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Although the relationship between vaginal microorganisms and fertility has been well established, only few studies have investigated vaginal microorganisms in women undergoing in vitro fertilization (IVF). Our aim was to study the differences in vaginal microbiota between infertile women with repeated implantation failure (RIF) and those who achieved clinical pregnancy in their first frozen embryo transfer cycle. We compared the vaginal microbiota of patients with a history of RIF (n = 37) with that of the control group (n = 43). Following DNA extraction, metagenomic sequencing was employed for the analysis of alpha and beta diversities, distinctions in bacterial species, and the functional annotation of microbial genes. Furthermore, disparities between the two groups were revealed. Alpha diversity analysis revealed that the Shannon index was higher in the RIF group (P < 0.05). There were differences in the beta diversity between groups (P = 0.16). At the bacterial family level, the relative abundance of Actinomycetaceae (P = 0.013) and Ruminococcaceae (P = 0.013) were significantly higher in the RIF group. At the genus level, the abundances of Actinomyces (P = 0.028) and Subdoligranulum (P = 0.013) were significantly higher in the RIF group. At the species level, the abundances of Prevotella timonensis (P = 0.028), Lactobacillus jensenii (P = 0.049), and Subdoligranulum (P = 0.013) were significantly higher in the RIF group. Significant differences in family, genus, species, alpha and beta diversity were observed in the vaginal microbiota between groups. Notably, among these findings, the Subdoligranulum genus emerged as the most prominent correlating factor.
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Background: Previous studies link overweight/obesity to reduced fertility, highlighting weight intervention as vital for better pregnancy outcomes. However, clarity on the role and efficacy of weight loss in enhancing pregnancy is inconsistent. Objective: This study aimed to assess the impact of individualized weight intervention on pregnancy among Chinese overweight/obese infertile women and explore body composition indexes influencing pregnancy outcomes. Methods: This retrospective study involved 363 overweight/obese infertile women admitted to the First Affiliated Hospital of Guangxi Medical University, Guangxi, China, from June 2017 to November 2020. Among them, 249 received personalized weight intervention (intervention group), while 114 did not (control group). Pregnancy outcomes were compared between the two groups, and changes in body composition before and after intervention were measured. Multivariate logistic regression was employed to analyze factors influencing pregnancy outcomes. Results: The intervention group exhibited significantly higher clinical pregnancy rates, natural pregnancy rates, assisted reproductive pregnancy rates, and induced ovulation (IO) pregnancy rates compared to the control group (all P < .05). Following weight intervention, there were significant decreases in body weight, body mass index (BMI), visceral fat area, and body fat (all P < .01). Logistic regression analysis identified polycystic ovary syndrome as the reason for infertility (OR=3.446, P = .016), ∆body weight %≥10% (OR=2.931, P = .014), and ∆visceral fat area% (OR=1.025, P = .047) as positive factors for a successful pregnancy. Conversely, age≥35 years old (OR=0.337, P = .001), BMI≥25 kg/m2 after intervention (OR=0.279, P < .001), and visceral fat area≥100 cm2 after intervention (OR=0.287, P = .007) were identified as negative factors. Conclusions: Individualized weight management enhances pregnancy outcomes in overweight/obese infertile women. Achieving a reduction in body weight by 10% or more, combined with effective control of visceral fat, proves important in improving pregnancy outcomes. Excess visceral fat emerges as an adverse factor impacting successful pregnancy.
