006, People's Republic of China.

Objectives: Here, we report a case of simultaneous osseous metaplasia nodules of the submucosa and mesosalpinx after a first trimester abortion.

Case Presentation: A 36-year-old woman presented to the Women's Hospital, School of Medicine, Zhejiang University with vaginal bleeding and infertility resulting from osseous metaplasia nodules of the submucosa and mesosalpinx after a first trimester abortion. Diagnostic and operative hysteroscopy and laparoscope procedures were performed. The osseous metaplasia nodules disappeared after hysteroscopy and laparoscope interventions; 2 weeks postoperatively, the patient underwent a transvaginal ultrasound examination and the abnormal ultrasound appearance had resolved.

Conclusions: Osseous metaplasia nodules in the submucosa and mesosalpinx can be a rare cause of vaginal bleeding and infertility. Autologous tissue, not persistent heterologous tissue, may be the true reason for metaplasia. Treatment is by ultrasound-guided curettage or by hysteroscopic and laparoscope removal.
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http://dx.doi.org/10.1186/2047-783X-18-47DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4176990PMC
November 2013

Comparison of reproducibility of manual and sphere contour methods for the measurement of vascularization in cervical carcinoma using the virtual organ computer-aided analysis II system.

J Ultrasound Med 2010 Dec;29(12):1801-10

Department of Ultrasound, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.

Objective: The purpose of this study was to investigate the reproducibility of virtual organ computer-aided analysis II software (GE Healthcare, Milwaukee, WI), an integrated tool for 3-dimensional power Doppler angiography (3D-PDA), in measuring vascularization of cervical carcinoma under manual and automatic sphere contour modes.

Methods: Eighty patients with cervical carcinoma were prospectively examined by observer 1 using transvaginal 3D-PDA. For each patient, measurements of the vascularization index, flow index, and vascularization-flow index were repeated twice under both manual and automatic sphere contour modes. Forty patients were randomly selected for another round of examination by observer 2 under the same setting. The reproducibility of vascularization measurements was assessed by the intraclass correlation coefficient (intra-CC), interclass correlation coefficient (inter-CC), and 95% limits of agreement (LOAs). Various analysis of variance models were used to estimate the contribution of each factor (observer, contour mode, and patient) to measurement variance.

Results: For each observer, the manual contour mode outperformed the automatic sphere contour mode in reproducibility (intra-CC, 0.96 to 0.99 versus 0.77 to 0.94). In addition, repeated measurements of the manual mode had a smaller SD and a narrower LOA. For the manual contour mode, interobserver agreement was comparable with intraobserver agreement (inter-CC, 0.91 to 0.98, versus intra-CC, 0.96 to 0.99). However, the interobserver agreement was significantly smaller than the intraobserver agreement for the automatic sphere contour mode (inter-CC, 0.51 to 0.85, versus intra-CC, 0.77 to 0.94; P = .001).

Conclusions: The manual contour mode for 3D-PDA vascular measurements has better interobserver and intraobserver reproducibility than the automatic sphere contour mode. It is especially useful for measuring tumor tissues with irregular shapes and vascularity.
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http://dx.doi.org/10.7863/jum.2010.29.12.1801DOI Listing
December 2010
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