Clinical significance of regulatory T cells and T lymphocyte subsets in peripheral blood in neoadjuvant chemotherapy for breast cancer.

The impact of the immune response on the therapeutical efficacy of neoadjuvant chemotherapy for breast cancer remains largely unknown. To characterize the role of regulatory T cells (CD4+CD25+CD127lowTreg), T lymphocyte subsets (CD3+, CD4+, CD4+/CD8+) and NK cells in neoadjuvant chemotherapy, we investigated the correlation patterns of these immune cell subsets with the progression of breast cancer. A total of 120 breast cancer patients receiving neoadjuvant chemotherapy in Nanjing Maternal and Child Health Hospital from May 2019 to November 2021 were retrospectively collected as the breast cancer group, and 46 healthy women were selected as the control group. The number of regulatory T cells, T lymphocyte subsets and NK cells in the peripheral blood were analyzed by flow cytometry. Compared with the control group, CD3+, CD4+, CD4+/CD8+ ratio and NK cells were significantly decreased in patients with breast cancer (P < 0.05), while the levels of Treg and CD8+ cells were significantly increased (P < 0.05). In addition, the status of the immune response among breast cancer patients at different clinical stages was obviously different. In higher tumor stages, the level of CD3+, CD4+, CD4+/CD8+ ratio and NK cell were reduced, while the level of Treg and CD8+ T cells gradually increased. Furthermore, we found a lower percentage of CD3+, CD4+, CD4+/CD8+ and NK cells in association with lymph node metastasis, accompanied by a higher number of CD8+ T cells. Interestingly, after treatment with neoadjuvant chemotherapy, the levels of Tregs, CD3+, CD4+ and CD4+/CD8+ ratio of patients were all upregulated compared with the levels before treatment, indicating the recovery of cytotoxic lymphocytes and a consolidation of the immunosuppressive microenvironment at the same time (P < 0.05). Immune dysfunction is commonly observed in breast cancer patients, which is closely associated with tumor progression and lymph node metastasis. Neoadjuvant chemotherapy was found to highly influence the number of T lymphocytes and improve the immune function of T lymphocyte subsets in breast cancer patients. At the same time, as immunosuppressive cells, the proportion of Tregs (CD4+CD25+CD127lowTreg) also increased after treatment with neoadjuvant chemotherapy. Our results provide guidance for the development of new combination strategies during neoadjuvant chemotherapy to reverse the immunosuppressive microenvironment and achieve better clinical outcomes.

Ferroptosis, a new form of cell death: mechanisms, biology and role in gynecological malignant tumor.

Ferroptosis, a term coined by Dixon et al. in 2012, refers to an iron-dependent form of regulated cell death driven by an overload of lipid peroxides on cellular membranes. It is morphologically and mechanistically distinct from apoptosis and other types of regulated cell death. Many studies have confirmed that ferroptosis is involved in the occurrence and development of many diseases, such as neurodegenerative diseases, chronic cardiovascular diseases, respiratory diseases and even tumors. While in the systemic diseases of obstetrics and gynecology, the related researches are still limited. In this article, we retrieved PubMed and WEB OF SCI databases for articles and reviews published before May 6, 2022, using "ferroptosis, ferroptosis regulator, gynecological tumors" as keywords, and comprehensively reviewed on their basis. Here, we systematically summarize the studies on the mechanism and characteristics of ferroptosis, investigate the role of ferroptosis in clinical systemic diseases of obstetrics and gynecology, evaluate the research status, unsolved problems and further research directions of ferroptosis, so as to let people learn more about ferroptosis and establish a research foundation for the exploration of the treatment strategies for ferroptosis-mediated diseases.

Emerging Bioactive Agent Delivery-Based Regenerative Therapies for Lower Genitourinary Tissues.

Injury to lower genitourinary (GU) tissues, which may result in either infertility and/or organ dysfunctions, threatens the overall health of humans. Bioactive agent-based regenerative therapy is a promising therapeutic method. However, strategies for spatiotemporal delivery of bioactive agents with optimal stability, activity, and tunable delivery for effective sustained disease management are still in need and present challenges. In this review, we present the advancements of the pivotal components in delivery systems, including biomedical innovations, system fabrication methods, and loading strategies, which may improve the performance of delivery systems for better regenerative effects. We also review the most recent developments in the application of these technologies, and the potential for delivery-based regenerative therapies to treat lower GU injuries. Recent progress suggests that the use of advanced strategies have not only made it possible to develop better and more diverse functionalities, but also more precise, and smarter bioactive agent delivery systems for regenerative therapy. Their application in lower GU injury treatment has achieved certain effects in both patients with lower genitourinary injuries and/or in model animals. The continuous evolution of biomaterials and therapeutic agents, advances in three-dimensional printing, as well as emerging techniques all show a promising future for the treatment of lower GU-related disorders and dysfunctions.

Advances in immunotherapy and molecular targeted therapy of gestational trophoblastic tumor: current practice and future perspectives.

Gestational trophoblastic neoplasia (GTN) is a rare pregnancy-related gynecological malignancy caused by abnormal proliferation of placental trophoblastic cells. It can invade the uterine muscle layer and metastasize early, more common in women of childbearing age. GTN is invasive and can destroy surrounding tissues and blood vessels, causing massive bleeding in uterus and metastatic sites (such as lung, liver, brain, etc.) through blood transfer. Chemotherapy is the main treatment for GTN, and the disease is extremely sensitive to chemotherapy and can be cured by chemotherapy. However, in clinical practice, a large number of patients have failed chemotherapy or even multiple treatments due to drug resistance, recurrence or metastasis of special sites. Therefore, how to individually select the initial chemotherapy regimen and reduce the occurrence of drug resistance is the key to the treatment of high-risk GTN. With the remarkable efficacy of immunotherapy in endometrial cancer, cervical cancer and other diseases, the research on GTN has been further deepened. Therefore, this review discusses the mechanism, methods and efficacy of GTN immunotherapy and molecular targeted therapy, in order to provide new ideas for the diagnosis and treatment of GTN.