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PURPOSE: The purpose of this study is to investigate the function of miR-150-5p in URSA. METHOD: Twenty-six chorionic villous tissues were collected to examine the expression of miR-150-5p and VEGFA by using quantitative polymerase chain reaction (qPCR) and western blot assay, respectively. Transwell assay was conducted to assess the migration and invasion ability of trophoblast cells. The dual-luciferase reporter assay was applied to determine the relationship between miR-150-5p and VEGFA in vitro. Relevant signaling pathway protein expression level was measured via western blot assay. Signaling transduction inhibitor LY294002 was used to block PI3K/AKT/mTOR signaling pathway. Finally, in vivo the effect of miR-150-5p on embryonic absorption rate was evaluated in mice. RESULTS: Clinical samples revealed that miR-150-5p expression was significantly elevated in the villous tissues and serum of URSA patients. Moreover, the overexpressing of miR-150-5p could inhibit both HTR-8/SVneo cell and JAR cell migration, invasion, and restrained PI3K/AKT/mTOR signaling pathway by targeting VEGFA in vitro. This inhibitory effect of miR-150-5p could be reversed by overexpressing the gene of vascular epithelial growth factor A (VEGFA). In contrary, inhibition of miR-150-5p significantly enhanced migration, invasion ability of both HTR-8/SVneo and JAR cells, and also could stimulate PI3K/AKT/mTOR signaling pathway. This promoting effect of miR-150-5p could be ameliorated by LY294002 (PI3K inhibitor). Finally, after miR-150-5p overexpression in vivo, the embryo resorption rate in pregnant mice was increased significantly. CONCLUSIONS: Overall, these findings imply that miR-150-5p is among the key factors that regulate the pathogenesis of URSA.
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Aborto Espontáneo , MicroARNs , Animales , Femenino , Humanos , Ratones , Embarazo , Proliferación Celular , MicroARNs/genética , MicroARNs/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Transducción de Señal/genética , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/metabolismo , Factor A de Crecimiento Endotelial Vascular/genéticaRESUMEN
LAMB3, a major extracellular matrix and basal membrane component, is involved in wound healing. We aimed to understand its role in Asherman's syndrome (AS), which is associated with infertility, by using bioinformatics analysis and cultured endometrial stromal cells (ESCs). MRNAs extracted from tissues obtained from control subjects and patients with severe intrauterine adhesion were sequenced and subjected to bioinformatics analysis and the RhoA/ROCK1/MYL9 pathway was implicated and this subsequently studied using cultured primary ESCs. The effects of overexpression and knockdown and activation and inhibition of LAMB3 on the mesenchymal to myofibroblastic phenotypic transformation of ECCs were assessed using PCR and western blot analysis. Phalloidin was used to localize the actin cytoskeletal proteins. Silencing of LAMB3 reversed the TGF-ß-induced ESC myofibroblast phenotype conversion, whereas overexpression of LAMB3 promoted this process. Activation and silencing of LAMB3 led to remodeling of the ESC cytoskeleton. Overexpression and silencing of LAMB3 caused activation and inhibition of ESCs, respectively. Y-27632 and LPA reversed the activation and inhibition of the RhoA/ROCK1/MYL9 pathway after overexpression and silencing, respectively. These results suggest that LAMB3 can regulate ESC fibrosis transformation and cytoskeleton remodeling via the RhoA/ROCK1/MYL9 pathway. This study provides a potential new target for gene therapy and drug intervention of AS.
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Citoesqueleto , Quinasas Asociadas a rho , Humanos , Quinasas Asociadas a rho/genética , Quinasas Asociadas a rho/metabolismo , Actinas/metabolismo , Proteína de Unión al GTP rhoA/genética , Proteína de Unión al GTP rhoA/metabolismo , Transducción de Señal , Células del Estroma/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Cadenas Ligeras de Miosina/metabolismoRESUMEN
Premature ovarian insufficiency (POI) is a reproductive endocrine disorder characterized by infertility and perimenopausal syndrome, with a highly heterogeneous genetic etiology and its mechanism is not fully understood. Therefore, we utilized Oxford Nanopore Technology (ONT) for the first time to characterize the full-length transcript profile, and revealed biomarkers, pathway and molecular mechanisms for POI by bioinformatics analysis and machine learning. Ultimately, we identified 272 differentially expressed genes, 858 core genes, and 25 hub genes by analysis of differential expression, gene set enrichment, and protein-protein interactions. Seven candidate genes were identified based on the intersection features of the random forest and Boruta algorithm. qRT-PCR results indicated that COX5A, UQCRFS1, LCK, RPS2 and EIF5A exhibited consistent expression trends with sequencing data and have potential as biomarkers. Additionally, GSEA analysis revealed that the pathophysiology of POI is closely associated with inhibition of the PI3K-AKT pathway, oxidative phosphorylation and DNA damage repair, as well as activation of inflammatory and apoptotic pathways. Furthermore, we emphasize that downregulation of respiratory chain enzyme complex subunits and inhibition of oxidative phosphorylation pathways play crucial roles in the pathophysiology of POI. In conclusion, our utilization of long-read sequencing has refined the annotation information within the POI transcriptional profile. This valuable data provides novel insights for further exploration into molecular regulatory networks and potential biomarkers associated with POI.
