JZJing Zhao
Papers(6)
Unsupervised cervical…A Clinical Prediction…Identification of <sc…Engineering Bifunctio…Carrier-free multifun…Tumor cell-derived ex…
Collaborators(4)
Na LiYazhuo WangZehua WangJing Cai
Institutions(4)
Hunan Provincial Mate…Peter MacCallum Cance…Hebei General HospitalHuazhong University O…

Papers

Unsupervised cervical cell instance segmentation method integrating cellular characteristics

Cell instance segmentation is a key technology for cervical cancer auxiliary diagnosis systems. However, pixel-level annotation is time-consuming and labor-intensive, making it difficult to obtain a large amount of annotated data. This results in the model not being fully trained. In response to these problems, this paper proposes an unsupervised cervical cell instance segmentation method that integrates cell characteristics. Cervical cells have a clear corresponding structure between the nucleus and cytoplasm. This method fully takes this feature into account by building a dual-flow framework to locate the nucleus and cytoplasm and generate high-quality pseudo-labels. In the nucleus segmentation stage, the position and range of the nucleus are determined using the standard cell-restricted nucleus segmentation method. In the cytoplasm segmentation stage, a multi-angle collaborative segmentation method is used to achieve the positioning of the cytoplasm. First, taking advantage of the self-similarity characteristics of pixel blocks in cells, a cytoplasmic segmentation method based on self-similarity map iteration is proposed. The pixel blocks are mapped from the perspective of local details, and the iterative segmentation is repeated. Secondly, using low-level features such as cell color and shape, a self-supervised heatmap-aware cytoplasm segmentation method is proposed to obtain the activation map of the cytoplasm from the perspective of global attention. The two methods are fused to determine cytoplasmic regions, and combined with nuclear locations, high-quality pseudo-labels are generated. These pseudo-labels are used to train the model cyclically, and the loss strategy is used to encourage the model to discover new object masks, thereby obtaining a segmentation model with better performance. Experimental results show that this method achieves good results in cytoplasm segmentation. On the three datasets of ISBI, MS_CellSeg, and Cx22, 54.32%, 44.64%, and 66.52% AJI were obtained, respectively, which is better than other typical unsupervised methods selected in this article.

A Clinical Prediction Model for Pathologic Upgrade to Invasive Carcinoma Following Conization of Cervical High‐Grade Squamous Intraepithelial Lesions

ABSTRACT Objective To explore the risk factors associated with the pathological progression to invasive carcinoma following the conization of cervical high‐grade squamous intraepithelial lesions (HSIL) and to construct a risk prediction model to guide preoperative risk assessment and optimize the selection of surgical approaches. Methods A retrospective analysis was conducted on the clinical data of 3337 patients who underwent cervical conization for HSIL at Hunan Provincial Maternal and Child Health Care Hospital from December 2016 to March 2022. The patients were categorized into the pathological progression group (398 cases) and the nonprogression group (2939 cases) based on postconization pathology results. Statistical significance factors were selected by least absolute shrinkage and selection operator regression and then multivariate logistic regression was utilized to build predictive models, which were presented as a nomogram and evaluated for discriminability, calibration, and decision curves. The Bootstrap method was utilized for internal validation. A total of 277 patients were enrolled from April 2022 to October 2022 for external validation. Results The percentage of pathologic upgrades to invasive carcinoma following cervical conization was 11.9%. The predictive model included age, contact bleeding symptoms, HPV16/18 infection, HSIL cytology, cervical biopsy pathology diagnosis level, suspicious stromal infiltration in the biopsy pathology diagnosis, and endocervical curettage HSIL. The model demonstrated good overall discrimination in predicting the risk of HSIL progression to early invasive cancer, and internal validation confirmed its reliability (C‐index = 0.787). Area under the curve analysis indicated good model discriminability across external datasets. The decision curve analysis also suggested that this model is clinically useful. Conclusion We developed and validated a nomogram incorporating multiple clinically relevant variables to better identify cases of HSIL progressing to early cervical cancer, providing a basis for individualized treatment and surgical approach selection.

Engineering Bifunctional Calcium Alendronate Gene‐Delivery Nanoneedle for Synergistic Chemo/Immuno‐Therapy Against HER2 Positive Ovarian Cancer

Abstract Ovarian cancer is the most lethal gynecological malignancy. Most patients are diagnosed at an advanced stage with widespread peritoneal dissemination and ascites. Bispecific T‐cell engagers (BiTEs) have demonstrated impressive antitumor efficacy in hematological malignancies, but the clinical potency is limited by their short half‐life, inconvenient continuous intravenous infusion, and severe toxicity at relevant therapeutic levels in solid tumors. To address these critical issues, the design and engineering of alendronate calcium (CaALN) based gene‐delivery system is reported to express therapeutic level of BiTE (HER2×CD3) for efficient ovarian cancer immunotherapy. Controllable construction of CaALN nanosphere and nanoneedle is achieved by the simple and green coordination reactions that the distinct nanoneedle‐like alendronate calcium (CaALN‐N) with a high aspect ratio enabled efficient gene delivery to the peritoneum without system in vivo toxicity. Especially, CaALN‐N induced apoptosis of SKOV3‐luc cell via down‐regulation of HER2 signaling pathway and synergized with HER2×CD3 to generate high antitumor response. In vivo administration of CaALN‐N/minicircle DNA encoding HER2×CD3 (MC‐HER2×CD3) produces sustained therapeutic levels of BiTE and suppresses tumor growth in a human ovarian cancer xenograft model. Collectively, the engineered alendronate calcium nanoneedle represents a bifunctional gene delivery platform for the efficient and synergistic treatment of ovarian cancer.

Carrier-free multifunctional nanomedicine for intraperitoneal disseminated ovarian cancer therapy

Abstract Background Ovarian cancer is the most lethal gynecological cancer which is characterized by extensive peritoneal implantation metastasis and malignant ascites. Despite advances in diagnosis and treatment in recent years, the five-year survival rate is only 25–30%. Therefore, developing multifunctional nanomedicine with abilities of promoting apoptosis and inhibiting migration on tumor cells would be a promising strategy to improve the antitumor effect. Methods and results In this study, we developed a novel ACaT nanomedicine composed of alendronate, calcium ions and cyclin-dependent kinase 7 (CDK7) inhibitor THZ1. With the average size of 164 nm and zeta potential of 12.4 mV, the spherical ACaT nanoparticles were selectively internalized by tumor cells and effectively accumulated in the tumor site. Results of RNA-sequencing and in vitro experiments showed that ACaT promoted tumor cell apoptosis and inhibited tumor cell migration by arresting the cell cycle, increasing ROS and affecting calcium homeostasis. Weekly intraperitoneally administered of ACaT for 8 cycles significantly inhibited the growth of tumor and prolonged the survival of intraperitoneal xenograft mice. Conclusion In summary, this study presents a new self-assembly nanomedicine with favorable tumor targeting, antitumor activity and good biocompatibility, providing a novel therapeutic strategy for advanced ovarian cancer. Graphical Abstract

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