Endometritis is a common inflammatory disorder of the female reproductive tract caused by microbial infection or immune dysregulation that impairs endometrial function and reproductive outcomes. Growing evidence indicates that programmed cell death (PCD), particularly pyroptosis, plays a pivotal role in the pathophysiology of endometritis. Pyroptosis links cell death to inflammatory signaling through inflammasome activation and gasdermin (GSDM)-mediated membrane perforation. The canonical NLRP3-caspase-1-GSDMD axis, the noncanonical caspase-4/5/11-GSDMD pathway, and caspase-3-GSDME-dependent pyroptosis-like death all have been implicated in amplifying endometrial inflammation. Experimental and clinical studies demonstrate the upregulation of NLRP3, caspase-1, and GSDMD in affected endometrial tissues, supporting their pathological relevance. Upstream mechanisms, including the high-mobility group box 1 (HMGB1)-TLR 4 axis, PI3K-AKT signaling, and microRNA (miRNA)-mediated modulation, further regulate the pyroptotic response. These insights highlight therapeutic opportunities, including pharmacological inhibitors, miRNA-based interventions, and antioxidant strategies. Nevertheless, most evidence derives from preclinical studies, and translational validation in patients remains limited. This review presents an integrated molecular framework and candidate therapeutic targets to support diagnostic stratification and precision interventions that optimize reproductive outcomes.

BACKGROUND:The cytokines interleukin (IL)-6 and transforming growth factor-beta (TGF-β) are established inducers of pathogenic T helper 17 (Th17) cells from naïve T cells. In the maternal-fetal compartment, IL-6 signaling elevates levels of indoleamine 2,3-dioxygenase 1 (IDO1). This study investigated whether IL-6 regulates Th17 cytokine production through IDO1. METHODS:Human decidua and chorionic villi (HDCV) were collected from normal early pregnant women undergoing elective termination. For HDCV culture, explants were treated with increasing doses of IL-6 (0-50 ng/mL) or co-treated with IL-6 and the IDO1 inhibitor 1-methyltryptophan (1-MT) for 24 h. HDCV were also treated with IL-6 (5 ng/mL) alone or in combination with TGF-β (0.01-0.1 ng/mL) for 24 h. Recurrent pregnancy loss (RPL) mice were intraperitoneally injected with IL-6 (2, 10, or 50 ng/mL), alone or combined with 1-MT and/or Cosentyx, from gestational day (GD) 0.5 to 8. Protein expression levels of IL-6, IDO1, IL-17, and IL-22 were assessed by Western blotting and immunohistochemistry. Embryo absorption rate (EAR) was calculated on GD 12.5. Cytokine concentrations in supernatants or serum were measured using enzyme-linked immunosorbent assay. RESULTS:In HDCV tissues, IL-6 positively correlated with IDO1 and negatively correlated with IL-17/IL-22. Exogenous IL-6 dose-dependently upregulated IDO1 and suppressed IL-17/IL-22 in cultured explants, effects reversed by 1-MT. Physiological TGF-β1 (0.01-0.1 ng/mL) enhanced IL-6-induced IDO1 upregulation and Th17 cytokine suppression. In RPL mice, IL-6 reduced EAR and placental IL-17/IL-22 expression while increasing IDO1; these effects were blocked by 1-MT and restored by Cosentyx. CONCLUSIONS:During normal pregnancy, IL-6 alone or the combination of IL-6 and TGF-β at the maternal-fetal interface may inhibit Th17 cytokine production by upregulating IDO1 expression, thereby maintaining pregnancy stability.