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Nanoporos , Insuficiencia Ovárica Primaria , Femenino , Humanos , Fosfatidilinositol 3-Quinasas/genética , Insuficiencia Ovárica Primaria/genética , Biomarcadores , Aprendizaje AutomáticoRESUMEN
Liquid crystal elastomers (LCE) and magnetic soft materials are promising active materials in many emerging fields, such as soft robotics. Despite the high demand for developing active materials that combine the advantages of LCE and magnetic actuation, the lack of independent programming of the LCE nematic order and magnetization in a single material still hinders the desired multi-responsiveness. In this study, a ferromagnetic LCE (magLCE) ink with nematic order and magnetization is developed that can be independently programmed to be anisotropic, referred to as "dual anisotropy", via a customized 3D-printing platform. The magLCE ink is fabricated by dispersing ferromagnetic microparticles in the LCE matrix, and a 3D-printing platform is created by integrating a magnet with 3-DoF motion into an extrusion-based 3D printer. In addition to magnetic fields, magLCEs can also be actuated by heating sources (either environmental heating or photo-heating of the embedded ferromagnetic microparticles) with a high energy density and tunable actuation temperature. A programmed magLCE strip robot is demonstrated with enhanced adaptability to complex environments (different terrains, magnetic fields, and temperatures) using a multi-actuation strategy. The magLCE also has potential applications in mechanical memory, as demonstrated by the multistable mechanical metastructure array with remote writability and stable memory.
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OBJECTIVE: Repeated pregnancy loss has been shown to be related to decidual immune imbalance. Metformin has been found to promote a shift in the Th17/Treg balance towards immune tolerance. Our research aims to evaluate and obtain further information on the role and potential mechanism of metformin on Th17/Treg balance in the early pregnancy decidua. METHODS: Decidual immune cells from normal pregnancy women were treated with metformin, pro-inflammatory cytokines or metformin + cytokines respectively. The mRNA expression levels of STAT3, STAT5, RORC and Foxp3 were detected by qRT-PCR. The proportions of Th17 and Treg cells, the stability of Treg cells, and the STATs phosphorylation levels of T cells were evaluated by flow cytometry. The cytokine concentrations in the culture medium were detected by ELISA. RESULTS: After treated with metformin, indicators related to immune tolerance, including the mRNA expression and phosphorylation levels of STAT5, mRNA expression level of Foxp3, the proportion of Treg cell, and the IL-10 concentration increased significantly. Indicators related to immune rejection including the mRNA expression level of STAT3, the proportion of Th17 cell, and the IL-17A concentration showed a significant decrease. In inflammatory conditions, the proportion of Th-like Treg cells increased. Metformin promoted CD25 expression to maintain Treg cell stability. CONCLUSION: Metformin has beneficial effects on immunological tolerance at the maternal-foetal interface in early pregnancy. The underlying mechanism may be that metformin restores the Th17/Treg balance by changing the expression of STATs, which is conducive to establishing maternal-foetal immune tolerance.
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PURPOSE: To explore the underlying mechanism of primordial follicle loss in the early period following ovarian tissue transplantation (OTT). METHODS: BNIP3 was selected through bioinformatic protocols, as the hub gene related to autophagy during OTT. BNIP3 and autophagy in mice ovarian grafts and in hypoxia-mimicking KGN cells were detected using immunohistochemistry, transmission electron microscopy (TEM), western blotting, qPCR, and fluorescence staining. The regulatory role played by BNIP3 overexpression and the silencing of KGN cells in autophagy via the mTOR/ULK1 pathway was investigated. RESULTS: Ultrastructure examination showed that autophagic vacuoles increased after mice ovarian auto-transplantation. The BNIP3 and autophagy-related proteins (Beclin-1, LC3B, and SQSTM1/p62) in mice ovarian granulosa cells of primordial follicle from ovarian grafts were altered compared with the control. Administration of an autophagy inhibitor in mice decreased the depletion of primordial follicles. In vitro experiments indicated that BNIP3 and autophagy activity were upregulated in KGN cells treated with cobalt chloride (CoCl2). The overexpression of BNIP3 activated autophagy, whereas the silencing of BNIP3 suppressed it and reversed the autophagy induced by CoCl2 in KGN cells. Western blotting analysis showed the inhibition of mTOR and activation of ULK1 in KGN cells treated with CoCl2 and in the overexpression of BNIP3, and the opposite results following BNIP3 silencing. The activation of mTOR reversed the autophagy induced by BNIP3 overexpression. CONCLUSIONS: BNIP3-induced autophagy is crucial in primordial follicle loss during OTT procedure, and BNIP3 is a potential therapeutic target for primordial follicle loss after OTT.
