Exosome-delivered miR-410-3p reverses epithelial-mesenchymal transition, migration and invasion of trophoblasts in spontaneous abortion.

Current studies have indicated that insufficient trophoblast epithelial-mesenchymal transition (EMT), migration and invasion are crucial for spontaneous abortion (SA) occurrence and development. Exosomal miRNAs play significant roles in embryonic development and cellular communication. Hereon, we explored the roles of serum exosomes derived from SA patients on trophoblast EMT, migration and invasion. Exosomes were isolated from normal control (NC) patients with abortion for unplanned pregnancy and SA patients, then characterized by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA) and western blotting. Exosomal miRNA profiles were identified by miRNA sequencing. The effects of serum exosomes on trophoblast migration and invasion were detected by scratch wound healing and transwell assays, and other potential mechanisms were revealed by quantitative real-time PCR (RT-PCR), western blotting and dual-luciferase reporter assay. Finally, animal experiments were used to explore the effects of exosomal miR-410-3p on embryo absorption in mice. The serum exosomes from SA patients inhibited trophoblast EMT and reduced their migration and invasion ability in vitro. The miRNA sequencing showed that miR-410-3p was upregulated in SA serum exosomes. The functional experiments showed that SA serum exosomes restrained trophoblast EMT, migration and invasion by releasing miR-410-3p. Mechanistically, SA serum exosomal miR-410-3p inhibited trophoblast cell EMT, migration and invasion by targeting TNF receptor-associated factor 6 (TRAF6) at the post-transcriptional level. Besides, SA serum exosomal miR-410-3p inhibited the p38 MAPK signalling pathway by targeting TRAF6 in trophoblasts. Moreover, milk exosomes loaded with miR-410-3p mimic reached the maternal-fetal interface and aggravated embryo absorption in female mice. Clinically, miR-410-3p and TRAF6 expression were abnormal and negatively correlated in the placental villi of SA patients. Our findings indicated that exosome-derived miR-410-3p plays an important role between SA serum and trophoblasts in intercellular communication, suggesting a novel mechanism by which serum exosomal miRNA regulates trophoblasts in SA patients.

[Systematic evaluation and sequential Meta-analysis of modified Xuefu Zhuyu Decoction combined with Western medicine in treatment of leiomyoma].

CNKI, PubMed and other databases were retrieved to extract eligible randomized controlled trial(RCT) about modified Xuefu Zhuyu Decoction(MXZD) combined with Western medicine(trial group) versus Western medicine alone(control group) in the treatment of leiomyoma. Therefore, a total of 25 RCTs were included, involving 2 328 patients. Bias risk evaluation tool in Cochrane Handbook 5.1.0 was used for evaluating the quality of these RCTs. Meta-analysis was performed for the reported indicators, including total efficiency, serum hormone level [progesterone(P), luteinizing hormone(LH), estradiol(E_2), follicle stimulating hormone(FSH)], uterine size, fibroids size and adverse reactions by using Stata 14.0 software. Meta-analysis showed that the total efficiency(RR=1.21,95%CI[1.17,1.25],P<0.05) of trial group was better than that of control group. Serum hormone level(WMD_P=-3.86,95%CI[-4.31,-3.41],P<0.05; WMD_(LH)=-3.64,95%CI[-4.47,-2.82],P<0.05; WMD_(E_2)=-39.99,95%CI[-53.45,-26.52],P<0.05; WMD_(FSH)=-3.79,95%CI[-4.86,-2.72],P<0.05), uterine size(WMD=-50.02,95%CI[-55.98,-44.06],P<0.05), fibroids size(WMD=-15.79,95%CI[-18.11,-13.46],P<0.05) and adverse reactions(RR=0.65,95%CI[0.48,0.88],P<0.05) of trial group were all lower than those of control group, with statistical significances. Trial sequential analysis(TSA) was performed by using TSA 0.9 software, and showed a reliable therapeutic effect of the experimental group. In short, our study indicated that modified Xuefu Zhuyu Decoction combined with Western medicine had a better therapeutic effect on leiomyoma than Western medicine alone, but more high-quality studies are needed to verify this conclusion in the future.