Background: Antithyroid antibodies(ATAb),especially thyroid peroxidase antibodies (TPOAb), have been found to be related to recurrent pregnancy loss (RPL),but this relationship mainly focus on the patients before pregnancy. The aim of this study was to evaluate the association of ATAb with RPL before and during Pregnancy. Materials and Methods: The clinical data of women with RPL or with spontaneous pregnancy loss (SPL), who met inclusion criteria were registered from January 2017 to January 2024, were retrospectively analyzed. The presence of ATAb with times of SPL, the changes of ATAb before pregnancy and during in 19 to 28 weeks of gestation（19-28 WG） were noted. Results: In 19-28 WG, among the patients with 0, 1 and ≥2 times of SPL,and among TGAb positive patients with 0, 1 and ≥2 times of SPL, the TGAb concentrations were the highest in patients with ≥2 times of SPL ( P = 0.001 and 0.044), the TGAb concentrations in patients with 1 and ≥2 times of SPLwere significantly higher than that in patients with 0 time of SPL(P =0.0004 and 0.001; P =0.022 and 0.024). Before pregnancy, in patients with 1 and ≥2 times of SPL, the TGAb concentration were significantly lower(P =0.01 and 0.012), the TPOAb concentration were significantly higher(P =0.001 and 9.6E-7) than that in 19-28WG; in TGAb negative patients with 1 time of SPL,TGAb concentration were significantly lower(P =0.031) than that in 19-28WG;in ATAb , TGAb and TPOAb negative patients with ≥2 times of SPL,the concentration of TPOAb were significantly lower(P =0.002, 0.007 and 0.0004) than that in 19-28WG. Conclusions: In midtrimester of pregnancy,TGAb concentration increase,while TPOAb decrease, the association of TPOAb with SPL may become less obvious, but the association of TGAb with SPL may be much obvious, especially with ATAb, TGAb and TPOAb negative patients, TGAb may be a biomarker of pregnant women with history of RPL.

Poor ovarian response (POR) constitutes a notable clinical challenge within the domain of assisted reproductive technology, primarily attributable to the lack of reliable biomarkers for precise diagnosis and treatment. This study reveals significantly reduced levels of insulin-like growth factor 1 (IGF-1) in the serum, follicular fluid (FF), and granulosa cells (GCs) of patients with POR in comparison to those exhibiting a normal ovarian response (NOR). Notably, FF IGF-1 concentrations demonstrated significant positive correlations with crucial IVF outcomes, including the numbers of metaphase II (MII) oocytes, 2-pronuclear zygotes, and high-quality embryos. To establish causality, we employed complementary in vivo models: systemic insulin-like growth factor binding protein acid labile subunit (Igfals) knockout mice and granulosa cell specific IGF-1 receptor (Igf-1r) knockout mice. These models collectively demonstrated that disruption of the IGF-1 signaling axis impairs follicle-stimulating hormone (FSH) responsiveness and arrests follicular development at the secondary stage, thereby recapitulating the core POR phenotype. Building on these mechanistic insights, we developed novel clinical prediction tools based on FF IGF-1: a POR risk model [Area under the curve (AUC) = 0.914] and a pregnancy outcome nomogram (AUC = 0.893), both of which significantly outperform traditional ovarian reserve parameters (such as anti-Müllerian hormone and antral follicle count). Decision curve analysis (DCA) further validated a substantial clinical net benefit. This study aids clinicians in the early identification of patients with POR and provides a theoretical foundation for timely intervention and adjustment of treatment strategies.

IntroductionPolycystic ovary syndrome (PCOS) is one of the most common endocrine and metabolic disorders affecting women of reproductive age. Dendrobium officinale polysaccharides (DOP) have shown multiple pharmacological activities, but their therapeutic effects and underlying mechanisms in PCOS remain incompletely understood.MethodsA dehydroepiandrosterone (DHEA)-induced mouse model of PCOS was established to evaluate the effects of DOP. Estrous cyclicity, ovarian histopathology, serum hormone levels, RT-qPCR, and Western blot analyses were performed to assess reproductive function, endocrine changes, and MAPK/ERK-related signaling.ResultsDOP treatment restored estrous cyclicity, improved ovarian morphology, and partially normalized serum luteinizing hormone, follicle-stimulating hormone, and testosterone levels. In addition, DOP reduced ERK1/2 phosphorylation and downregulated the expression of CYP17A1 and CYP19A1.ConclusionDOP ameliorated reproductive and endocrine abnormalities in a DHEA-induced mouse model of PCOS. The findings suggest that modulation of MAPK/ERK signaling may contribute to the biological effects of DOP, although further mechanistic studies are required to establish causal relationships.