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Cobalto , Serina-Treonina Quinasas TOR , Femenino , Ratones , Animales , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/metabolismo , Cobalto/farmacología , Folículo Ovárico/metabolismo , Autofagia/genética , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Proteínas MitocondrialesRESUMEN
Thermosets such as silicone are ubiquitous. However, existing manufacturing of thermosets involves either a prolonged manufacturing cycle (e.g., reaction injection molding), low geometric complexity (e.g., casting), or limited processable materials (e.g., frontal polymerization). Here, we report an in situ dual heating (ISDH) strategy for the rapid 3D printing of thermosets with complex structures and diverse rheological properties by incorporating direct ink writing (DIW) technique and a heating-accelerated in situ gelation mechanism. Enabled by an integrated Joule heater at the printhead, extruded thermosetting inks can quickly cure in situ, allowing for DIW of various thermosets with viscosities spanning five orders of magnitude, printed height over 100 mm, and high resolution of 50 µm. We further demonstrate DIW of a set of heterogenous thermosets using multiple functional materials and present a hybrid printing of a multilayer soft electronic circuit. Our ISDH strategy paves the way for fast manufacturing of thermosets for various emerging fields.
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Background: The metabolic characteristics of premature ovarian insufficiency (POI), a reproductive endocrine disease characterized by abnormal sex hormone metabolism and follicle depletion, remain unclear. Metabolomics is a powerful tool for exploring disease phenotypes and biomarkers. This study aims to identify metabolic markers and construct diagnostic models, and elucidate the underlying pathological mechanisms for POI. Methods: Non-targeted metabolomics was utilized to characterize the plasma metabolic profile of 40 patients. The metabolic markers were identified through bioinformatics and machine learning, and constructed an optimal diagnostic model by classified multi-model analysis. Enzyme-linked immunosorbent assay (ELISA) was used to verify antioxidant indexes, mitochondrial enzyme complexes, and ATP levels. Finally, integrated transcriptomics and metabolomics were used to reveal the dysregulated pathways and molecular regulatory mechanisms of POI. Results: The study identified eight metabolic markers significantly correlated with ovarian reserve function. The XGBoost diagnostic model was developed based on six machine learning models, demonstrating its robust diagnostic performance and clinical applicability through the evaluation of receiver operating characteristic (ROC) curve, decision curve analysis (DCA), calibration curve, and precise recall (PR) curve. Multi-omics analysis showed that mitochondrial respiratory chain electron carrier (CoQ10) and enzyme complex subunits were down-regulated in POI. ELISA validation revealed an elevation in oxidative stress markers and a reduction in the activities of antioxidant enzymes, CoQ10, and mitochondrial enzyme complexes in POI. Conclusion: Our findings highlight that mitochondrial dysfunction and energy metabolism disorders are closely related to the pathogenesis of POI. The identification of metabolic markers and predictive models holds significant implications for the diagnosis, treatment, and monitoring of POI.