Association of Thiamine Intake with Human Papillomavirus (HPV) Infection in American Women: A Secondary Data Analysis Based on the National Health and Nutrition Examination Survey from 2003 to 2016.

BACKGROUND Studies have shown that thiamine intake is associated with cervical cancer, but the relationship between thiamine and HPV infection remains unclear. In the present study, we used the National Health and Nutrition Examination Survey (NHANES) database to investigate whether HPV infection was associated with thiamine intake. MATERIAL AND METHODS A total of 13 471 women ages 18-59 years were selected from the NHANES database from 2003 to 2016. Using thiamine intake as the independent variable, HPV infection as the dependent variable, and sociodemographic data and other data as the covariates, we analyzed the relationship between thiamine and HPV infection by conducting a weighted logistic regression model in a cross-sectional research design. RESULTS The two-piecewise linear model indicated the inflection point of thiamine intake was 2.07 mg. On the left side of the inflection point, the difference in the thiamine intake of log2 conversion was related to the difference of 0.82 in HPV infection, which means that the increase of every 1 unit increase in thiamine intake is associated with the decrease of the HPV infection by 18%. On the right side of the inflection point, we did not observe a correlation between HPV infection and thiamine intake. CONCLUSIONS Thiamine intake is negatively correlated with HPV infection. Intake of an appropriate amount of thiamine can prevent HPV infection. The best preventive effect can be achieved when the intake is about 2 mg, and excessive intake will not increase the preventive effect.

Colla corii asini might upregulate ZNF471 and THOC5 by KRAB domain-containing zinc-finger protein pathway and THO complex subunit 5 pathway to improve anemia of pregnant women with ß-thalassemia.

Pregnant patients with ß-thalassemia are more likely to have progressive anemia which expose them to risk of adverse pregnancy outcomes, blood transfusion, and iron overload. Results from our previous study indicated that Colla corii asini (CCA, E'jiao), a natural ingredient of traditional Chinese medicine, could significantly increase hemoglobin level of pregnant women with ß- thalassemia, but the underlying molecular mechanism was unclear. Thus, we applied high-throughput transcriptome sequencing to study the transcriptomic change before and after the CCA treatment. Twenty eligible pregnant women were recruited and randomized to either the CCA treatment group or the blank control group in a 3:1 ratio. Patients in the treatment group orally received daily 15 g CCA powder for 4 weeks. We analyzed the therapeutic effect indexes and the transcriptomic change in subjects' peripheral blood before and after treatment. We found that ß CD 41-42(-TTCT)/ßA was the main genotype of the subjects. The regulatory impact of CCA treatment became more evident among the subjects of genotype ß CD 41-42(-TTCT)/ßA. Gene ontogenesis analysis revealed that the top five molecular functions of differentially expressed genes were involved in membrane functionality and cellular structure. We further identified two consistent upregulated genes ZNF471 and THOC5 in the effective treatment group, which were engaged in Kruppel-associated box (KRAB) domain-containing zinc-finger protein pathway and THOC5 pathway, respectively. Based on our current findings, we hypothesize that the anti-anemia effect of CCA on pregnant women with ß-thalassemia might be related to translation regulation of spectrin synthesis, membrane stability, and eventually prolonged the life span of erythrocytes.

Hybrid PbS Quantum-Dot-in-Perovskite for High-Efficiency Perovskite Solar Cell.