Objective To examine the association between the percentage of peripheral natural killer cells and thyroid autoimmunity in women with a history of miscarriage and assess whether B-cells mediate this association. Methods This retrospective cross-sectional study was conducted on 927 women with a history of miscarriage treated at the Affiliated Hospital of Guizhou Medical University (2021–2023). Peripheral T-cell, B-cell, and natural killer cell subsets and thyroid antibodies were assessed. Multivariable logistic regression, restricted cubic splines, and mediation analyses were performed. Results Women with thyroid autoimmunity had lower percentage of peripheral natural killer cells and higher percentage of B-cells than those without thyroid autoimmunity (both p < 0.001). The percentage of peripheral natural killer cells demonstrated a consistent inverse association with thyroid autoimmunity after adjustment (adjusted odds ratios: 0.00; 95% confidence interval: 0.00–0.02; all p < 0.001). Restricted cubic spline analysis indicated a nonlinear dose–response relationship that was stronger in women aged ≥35 years and in those without recurrent miscarriages. B-cells partially mediated the association between the percentage of peripheral natural killer cells and thyroid autoimmunity (31.4% of the total effect; ab = −0.166; p < 0.001). Conclusion Lower percentage of peripheral natural killer cells is linked to higher odds of thyroid autoimmunity in women with a history of miscarriage, and B-cells partly explain this relationship, supporting the use of peripheral immune profiling to identify thyroid autoimmunity risk.

Breast cancer brain metastasis (BCBM) is a major cause of poor prognosis in breast cancer, driven by complex molecular mechanisms. Innovative diagnostic and therapeutic strategies are urgently needed. We integrated single-cell RNA sequencing, multiomics profiling from the TCGA database, and machine learning to explore the molecular features of BCBM. Cell composition, gene expression, and subtypes were characterized. Prognostic models were developed, and potential drug targets were computationally identified through analysis of differentially expressed genes and molecular interactions. Experimental validation of these targets was performed using orthotopic implantation of MDA-MB-231-Luc cells in nude mice. scRNA-seq revealed 10 cell types and 1,479 differentially expressed genes, highlighting significant differences between the primary brain cancer and BCBM. Multiomics clustering defined two distinct subtypes (CS1 and CS2) with differential prognosis. A CoxBoost + RSF model identified hub genes (BTG2, PSMB8, SRGN, HLA-DPB1) and demonstrated high predictive accuracy for 3-, 5-, and 10-year survival (AUCs: 0.813, 0.788, and 0.776, respectively). Drug sensitivity analysis highlighted five candidate agents, with molecular docking confirming strong binding affinity to targeted proteins. In vivo experiments confirmed that PSMB8 and HLA-DPB1 promoted brain metastasis, while BTG2 and SRGN suppressed it. High-risk patients exhibited elevated monocyte proportions, which were involved in intercellular interactions. This study delineates the molecular landscape of BCBM, establishes robust prognostic models, and identifies promising therapeutic targets, offering a framework for precision diagnosis and individualized treatment.

This study investigates the impact of the CD2-CD58 signaling axis on effector T cell function and tumor metabolic crosstalk in breast cancer brain metastasis (BCBM) using single-cell transcriptomic analysis. scRNA-seq data analysis revealed the critical role of CD2-CD58 signaling between CD8+ T cells and tumor cells in BCBM. Functional assays demonstrated that CD2 knockdown inhibited cytotoxic T lymphocyte (CTL) proliferation, activation, and cytotoxicity, leading to impaired tumor cell recognition and enhanced proliferation, migration, and invasion. In vivo studies showed that CD2-deficient CTLs promoted tumor growth and brain metastasis while affecting metabolic reprogramming by altering key enzyme expressions in pyrimidine biosynthesis and arginine metabolism pathways. The findings suggest that CD2 enhances CTL function against tumor cells and influences their metabolic states, highlighting the role of CD2 in remodeling the brain metastatic microenvironment in breast cancer.

Background: Premature ovarian insufficiency (POI) is the loss of ovarian function among women <40 years of age, and immune disorders play a critical role in POI development. Indoleamine 2,3-dioxygenase (IDO) catalyses tryptophan metabolism via the kynurenine pathway and plays a key role in preventing and treating immune-related diseases. Methods: Human ovarian granulosa cells (hGCs) were collected via the density gradient method, pZP3 was used to establish an immune POI mouse model, and an AAV vector carrying IDO1 (IDO-AAV) was injected into mouse ovaries to induce IDO overexpression. Ovarian function was measured by the oestrous cycle, serum AMH concentration, degree of ovarian fibrosis and number of follicles. Findings: IDO protein levels and mRNA expression in hGCs were lower in the POI group than in the control group (P < 0.05). Both the ovarian function and IDO levels in the POI + Water group and the POI + Glu group were significantly lower than those in the control group. In POI model mice injected with IDO-AAV, ovarian function and the CD4 + CD25 + Foxp3+ regulatory T (Treg) cell proportion were increased compared with those in mice injected with the natural control AAV. The FoxP3 mRNA expression level in Treg cells was positively correlated with the IDO mRNA expression level, whereas the RORγt mRNA expression level in Th17 cells was negatively correlated with the IDO mRNA expression level, further suggesting that IDO may be related to Treg and Th17 cells through AhR and subsequently regulate immunity and ovarian function. Conclusion: Increasing ovarian IDO levels in POI mice improved ovarian function.