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Menopausia Prematura , Insuficiencia Ovárica Primaria , Femenino , Humanos , Antioxidantes , Insuficiencia Ovárica Primaria/diagnóstico , Insuficiencia Ovárica Primaria/genética , Insuficiencia Ovárica Primaria/patología , Biomarcadores , Perfilación de la Expresión GénicaRESUMEN
This study aimed to analyse the expression of Sirt1/FoxO1 pathway in the placenta of patients with preeclampsia (PE). Clinical data of 111 PE patients were retrospectively analysed and divided into mild group (n = 61) and severe group (n = 50) according to the severity of condition. Another 45 healthy mothers were selected as healthy group. The value of Sirt1/FoxO1 pathway-related proteins in predicting prognosis of PE patients was analysed. The severe group had higher Sirt1 and lower FoxO1 protein expressions than the mild and healthy groups (p < 0.05). Sirt1 protein expression was positively correlated with ROS, LHP, NOX4, IL-1ß, IL-6, HMGB1, CRP, VCAM-1, Caspase-3, Fas, Apaf-1 and ET-1 in PE patients (r > 0, p < 0.05), while FoxO1 protein expression was negatively correlated with these indices (r < 0, p < 0.05). Sirt1 protein expression was negatively correlated with SOD, CAT, GSH-Px, Bcl-2, Mcl-2, P57kip2 and NO (r < 0, p < 0.05), while FoxO1 protein expression was positively correlated with these indices (r > 0, p < 0.05). The expression of Sirt1/FoxO1 pathway related proteins was abnormal in placenta of PE patients, and was closely related to the expression of oxidative stress, inflammatory response, endothelial damage factors and apoptotic molecules.IMPACT STATEMENTWhat is already known on this subject? The Sirt1/FoxO1 pathway is abnormally expressed in the placenta of preeclampsia patients, with Sirt1 protein expression up-regulated and FoxO1 protein expression down-regulated, both of which are closely related to the expression of oxidative stress, inflammatory response, endothelial damage factors and apoptotic molecules in the placenta of preeclampsia patients.What do the results of this study add? The results of this study add to the knowledge about the role of the Sirt1/FoxO1 pathway in the pathogenesis of preeclampsia.What are the implications of these findings for clinical practice and/or further research? These findings provide a basis for predicting poor pregnancy outcomes in patients with preeclampsia in clinical practice.
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Preeclampsia , Sirtuina 1 , Embarazo , Humanos , Femenino , Proteína Forkhead Box O1/metabolismo , Sirtuina 1/metabolismo , Preeclampsia/patología , Estudios Retrospectivos , Placenta/patología , PronósticoRESUMEN
Phthalates have been shown to have adverse effects on neurodevelopment, which may be gender-specific. However, the association between prenatal mixed exposure to phthalates and children's neurodevelopment remains inconsistent. We measured 15 prenatal serum phthalate levels and evaluated children's neurodevelopmental indicators using Gesell Developmental Schedule (GDS) (n = 750). Generalized linear regression was fitted to examine the association. Among boys, mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP) had adverse effects on gross motor [odds ratio (OR): 7.38, 95% confidence interval (CI):1.42, 38.46]. For gross motor in boys, joint effect was discovered between mono-2-ethylhexyl phthalate (MEHP) and MEHHP. Moreover, synergistic effects were found for MEHP with vanadium and cadmium, and antagonistic effects for MEHP with magnesium, calcium, titanium, iron, copper, selenium, rubidium, and strontium. We did not find statistically significant relationships in girls. In the 1st trimester, adverse effects were identified between mono-2-ethyl-5-oxoyhexyl phthalate (MEOHP) and adaptation (P = 0.024), and monomethyl phthalate (MMP) with social area (P = 0.017). In the 2nd trimester, MEHHP had adverse effects on social area (P = 0.035). In summary, we found boys may be more vulnerable to the neurotoxicity than girls in gross motor, and we also discovered the detrimental effects of phthalates on children's neurodevelopment in the 1st and 2nd trimesters. Therefore, the supplementation of appropriate elements in the 1st and 2nd trimesters may help reduce the adverse effects of phthalates on children's neurodevelopment, especially among boys.