In this study, a facile and effective approach to synthesize high-quality perovskite-quantum dots (QDs) hybrid film is demonstrated, which dramatically improves the photovoltaic performance of a perovskite solar cell (PSC). Adding PbS QDs into CH3 NH3 PbI3 (MAPbI3 ) precursor to form a QD-in-perovskite structure is found to be beneficial for the crystallization of perovskite, revealed by enlarged grain size, reduced fragmentized grains, enhanced characteristic peak intensity, and large percentage of (220) plane in X-ray diffraction patterns. The hybrid film also shows higher carrier mobility, as evidenced by Hall Effect measurement. By taking all these advantages, the PSC based on MAPbI3 -PbS hybrid film leads to an improvement in power conversion efficiency by 14% compared to that based on pure perovskite, primarily ascribed to higher current density and fill factor (FF). Ultimately, an efficiency reaching up to 18.6% and a FF of over ≈0.77 are achieved based on the PSC with hybrid film. Such a simple hybridizing technique opens up a promising method to improve the performance of PSCs, and has strong potential to be applied to prepare other hybrid composite materials.

[Advantages and evidences research on Chinese medicine for treatment of pelvic inflammatory disease].

Pelvic inflammatory disease is an infectious disease. At present, Western medicine is mainly treated with antibiotics. However, the situation of antibiotics abuse is so grim that the potential risks such as the imbalance of bacteria, the resistance of bacteria, the production of super bacteria and the increase of adverse reactions are becoming more and more serious. Therefore, it is urgent to find a way to supplement or substitute antibiotics for the treatment of this disease. Traditional Chinese medicine treatment of the disease is effective and has its unique advantages. This paper mainly discusses the advantages and evidences of traditional Chinese medicine (TCM) treatment of pelvic inflammatory disease, to further prove the effectiveness and safety of TCM treatment and to provide medical evidence of reducing antibiotics use.

Successful term delivery of spontaneous twin pregnancy in a woman with bicorporeal septate uterus: A case report.

Herein, we report the first case of successful term delivery of twins in a patient with bicorporeal septate uterus via natural conception. The patient had been diagnosed with complete septate, didelphys and bicornuate uterus during different phases of her three pregnancies. Based on follow-up data at six weeks and then six months post-partum of the last pregnancy, we found that the abnormalities presented in our case did not fit the criteria of any categories following American Fertility Society and European Society of Human Reproduction and Embryology-European Society for Gynaecological Endoscopy classification systems. After comprehensive review of the uterine morphologic characteristics, embryology and pregnancy outcome, we considered 'bicorporeal septate uterus' the most appropriate diagnosis. This case emphasized the atypical changes of uterine shape as twin pregnancy advances and its influence on productive performance and pregnancy outcome in uterine malformation. It also raised concern regarding the usability and comprehensiveness of the two most popular classification systems.

Successful Treatment of a Recurrent Cesarean Scar Pregnancy by Transvaginal Cesarean Scar Pregnancy Lesion Resection: A Case Report.

Background: Cesarean scar pregnancy (CSP) is a type of ectopic pregnancy with the gestation sac located on a previous cesarean scar. Recurrent CSP (RCSP) is the occurrence of 2 or more consecutive CSPs. Until this case, there have been only 8 previous reported cases of RCSPs in the English-language literature. Case: A 30-year-old, Chinese woman was admitted to our hospital for RCSP. We had successfully terminated her first CSP by a series of treatments including uterine arterial embolization with local methotrexate injection, mifepristone, and misoprostol administration, as well as an ultrasound-guided suction curettage evacuation. However, this time we performed only a transvaginal CSP lesion resection, which achieved an improved outcome. Conclusion: This case highlights the likelihood of RCSP and the need for transvaginal CSP lesion resection to decrease the risk of RCSP in CSP patients who desire future pregnancy.

Network Pharmacology, Molecular Docking, and Experimental Validation on Guiluoshi Anzang Decoction Against Premature Ovarian Insufficiency.