PURPOSE: Breast cancer brain metastasis (BCBM) is a major clinical challenge due to the blood-brain barrier (BBB) restricting effective drug delivery, resulting in limited therapeutic options and poor prognosis. This study aims to develop ANG peptide-modified exosomes loaded with oleanolic acid (ANG-Exo-OA) to enhance brain-targeted delivery and investigate its anti-tumor mechanisms through GPX4-mediated ferroptosis in BCBM treatment. METHODS: Oleanolic acid was encapsulated into mesenchymal stem cell-derived exosomes via electroporation, with ANG peptide conjugated using thiol-maleimide chemistry. ANG-Exo-OA was characterized using nanoparticle tracking analysis, transmission electron microscopy, and Western blot. Biocompatibility was evaluated via cytotoxicity assays, hematoxylin and eosin staining, and serum biochemistry. Brain-targeting efficiency was assessed using an in vitro BBB model and in vivo imaging. Anti-tumor effects and GPX4 pathway involvement were examined in a Luc-labeled MDA-MB-231 BCBM mouse model using Western blot, malondialdehyde, glutathione assays, and GPX4 overexpression rescue experiments. Statistical analyses included t-tests and ANOVA. RESULTS: ANG-Exo-OA exhibited excellent biocompatibility, stability, and enhanced BBB penetration, with significant brain accumulation. It suppressed MDA-MB-231 cell proliferation, migration, and induced apoptosis, accompanied by decreased GPX4 expression and increased lipid peroxidation. In vivo, ANG-Exo-OA reduced tumor growth and promoted ferroptosis, effects reversed by GPX4 overexpression. CONCLUSION: ANG-Exo-OA represents a promising therapeutic strategy for BCBM, achieving enhanced brain-targeted delivery and effective GPX4-mediated ferroptosis induction in a TNBC model. While the findings highlight its potential value for BCBM treatment, further studies involving additional breast cancer subtypes and more clinically relevant models are required to determine its broader applicability.

Objective:To determine the relationship between physical activity (PA) patterns and infertility among women in the United States and to ascertain whether glycated hemoglobin (HbA1c) influences this association. Design:A cross-sectional study of PA patterns and infertility was conducted. The PA classification was based on two categories: recreational PA and work-related PA. The subgroups were classified as inactive, less active, or active. We conducted data analysis via both multiple logistic regression analysis and mediation analysis. Setting:National Health and Nutrition Examination Survey (NHANES, 2013-2018). Participants:Women aged 18-49 years (n, 3,948). Results:There was no statistically significant link demonstrated between infertility and work-related PA patterns. The recreational PA group may decrease the prevalence of infertility, with its occurrence being merely 0.79 times that of inactive group. (95% CI: 0.62, 1.0; p = 0.045). The consistency of this discrepancy was not preserved in Model III after the mixed effect was incorporated into the recreational PA group. The stratified research findings revealed that the association between recreational PA patterns and infertility was influenced by variables such as age, BMI, and history of diabetes. Furthermore, the mediation analysis revealed that recreational PA did not have a statistically significant direct effect on infertility (p = 0.098). HbA1c serves as a mediator in this interaction (95% CI: -0.06, -0.02). Conclusion:Recreational PA patterns were associated with infertility among women aged 18-49 years in the United States, which was likely due to the effects of HbA1c.