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Contaminantes Ambientales , Ácidos Ftálicos , Embarazo , Masculino , Niño , Femenino , Humanos , Estudios de Cohortes , Cohorte de Nacimiento , China , Ácidos Ftálicos/toxicidad , Exposición a Riesgos Ambientales/análisisRESUMEN
BACKGROUND: Impaired neurodevelopment of children has become a growing public concern; however, the associations between metals exposure and neurocognitive function have remained largely unknown. OBJECTIVES: We systematically evaluated the associations of multiple metals exposure during pregnancy and childhood on the neurodevelopment of children aged 2-3 years. METHODS: We measured 22 metals in the serum and urine among703 mother-child pairs from the Guangxi Birth Cohort Study. The neurocognitive development of children was assessed by the Gesell Development Diagnosis Scale (GDDS; Chinese version). Multiple linear regression models were used to evaluate the relationship between the metals (selected by elastic net regression) and the outcomes. The Bayesian kernel machine regression (BKMR) was used to evaluate the possible joint effect between the multiple metal mixture and the outcomes. RESULTS: Prenatal aluminum (Al) exposure was negatively associated with the fine motor developmental quotient (DQ) (ß = -1.545, 95%CI: 2.231, -0.859), adaption DQ (ß = -1.182, 95%CI: 1.632, -0.732), language DQ (ß = -1.284, 95% CI: 1.758, -0.809), and social DQ (ß = -1.729, 95% CI: 2.406, -1.052) in the multi-metal model. Prenatal cadmium (Cd) exposure was negatively associated with gross motor DQ (ß = -2.524, 95% CI: 4.060, -0.988), while postpartum Cd exposure was negatively associated with language DQ (ß = -1.678, 95% CI: 3.227, -0.129). In stratified analyses, infants of different sexes had different sensitivities to metal exposure, and neurobehavioral development was more significantly affected by metal exposure in the first and second trimester. BKMR analysis revealed a negative joint effect of the Al, Cd, and selenium (Se) on the language DQ score; postpartum Cd exposure played a major role in this relationship. CONCLUSION: Prenatal exposure to Al, Ba, Cd, molybdenum (Mo), lead (Pb), antimony (Sb), and strontium (Sr), and postpartum exposure to cobalt (Co), Cd, stannum (Sn), iron (Fe), nickel (Ni), and Se are associated with neurological development of infants. The first and second trimester might be the most sensitive period when metal exposure affects neurodevelopment.
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Metales , Teorema de Bayes , Preescolar , China , Estudios de Cohortes , Femenino , Humanos , Lactante , Metales/toxicidad , Embarazo , Estudios ProspectivosRESUMEN
OBJECTIVE: Repeated implantation failure (RIF) has been shown related to maternal immune imbalance. Many studies suggested that prednisone promoted the Th17/Treg balance shift to the direction of immune tolerance. Our study aimed to evaluate the role of prednisone in Th17/Treg balance and pregnancy outcome in RIF patients. STUDY DESIGN AND MAIN OUTCOME MEASURES: Peripheral blood of healthy fertile controls and RIF patients were collected at the late proliferation phase. The population of Treg and Th17 cells, the expression of Foxp3 and RORC mRNA and the concentration of IL-17A, IL-23 and IL-10 were detected by flow cytometry, qRT-PCR and enzyme-linked immunosorbent assay. RIF patients were given oral prednisone 10 mg daily from the late proliferation phase of the cycle before FET. After one month of treatment, the above immune indicators were tested, and natural cycle frozen embryo transfer was performed. RESULTS: The Treg cells proportion and IL-10 concentration in peripheral blood of RIF patients was lower than that of NF group, while the proportion of Th17 cells and concentration of proinflammatory cytokine were significantly higher. After prednisone treatment, the indicators related to immune tolerance increased significantly. Five out of 19 RIF patients were successful pregnancy after FET, in which, one had an early miscarriage and four live births. No pregnancy complications and fetal abnormalities were observed. CONCLUSIONS: We report the beneficial effect of prednisone on RIF patients. The underlying mechanism may attribute to shift the Treg/Th17 immune balance to a Treg bias, and enhance embryo implantation, ultimately improve pregnancy outcomes.