Tripronuclear Zygotes in IVF Laboratory Quality Control: Experimental Evaluation and Potential Applications.

This study set out to evaluate quality control within a new in vitro fertilization (IVF) laboratory environment and of new incubators based on the culture results of tripronuclear zygotes. The representative environmental indicators within new and old IVF laboratories were monitored, and tripronuclear zygotes were cultured in the two laboratories; the results were analyzed and compared. Subsequently, tripronuclear (3PN) zygotes were cultured in both new and old incubators and the culture results were compared. No differences were found in embryo development between 3PN zygotes in the old and new laboratories. However, in the quality control test, the degeneration rate and developmental arrest rate in the new incubator early phase group were significantly increased when compared with the old incubators. Moreover, the grade I embryo rate also decreased significantly. Nevertheless, all the above comparisons in the new incubator later phase group showed no statistical significance as compared to those observed in old incubators. Tripronuclear zygotes are sensitive to the environment in IVF laboratories and can be considered useful during quality control trials of new IVF laboratories and new equipment including incubators.

The vitrification system may affect preterm and cesarean delivery rates after single vitrified blastocyst transfer.

The purpose of this study was to investigate the possible effects of different vitrification systems on single vitrified blastocyst transfer cycles. The clinical and birth outcomes of 412 patients who underwent single vitrified blastocyst transfer between January 2018 and June 2020 were retrospectively analyzed and compared between patients who underwent blastocyst vitrification with kit A (group A, 196 patients) and those who underwent blastocyst vitrification with kit B (group B, 216 patients). Clinical outcomes, including the clinical pregnancy rate, ongoing pregnancy rate, early miscarriage rate, late miscarriage rate, ectopic pregnancy rate, twin pregnancy rate, and induced labor rate due to fetal malformation, were not significantly different between the two groups (P > 0.05). The preterm delivery rate among singleton newborns (11.57% vs. 3.23%, P < 0.05) and the cesarean delivery rate were significantly higher in group B than in group A (70.25% vs. 57.26%, P < 0.05). Birth outcomes, including the male-to-female ratio, low-birth-weight rate, macrosomia rate, birth defect rate, newborn gestational age, neonatal body weight, and singleton neonatal body length, were not significantly different (P > 0.05). Our findings suggest that different vitrification systems might differentially affect birth outcomes. Such disparity could reflect differences in kit composition and/or protocol.ABBREVIATIONS: DMSO: dimethyl sulfoxide; ES: equilibration solution; VS: vitrification solution; BMI: body mass index; ICSI: intracytoplasmic sperm injection; OR: odds ratio; CI: confidence interval.

Identification of Three Potential circRNA Biomarkers of Polycystic Ovary Syndrome by Bioinformatics Analysis and Validation.

OBJECTIVE: It is well known that circRNAs are closely involved in the progression of various diseases. However, their functions and potential regulatory mechanisms in polycystic ovary syndrome (PCOS) remain largely unknown. In the present study, our aim was to investigate the potential diagnostic value of circRNAs in PCOS. METHODS: The circRNA dataset GSE145296, mRNA dataset GSE155489 and miRNA GSE138572 were downloaded from Gene Expression Omnibus (GEO) database. Then, differentially expressed genes (DEGs) were identified. Based on the potential interactions, a network of cirRNA-related competing endogenous RNAs (ceRNAs) was constructed. Biological functions were predicted by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. For further validation, qRT-PCR method was used to detect the expression level of the candidate circRNAs. Then, receiver operating characteristics (ROC) were constructed to evaluate the diagnostic value of the three differentially expressed circRNA (DE-circRNA). RESULTS: We constructed a network of cirRNA-related ceRNA network. Hsa_circ_0075691, hsa_circ_0075692 and hsa_circ_0085997 were validate to be dysregulated in PCOS. CONCLUSION: Hsa_circ_0075691, hsa_circ_0075692 and hsa_circ_0085997 may be potential diagnostic biomarkers of PCOS, but their specific regulatory mechanisms still need to be further studied.

Genome-wide analysis of gene expression in human embryonic tooth germ.

While numerous genes that play important regulatory roles during tooth development in mice have been identified, little is known about gene expression profile and their function during human odontogenesis. To unveil expression profile of odontogenic genes in humans, we conducted genome-wide gene expression analysis by microarray assays to analyze differential gene expression between tooth germ and lip tissue from 11-week old human fetuses. We identified 167 genes that are strongly expressed in the cap stage tooth germ as compared to the lip tissue. Among them, 145 genes were further identified by gene ontology enrichment analysis that are highly represented in multiple gene ontology classes, include extracellular components, sequence-specific DNA binding proteins, Wnt-protein binding molecules, system development, organogenesis, and cell differentiation. Sixty-seven genes that are known to be associated with mammalian tooth development and tooth abnormalities were identified. Real-time PCR was further employed to validate microarray data. Moreover, in situ hybridization assay demonstrated tooth type specific expression of ISL1 and BARX1 in the incisor, canine, and molar respectively, consistent with microarray results. Our results represent a set of reliable data that could provide a solid base for future elaboration of molecular mechanisms underlying human tooth development.