Background: The immunologic factors are the chief reason for recurrent pregnancy loss (RPL) and induction ofmaternal-fetal tolerance is the main treatment for this cause of RPL, but the effect of this method is uncertainly andneeds multiple doses and/or interventions. The aim of this study was to investigate whether a single administrationof transforming growth factor-β1 (TGF-β1) can improve the pregnancy outcomes of RPL mice and whether theimprovement is cause by TGF-β1 driving the expression of immune tolerance molecule indoleamine 2,3-dioxygenase(IDO).Materials and Methods: In this experimental study, 40 RPL model mice were equally divided into a control group,that received 0.01 M phosphate-buffered saline (PBS), and a treatment group, that received PBS containing 2, 20, and200 ng/ml TGF-β1 via tail vein injection. The mice were sacrificed at 13.5 days of pregnancy and the embryo resorptionrate was determined. The expression of IDO, TGF-β1, and TGF-β3 were detected in the placenta using westernblotting and immunohistochemistry techniques.Results: The expression of IDO was positively correlated with TGF-β1 in the placental tissue of RPL mice (r=0.591,P<0.001). In all treatment groups, the embryo resorption rates were significantly lower than the control group andthe expression of IDO in the placental tissue of all treatment groups was significantly higher than the control group.The expression of TGF-β1 increased gradually from, 2, 20 to 200 ng/ml in treatment groups, and the concentrationof exogenous TGF-β1 positively correlated with the expression of TGF-β1, in placental tissues in treatment groups(r=0.372, P=0.018).Conclusion: Exogenous TGF-β1 improves pregnancy outcomes in RPL mice, and the possible therapeutic mechanismis that exogenous TGF-β1 induces the persistent expression of endogenous TGF-β1 and IDO due to mutuallyinduced expression of the other. This experiment may provide a new direction and idea for the future treatment ofRPL patients.

Objective This study aims to explore the role of exosome-related genes in breast cancer (BRCA) metastasis by integrating RNA-seq and single-cell RNA-seq (scRNA-seq) data from BRCA samples and to develop a reliable prognostic model.Methods Initially, a comprehensive analysis was conducted on exosome-related genes from the BRCA cohort in The Cancer Genome Atlas (TCGA) database. Three prognostic genes (JUP, CAPZA1 and ARVCF) were identified through univariate Cox regression and Lasso-Cox regression analyses, and a metastasis-related risk score model was established based on these genes. Immune cell infiltration, immune escape and drug sensitivity disparities between high- and low-risk groups were assessed using CIBERSORT and single-sample gene set enrichment analysis (ssGSEA) methods. High- and low-risk cell populations were discerned based on the expression of prognostic genes in BRCA scRNA-seq data.Results M0 and M1 macrophages significantly promote the metastasis of breast cancer (BRCA). The developed prognostic model demonstrates good predictive performance for patient survival at 1, 3 and 5 years, with AUC values of 0.654, 0.602 and 0.635, respectively. Compared to the low-risk group, the high-risk group exhibits increased immune cell infiltration and higher levels of immune evasion. scRNA-seq data reveal that high-risk cells have significantly higher risk scores and exhibit notable differences in signalling pathways and intercellular communication patterns.Conclusions This study presents a novel risk score model based on exosome-related genes, validated by comprehensive analyses including differential expression, survival analysis and external dataset validation. The model’s clinical significance is reinforced through its ability to stratify patients into high- and low-risk groups with distinct survival outcomes and immune landscape characteristics. The integration of RNA-seq and scRNA-seq data highlights the predictive accuracy of the model and underscores its potential for identifying novel therapeutic targets and improving patient prognosis.

Premature ovarian insufficiency (POI) severely impacts women’s reproductive and overall health, yet effective treatments remain elusive. Research on its pathogenic mechanisms and therapeutic strategies is therefore critical. Due to the scarcity of ovarian samples from POI patients, animal models have become indispensable tools for investigation. Notably, immune-related POI accounts for an increasing proportion of cases, with over half of idiopathic POI cases hypothesized to involve immune dysregulation. Consequently, immune-mediated POI animal models are widely used to study immune-related mechanisms. This article compares the advantages, limitations, and applications of various immune-related POI animal models, aiming to guide researchers in selecting the most appropriate model for their specific research goals and experimental designs.