BACKGROUND AND OBJECTIVES: Premature Ovarian Insufficiency (POI) is a disease suffered by women under the age of 40 when ovarian function has declined, seriously affecting both the physical and mental health of women. Guiluoshi Anzang decoction (GLSAZD) has been used for a long time and has a unique therapeutic effect on improving ovarian function. This study aims to investigate the mechanism of GLSAZD in treating POI through network pharmacology, molecular docking, and experimental verification. METHODS: In this study, the active ingredients of Guiluoshi Anzang Decoction and the targets of POI were obtained from TCMSP, BATMANN-TCM, Uniprot, GeneCards, and other databases, and network pharmacology analysis was performed. Molecular docking was conducted to validate the affinity of the main active ingredient of GLSAZD to key POI targets. A POI SD rat model was established, and HE staining, ELISA, Real-time PCR, and Western blot experiments were performed to verify the predicted core targets and the therapeutic effects. RESULTS: 10 core targets and the top 5 ingredients were screened out. Molecular docking showed core targets AKT1, CASP3, TNF, TP53, and IL6 had stable binding with the core 5 ingredients quercetin, kaempferol, beta-sitosterol, luteolin, and Stigmasterol. GO and KEGG enrichment analysis demonstrated the mechanism involved in the positive regulation of gene expression, PI3K-AKT signaling pathway, and apoptosis signaling pathways. Animal experiments indicated GLSAZD could up-regulate the protein expression of p-PI3K and p-AKT1 and the mRNA expression of STAT3 and VEGF, down-regulate TP53 and Cleaved Caspase-3 protein expression in rat`s ovarian tissues and serum TNF-α and IL-6 protein levels, activate PI3K-AKT signaling pathway and inhibit the apoptosis signaling pathway. CONCLUSION: GLSAZD treats POI through multi-component, multi-target, and multi-pathway approaches. This study provided evidence for its clinical application in treating POI and shed light on the study of traditional medicine of the Guangxi Zhuang Autonomous Region in China.

Danggui Shaoyao San protects cyclophosphamide-induced premature ovarian failure by inhibiting apoptosis and oxidative stress through the regulation of the SIRT1/p53 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: It has been reported that apoptosis and oxidative stress are related to cyclophosphamide (CYC)-induced premature ovarian failure (POF). Therefore, anti-apoptotic and anti-oxidative stress treatments exhibit therapeutic efficacy in CYC-induced POF. Danggui Shaoyao San (DSS), which has been extensively used to treat gynecologic diseases, is found to inhibit apoptosis and reduce oxidative stress. However, the roles of DSS in regulating apoptosis and oxidative stress during CYC-induced POF, and its associated mechanisms are still unknown. AIM OF THE STUDY: This work aimed to investigate the roles and mechanisms of DSS in inhibiting apoptosis and oxidative stress in CYC-induced POF. MATERIALS AND METHODS: CYC (75 mg/kg) was intraperitoneally injected in mice to construct the POF mouse model for in vivo study. Thereafter, alterations of body weight, ovary morphology and estrous cycle were monitored to assess the ovarian protective properties of DSS. Serum LH and E2 levels were analyzed by enzyme-linked immunosorbent assay (ELISA). Hematoxylin-eosin (HE) staining was employed for examining ovarian pathological morphology and quantifying follicles in various stages. Meanwhile, TUNEL staining and apoptosis-related proteins were adopted for evaluating apoptosis. Oxidative stress was measured by the levels of ROS, MDA, and 4-HNE. Western blot (WB) assay was performed to detect proteins related to the SIRT1/p53 pathway. KGN cells were used for in vitro experiment. TBHP stimulation was carried out for establishing the oxidative stress-induced apoptosis cell model. Furthermore, MTT assay was employed for evaluating the protection of DSS from TBHP-induced oxidative stress. The anti-apoptotic ability of DSS was evaluated by hoechst/PI staining, JC-1 staining, and apoptosis-related proteins. Additionally, the anti-oxidative stress ability of DSS was measured by detecting the levels of ROS, MDA, and 4-HNE. Proteins related to SIRT1/p53 signaling pathway were also measured using WB and immunofluorescence (IF) staining. Besides, SIRT1 expression was suppressed by EX527 to further investigate the role of SIRT1 in the effects of DSS against apoptosis and oxidative stress. RESULTS: In the in vivo experiment, DSS dose-dependently exerted its anti-apoptotic, anti-oxidative stress, and ovarian protective effects. In addition, apoptosis, apoptosis-related protein and oxidative stress levels were inhibited by DSS treatment. DSS treatment up-regulated SIRT1 and down-regulated p53 expression. From in vitro experiment, it was found that DSS treatment protected KGN cells from TBHP-induced oxidative stress injury. Besides, DSS administration suppressed the apoptosis ratio, apoptosis-related protein levels, mitochondrial membrane potential damage, and oxidative stress. SIRT1 suppression by EX527 abolished the anti-apoptotic, anti-oxidative stress, and ovarian protective effects, as discovered from in vivo and in vitro experiments. CONCLUSIONS: DSS exerts the anti-apoptotic, anti-oxidative stress, and ovarian protective effects in POF mice, and suppresses the apoptosis and oxidative stress of KGN cells through activating SIRT1 and suppressing p53 pathway.