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Implantación del Embrión/efectos de los fármacos , Fertilización In Vitro/métodos , Infertilidad Femenina/terapia , Prednisona/administración & dosificación , Linfocitos T Reguladores/efectos de los fármacos , Administración Oral , Adulto , Estudios de Casos y Controles , Implantación del Embrión/inmunología , Transferencia de Embrión/estadística & datos numéricos , Femenino , Fertilización In Vitro/estadística & datos numéricos , Voluntarios Sanos , Humanos , Tolerancia Inmunológica/efectos de los fármacos , Infertilidad Femenina/sangre , Infertilidad Femenina/inmunología , Interleucina-10/sangre , Interleucina-10/metabolismo , Nacimiento Vivo , Embarazo , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/metabolismo , Células Th17/efectos de los fármacos , Células Th17/inmunología , Células Th17/metabolismo , Resultado del TratamientoRESUMEN
BACKGROUND: Human are widely exposed to multiple metals, some of which have suspected reproductive toxicity, but no human studies have investigated the developmental effects of prenatal metal exposure. OBJECTIVES: We aimed to evaluate the associations between prenatal multiple metal exposure and reproductive development in boys at 2-3 years using multi-pollutant approach. METHODS: This prospective study used data of 564 mother-child pairs recruited from the Guangxi Birth Cohort Study. Twenty serum metal concentrations were measured. Least absolute shrinkage and selection operator (LASSO) penalized regression was used to identify independent associations between prenatal multiple metal exposure and testicular volume (TV), and anogenital distance (AGD). Adjusted estimates were then obtained using multiple linear regression analysis, and the regression tree method was used to explore the interactions. RESULTS: Boys in the highest quartile of prenatal lead exposure had a 0.064 mL (95% CI: -0.124, -0.004) smaller ln-transformed TV, 0.060 cm (95% CI: -0.110, -0.011) shorter ln-transformed anopenile distance (AGDap), and 0.115 cm (95% CI: -0.190, -0.039) shorter ln-transformed anoscrotal distance (AGDas) than boys in the lowest quartile (all Ptrend < 0.05). Chromium was inversely with ln-transformed AGDap (ß = -0.078, 95% CI: -0.127, -0.030) and ln-transformed AGDas (ß = -0.113, 95% CI: -0.188, -0.038), while stibium was positivity associated with ln-transformed AGDap (ß = 0.091, 95% CI: 0.046, 0.136) and strontium was positivity associated with ln-transformed AGDas (ß = 0.120, 95% CI: 0.051, 0.189) (all Ptrend < 0.05). And the critical window of vulnerability may be the late pregnancy (the second and third trimester). Moreover, we detected interaction effects between lead, chromium and stibium on AGDap; lead, chromium and strontium on AGDas. CONCLUSIONS: The results suggest that prenatal exposure to lead, chromium, stibium and strontium may affect TV and/or AGD in infant boys. Potential mechanisms for the complex metal interactive effects during vulnerable periods are worthy of further investigation.
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Efectos Tardíos de la Exposición Prenatal , Canal Anal , Niño , China , Estudios de Cohortes , Femenino , Humanos , Lactante , Estudios Longitudinales , Masculino , Exposición Materna/efectos adversos , Embarazo , Estudios ProspectivosRESUMEN
In order to explore the predictive model for analyzing clinical pregnancy outcomes based on IVF-ET (in vitro fertilization and embryo transfer) and ICSI (Intracytoplasmic sperm injection) assisted reproductive technology (ART). METHODS: this study selected the embryo transfer (fresh) patients who received IVF-ET or ICSI treatment in the First Affiliated Hospital of Guangxi Medical University as the subjects. Moreover, the controlled ovarian stimulation (COS) and follow-up were conducted to collect relevant data for analysis, and finally a prediction model was established. RESULTS: The results showed that the patients were divided into different ovarian response groups at first. The age, bFSH and bFSH/bLH were the highest in the poor ovarian response group (POR), followed by the normal ovarian response group (NOR) and the lowest in the high ovarian response group (HOR). The area under the ROC curve was 0.669 according to the predictive model of pregnancy-related factors. The confidence interval of 94% was 0.629-0.697, with statistical significance (P = 0.000, P < 0.01). CONCLUSION: it can be concluded that in clinical pregnancy, for many related factors, regression equation can be used to establish a prediction model to diagnose the success rate of pregnancy. In conclusion, a prediction model can be built based on the relevant experimental results, to provide experimental reference ideas for increasing the success rate of ART in late clinical pregnancy, which is of great research significance.