INTRODUCTION:Accumulating evidence suggests the association between abnormal angiogenesis at the maternal-fetal interface and recurrent pregnancy loss (RPL); nonetheless, the mechanism remains largely unknown. Previous studies have reported the clinical effect of the traditional Chinese medicine Danshen in the treatment of RPL. This study aimed to investigate whether salvianolic acid B (SalB), the primary water-soluble component of Danshen, could reduce the embryonic absorption rate (EAR) by increasing placental and decidual angiogenesis in RPL mice and to explore the possible mechanism. METHODS:The decidual and chorionic tissues were collected from normal pregnancies and unknown recurrent pregnancy loss (URPL) patients. Western blotting was used to determine the expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α (HIF-1α) in the tissues. Different doses of SalB and/or the VEGF inhibitor PTC299 were intragastrically administered to normal and RPL pregnant mice daily at 0.5 day of pregnancy for 10 days. The EAR, mean placental weight (MPW), and micro vessel density (MVD) were determined in placental and decidual tissues, and the number of live pups per litter was counted. The expression of VEGF and HIF-1α in the tissues was evaluated using western blotting and immunohistochemistry. RESULTS:The VEGF protein levels in decidual and chorionic tissues were significantly lower, and HIF-1α levels were significantly higher than that of normal pregnancies. The EAR was significantly higher, MVD, MPW, and protein levels of VEGF in the placental and decidual tissues of RPL mice were significantly lower than those in normal mice. In contrast, the protein levels of HIF-1α were significantly higher in RPL mice than in normal mice. SalB restored the morphological changes in the uterus of RPL mice, as well as the number of blood vessels in the placenta and decidua, and ameliorated adverse embryonic development in mice (such as neural tube defects and reduced crown-rump length), thereby increasing the pups per. Additionally, SalB increased the VEGF/VEGFR2/p-VEGFR2 levels, placental and decidual MVD, and MPW and decreased the HIF-1α levels and EAR in a dose-dependent manner. A positive association of daily SalB dose (0-100 mg/kg) with the VEGF levels, placental and decidual MVD and MPW, and a negative association of daily SalB dose with the HIF-1α levels and EAR were observed.PTC299 reversed the aforementioned increases and decreases in the daily SalB intake of RPL mice. Among these, the daily dose of 100 mg/kg of SalB was deemed optimal, and a daily dose of SalB exceeding 100 mg/kg did not entirely induce these changes. No correlation between HIF-1α and VEGF was observed in decidual and placental/ chorionic tissues from normal pregnancies and URPL patients, and from normal and RPL mice, but a negative correlation between the two factors was observed in the tissues from RPL mice in the presence of SalB with or without PTC299. CONCLUSIONS:SalB ameliorates RPL by restoring physiological HIF-1α/VEGF balance and placental angiogenesis. Optimal daily dose was 100 mg/kg, which demonstrated the absence of embryotoxicity or mitigated the embryotoxicity of RPL mice, while higher doses (400 mg/kg) showed lesser improvement and increased hepatotoxicity. The promotion of placental and decidual angiogenesis may be an effective strategy for treating unexplained RPL.

This study aims to investigate the role of C-C Motif Chemokine Ligand 18 (CCL18) in glioblastoma multiforme tissues. Glioblastoma multiforme-related gene expression, clinical parameters, and the corresponding expression data in normal tissues were obtained from The Cancer Genome Atlas database and The Genotype-Tissue Expression database, respectively. The expression levels of CCL18 in 1157 normal tissues, 166 glioblastoma multiforme tissues and its relationship with clinicopathological features were analyzed. The degree of immune infiltration in glioblastoma multiforme tissues was assessed using single sample gene set enrichment analysis algorithm and ESTIMATE algorithm. Gene set enrichment analysis was used to explore the biological processes and pathways that may be regulated by CCL18. Univariate and multivariate Cox regression analysis were used to predict the risk factors affecting the prognosis of glioblastoma multiforme patients. Based on risk factors, nomogram models were constructed. Besides, the expression and roles of CCL18 in glioblastoma multiforme were validated in Clinical Proteomic Tumor Analysis Consortium database, GSE57872 dataset, and in vitro. CCL18 mRNA and protein are highly expressed in glioblastoma multiforme tissues and are closely associated with immune infiltration and prognosis in glioblastoma multiforme patients. CCL18 is involved in regulating multiple neural-, immune-, and tumor-related signaling pathways, and potentially promote proliferation, angiogenesis, migration, and epithelial-mesenchymal transition in glioblastoma multiforme tissues. Moreover, CCL18 promoted cell viability and migration in vitro. CCL18 might be a potential molecular marker for prognosis prediction and targeted therapy in glioblastoma multiforme patients.