Gut microbiota and risk of polycystic ovary syndrome: Insights from Mendelian randomization.

Background: Polycystic ovary syndrome (PCOS) is a multifaceted endocrine and metabolic syndrome with complex origins and pathogenesis that has not yet been fully elucidated. Recently, the interconnection between gut microbiota and metabolic diseases has gained prominence in research, generating new insights into the correlation between PCOS and gut microbiota composition. However, the causal link between PCOS and gut microbiota remains relatively unexplored, indicating a crucial gap in current research. Methods: We conducted a two-sample Mendelian randomization analysis using summary statistics obtained from the MiBioGen Consortium's extensive genome-wide association studies (GWAS) meta-analysis, focusing on the gut microbiota. Summary statistics for PCOS were acquired from the FinnGen Consortium R7 release data. Various statistical approaches, including inverse variance weighted, MR-Egger, maximum likelihood, weighted model, and weighted median, have been employed to investigate the causal association between the gut microbiota and PCOS. Additionally, we performed a reverse causal analysis. Cochran's Q statistic was used to assess the heterogeneity of the instrumental variables. Regarding the relationships between PCOS and specific genera within the gut microbiota, a significance level of P < 0.05 was observed, but only when q ≥ 0.1. Results: Our analysis revealed that specific microbial genera, namely Bilophila (P = 4.62 × 10-3), Blautia (P = 0.02), and Holdemania (P = 0.04), displayed a protective effect against PCOS. Conversely, the presence of the Lachnospiraceae family of bacteria was associated with a detrimental effect on PCOS (P = 0.04). Furthermore, reverse Mendelian randomization analysis confirmed the significant influence of Lachnospiraceae on PCOS. No significant variations in instrumental variables or evidence of horizontal pleiotropy were observed. Conclusions: The results revealed a definitive causal link between PCOS and the presence of Bilophila, Blautia, Holdemania, and Lachnospiraceae in the gut microbiota. This discovery could provide pivotal insights, leading to novel preventive and therapeutic approaches for PCOS.

Identification of Key Molecules in Recurrent Miscarriage Based on Bioinformatics Analysis.

BACKGROUND: Recurrent Miscarriage (RM) affects 1% to 5% of couples, and the mechanisms still stay unclear. In this study, we explored the underlying molecular mechanism and potential molecular biomarkers of RM as well as constructed a miRNA-mRNA regulation network. METHODS: The microarray datasets GSE73025 and GSE22490, which represent mRNA and miRNA profiles, respectively, were downloaded from the Gene Expression Omnibus (GEO) database. Differentially Expressed Genes (DEGs) with p-value < 0.05 and fold-change > 2 were identified while the miRNAs with p-value < 0.05 and fold-change > 1.3 were considered as significant differentially expressed miRNAs (DEMs). RESULTS: A total of 373 DEGs, including 218 up-regulated genes and 155 down-regulated genes, were identified, while 138 up-regulated and 68 down-regulated DEMs were screened out. After functional enrichment analysis, we found GO Biological Process (BP) terms significantly enriched in the Fc-gamma receptor signaling pathway involved in phagocytosis. Moreover, signaling pathway analyses indicated that the neurotrophin signaling pathway (hsa04722) was the top KEGG enrichment. 6 hub genes (FPR1, C5AR1, CCR1, ADCY7, CXCR2, NPY) were screened out to construct a complex regulation network in RM because they had the highest degree of affecting the network. Besides, we constructed miRNA-mRNA network between DEMs target genes and DEGs in RM, including hsa-miR-1297- KLHL24 and hsa-miR-548a-5p-KLHL24 pairs. CONCLUSION: In conclusion, the novel differentially expressed molecules in the present study could provide a new sight to explore the pathogenesis of RM as well as potential biomarkers and therapeutic targets for RM diagnosis and treatment.