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BACKGROUND: Long non-coding RNA (LncRNA) SNHG7 is involved in the development of multiple cancers. However, its role in cervical cancer (CC) has not been elucidated. This study aimed to explore the function of SNHG7 in CC progression and the underlying mechanisms. MATERIALS AND METHODS: The expression levels of SNHG7 and miR-485-5p in CC tissues and cell lines were measured by qPCR. Functional experiments including CCK-8 assay, wound healing assay, transwell assay, flow cytometry, Western blot, luciferases reporter assay and immunoprecipitation (RIP) were performed to explore the SNHG7/miR-485-5p/JUND pathway. Additionally, in vivo study was carried out by establishing tumor xenograft models. RESULTS: We found that SNHG7 was markedly enhanced in CC tissues and cell lines, and associated with poor clinical characteristics. In vitro, knockdown of SNHG7 inhibited CC cell proliferation, migration and invasion, as well as aggravated cell apoptosis. As to mechanism investigation, rescue experiments revealed that miR-485-5p inhibitor could partially reverse the effects on CC cells induced by SNHG7 knockdown. SNHG7 upregulated JUND expression via miR-485-5p. Moreover, tumor xenograft models were established to confirm the findings in vivo. CONCLUSION: SNHG7 promoted CC progression through miR-485-5p/JUND axis. The SNHG7/miR-485-5p/JUND pathway might provide a novel therapeutic target for CC treatment.
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This study aimed to investigate the effects of signal transducer and activators of transcription 3 (STAT3) phosphorylation on the function of decidual regulatory T (Treg) cells in unexplained recurrent spontaneous abortion (URSA) patients and to explore the mechanism of STAT3 in URSA. Treg cells were sorted out from the decidual tissue by magnetic beads. The inhibitor Stattic was utilized to alter the phosphorylation status of STAT3 (pSTAT3) in Treg cells. The proliferation and suppression of Treg cell were detected by flow cytometry, real-time quantitative fluorescent PCR and ELISA. The factors that caused the hyperphosphorylation of Treg cells were detected. Our results showed that the proportion of pSTAT3 cells in the decidual Treg cells of URSA patients was significantly increased. pSTAT3 inhibited the proliferation of Treg cells by downregulating the expression of STAT5 and Foxp3 and increased the number of responder T cells. pSTAT3 decreased the secretion of TGF-ß1 and IL-10 in Treg cells. Overexpression of pro-inflammatory cytokines IL-6 and IL-23 stimulated STAT3 phosphorylation in Treg cells. This study suggests that hyperphosphorylation of STAT3 impairs the proliferation, suppression and cytokine secretion of Treg cells, while inhibiting the phosphorylation of STAT3 restores these functions. These findings clarify the role of STAT3 in the pathogenesis of URSA and provide new ideas for the treatment of URSA.
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BACKGROUND: Currently, there are many studies researched the associations between maternal serum inflammatory indicators (i.e. ferritin, C-reactive protein [CRP], C3 and C4) and preterm birth (PTB). The results, however, are inconsistent. Therefore, the aim of this study was to estimate the relationship between maternal serum inflammatory indicators and PTB in a nested case-control (NCC)study. METHODS: A NCC study was conducted by Guangxi Birth Cohort Study which enrolled a total of 6203 pregnant women between 50/7 and 346/7 weeks of gestational age (wGA) from six cities in China between 2015 and 2016. There were 206women who delivered preterm (< 370/7 wGA), and 412 women who delivered term birth, those women were matched by maternal age, birth place, gender of infants, and wGA at blood collection. The inflammatory indicators were quantified by immunoturbidimetric methods. RESULTS: Highest quartile concentrations of all inflammatory indicators were determined versus median. After adjusting for maternal age, high levels of CRP (CRP > 16.60 mg/L) are related to the risk of PTB (OR = 2.16, 95% CI: 1.02-4.56, p = 0.044) in the first trimester. The association of C3 was extremely related to those who delivered PTB (OR = 2.53, 95% CI: 1.14-5.64, p = 0.023) in the first trimester. Moreover, no significant associations were found in C4 (p = 0.079) and ferritin (p = 0.067) between PTB. CONCLUSIONS: Elevated concentrations of CRP and C3 in the first trimester were associated with increased risk of PTB. Inflammatory indicators may act a pivotal part in early diagnosis and prognosis of PTB.