BACKGROUND:Premature ovarian insufficiency (POI) is the loss of ovarian function among women <40 years of age, and immune disorders play a critical role in POI development. Indoleamine 2,3-dioxygenase (IDO) catalyzes tryptophan metabolism via the kynurenine pathway and plays a key role in preventing and treating immune-related diseases. METHODS:Human ovarian granulosa cells (hGCs) were collected via the density gradient method, zona pellucida protein 3 was used to establish an immune POI mouse model, and an adeno-associated virus (AAV) vector carrying IDO1 (IDO-AAV) was injected into mouse ovaries to induce IDO overexpression. Ovarian function was measured by the estrous cycle, serum anti-Müllerian hormone concentration, degree of ovarian fibrosis, and number of follicles. FINDINGS:IDO protein levels and mRNA expression in hGCs were lower in the POI group than in the control group (P < 0.05). Both the ovarian function and IDO levels in the POI + Water group and the POI + Glu group were significantly lower than those in the control group. In POI model mice injected with IDO-AAV, ovarian function, and the CD4+ CD25+ Foxp3+ regulatory T (Treg) cell proportion were increased compared with those in mice injected with the natural control AAV. The FoxP3 mRNA expression level in Treg cells was positively correlated with the IDO mRNA expression level, whereas the RORγt mRNA expression level in Th17 cells was negatively correlated with the IDO mRNA expression level, further suggesting that IDO may be related to Treg and Th17 cells through AhR and subsequently regulate immunity and ovarian function. CONCLUSION:Increasing ovarian IDO levels in POI mice improved ovarian function.

Preimplantation genetic testing for monogenic diseases (PGT-M) can be used to select embryos that do not develop disease phenotypes or carry disease-causing genes for implantation into the mother’s uterus, to block disease transmission to the offspring, and to increase the birth rate of healthy newborns. However, the traditional PGT-M technique has some limitations, such as its time consumption, experimental procedural complexity, and the need for a complete family or reference embryo to construct the haplotype. In this study, proband-independent haplotyping based on NGS-based long-read sequencing (Phbol-seq) was used to effectively construct haplotypes. By targeting the mutation sites of single gene disease point mutations and small fragment deletion carriers, embryos carrying parental disease-causing mutations were successfully identified by linkage analysis. The efficiency of embryo resolution was then verified by classical Sanger sequencing, and it was confirmed that the construction of haplotype and SNP linkage analysis by Phbol-seq could accurately and effectively detect whether embryos carried parental pathogenic mutations. After the embryos confirmed to be nonpathogenic by Phbol-seq-based PGT-M and confirmed to have normal copy number variation by Phbol-seq-based PGT-A were transplanted into the uterus, gene detection in amniotic fluid of the implanted embryos was performed, and the results confirmed that Phbol-seq technology could accurately distinguish normal genotype embryos from genetically modified carrier embryos. Our results suggest that Phbol-seq is an effective strategy for accurately locating mutation sites and accurately distinguishing between embryos that inherit disease-causing genes and normal embryos that do not. This is critical for Phbol-seq-based PGT-M and could help more single-gene disease carriers with incomplete families, de novo mutations or suspected germline mosaicism to have healthy babies with normal phenotypes. It also helps to reduce the transmission of monogenic genetic diseases in the population.

Abstract Backgrouds: What is the effect of low-molecular-weight heparin on twin pregnancies with increased D2 dimer following assisted reproductive technology（ART）? Methods: A retrospective cohort study. The study explored data from twin pregnancies with increased D2 dimer levels following ART who underwent foetal protection treatment at the reproductive centre of the Affiliated Hospital of Guizhou Medical University from March 2017 to December 2019. The main outcomes examined were the abortion rate of twins and the twin rate in the third trimester. Results: Twin pregnancies exhibited a lower median age and higher D2-dimer levels than single pregnancies. 400 twin pregnancies had increased D2-dimer levels. The median D2 dimer level was 1.38 ug/mL. 258 of the 400 patients received heparin medication. A multivariate analysis of each patient's pregnancy outcomes was used . The twin miscarriage rate treated with heparin was reduced by 48.3% compared to untreated pregnancies, the twin rate in the third trimester increased by 69.8%. There were no differences in twin miscarriage rate or twin rate in the third trimester of twin pregnancies between whole-course medication and early medication in the subgroup. However, there was a decrease in the NICU rate and the incidence of gestational hypertension. Conclusions: Low-molecular-weight heparin could improve the clinical outcomes of twin pregnancies following ART. Patients who undergo full therapy may see superior outcomes in comparison to those who choose early intervention.

The objective of this study is to explore the functions and mechanisms of the LncRNA-KCNQ1OT1/miR-29a-3p/SOCS3 molecular pathway in the context of unexplained recurrent spontaneous abortion (URSA).