The association between dietary fiber and infertility among US Women: The National Health and Nutrition Examination Survey, 2013-2018.

Introduction: Background: studies have shown that dietary factors are linked to female infertility, but the relation between dietary fiber consumption and infertility has not been proven. The purpose of this research was to investigate whether there is an independent association between dietary fiber intake and infertility in American women. Material and methods: a secondary analysis of the National Health and Nutrition Examination Survey (NHANES) dataset has been conducted, covering three cycles from 2013 to 2018. A total of 3,497 participants were included in the data analysis. The independent and dependent variables of interest were dietary fiber intake and infertility. Covariates included sociodemographic, questionnaire, diet, and physical examination data. Multiple logistic regression and sensitivity analyses were performed to investigate the relationship of dietary fiber intake with infertility. Results: each additional increase in log10 dietary fiber consumption was associated with a 32 % lower risk of infertility (OR, 0.68; 95 % CI, 0.48-0.96). The outcome is still robust in the minimally as well as the fully adjusted model. The possibility of a nonlinear association between dietary fiber intake and infertility was ruled out by the GAM model and smooth curve fitting. The results showed that there is an inverse linear correlation between dietary fiber intake and infertility. Conclusions: the association between intake of dietary fiber and infertility is linear, and increasing dietary fiber intake may be beneficial for lower infertility.

Introducción: Antecedentes: el consumo de fibra dietética es un factor importante en la infertilidad femenina. El objetivo del estudio fue investigar si existe una relación independiente entre el consumo de fibra dietética y la infertilidad en las mujeres estadounidenses. Material y métodos: se realizó un análisis secundario del conjunto de datos de la encuesta nacional de salud y nutrición (NHANES), que abarcó tres ciclos entre 2013 y 2018. Se incluyeron 3497 participantes para el análisis de datos. Las variables independientes y dependientes asociadas fueron la ingesta de fibra dietética y la infertilidad. Las covariables incluyeron datos sociodemográficos, de los cuestionarios, dietéticos y médicos. Se realizó un análisis de regresión logística multivariada y un análisis de sensibilidad para determinar la relación entre el consumo de fibra dietética y la infertilidad. Resultados: cada aumento log10 en el consumo de fibra dietética se asoció con una reducción del 32 % en el riesgo de infertilidad (OR: 0,68; intervalo de confianza del 95 %: 0,48-0,96). En el modelo mínimo y totalmente ajustado, los resultados siguen siendo robustos. El modelo GAM y el ajuste de curvas suavizadas descartaron la posibilidad de una relación no lineal entre la ingesta de fibra dietética y la infertilidad. Los resultados muestran una correlación lineal negativa entre la ingesta de fibra dietética y la infertilidad. Conclusiones: se observó una relación lineal entre la ingesta de fibra dietética y la infertilidad. El aumento de la ingesta de fibra dietética redujo la incidencia de la infertilidad.

Microbiome Characteristics in Early Threatened Miscarriage Study (MCETMS): a study protocol for a prospective cohort investigation in China.

INTRODUCTION: Studies have suggested that the vaginal microbiome and gut microbiome are involved in pregnancy-related diseases, but little exploration of the link with early miscarriage or threatened miscarriage (TM) has been done. Whether the characteristics of the vaginal microbiome and gut microbiome in early pregnancy are related to TM and early pregnancy outcomes remains unclear. METHODS AND ANALYSIS: The Microbiome Characteristics in Early Threatened Miscarriage Study (MCETMS) is a prospective investigation that will recruit 326 pregnant women with early TM. Pregnant women will be enrolled at 4-8 weeks of gestation, and their vaginal secretions, faecal samples, clinical data and sociodemographic characteristics will be collected prospectively. Pregnant women with TM will be followed up to 12 weeks of gestation to determine the early pregnancy outcomes (ongoing pregnancy or pregnancy loss). DNA will be extracted from the collected samples and will be analysed by 16S rRNA gene sequencing. ETHICS AND DISSEMINATION: The MCETMS study protocol has been approved by the Ethics Committee of the First Affiliated Hospital of Guangzhou Traditional Chinese Medical University (ZYYECK[2020]051). Dissemination of study findings will occur through peer-reviewed journals, conferences and presentations. TRIAL REGISTRATION NUMBER: ChiCTR2000041172.

Vaginal Atopobium is Associated with Spontaneous Abortion in the First Trimester: a Prospective Cohort Study in China.

Spontaneous abortion (SA) has received more and more attention in light of its increasing incidence. However, the causes and pathogenesis of SA remain largely unknown, especially for those without any pathological features. In this study, we characterized the vaginal microbiota diversity and composition of pregnant women in their first trimester and evaluated the association between the vaginal microbiota and SA before 12 weeks of gestation. Participants' bacterial profiles were analyzed by 16S rRNA gene sequencing in the V3-V4 regions at 5-8 weeks of gestation. A total of 48 patients with SA at 12 weeks of gestation were included as the study group, while 116 women with normal pregnancies (NPs) were included as a control group. The results indicated that the richness of the vaginal microbiome in SA patients was higher (Chao1, P < 0.05) and different in composition relative to that of women with NPs (unweighted UniFrac, R = 0.15, P < 0.01; binary Jaccard, R = 0.15, P < 0.01). Furthermore, the genus Apotobium was significantly enriched in SA patients. An extreme gradient-boosting (XGBoost) analysis was able to classify Atopobium-induced SA more reliably (area under the receiver operating characteristic curve, 0.69; threshold, 0.01%). Moreover, after adjusting for potential confounders, the results showed a robust association between Apotobium and SA (as a categorical variable [<0.01%]; adjusted odds ratio, 2.9; 95% confidence interval, 1.3 to 6.5; P = 0.01). In conclusion, higher vaginal Apotobium levels were associated with SA in the first trimester. IMPORTANCE Spontaneous abortion (SA) is the most common adverse pregnancy outcome in the first trimester. The causal drivers of SA have become a substantial challenge to reveal and overcome. We hypothesize that vaginal microbial dysbiosis is associated with SA, as it was related to several female reproductive disorders in previous studies. In our study, we characterized the vaginal microbiota of patients with SA at 12 weeks of gestation as the study group, and women with normal pregnancies were enrolled as a control group. Generally, significant differences were discovered in the vaginal microbiota between the two groups. Our study also revealed that Apotobium may play an important role in the pathogenesis of SA. To our knowledge, this study is the first detailed elaboration of the vaginal microbiota composition and vaginal Apotobium in association with SA. We believe that our findings will inspire more researchers to consider dynamic changes in the vaginal microbiota as critical features for further studies of nosogenesis not only for SA but also other reproductive diseases.

Zuogui pills maintain the stemness of oogonial stem cells and alleviate cyclophosphamide-induced ovarian aging through Notch signaling pathway.

BACKGROUND: Zuogui pills (ZGP), a classical prescription of traditional Chinese medicine, have been widely used in the treatment of ovarian aging. Previous studies have demonstrated its efficacy on protecting ovarian aging, and the mechanisms were mostly relevant to inhibiting the apoptosis of follicles and activating the primordial follicles. However, whether ZGP could stimulate the oogonial stem cells (OSCs) to refresh the follicle pool remains poorly understood. PURPOSE: To investigate the effects of ZGP on the stemness of OSCs in cyclophosphamide (Cy)-induced ovarian aging. STUDY DESIGN AND METHODS: Female Sprague-Dawley (SD) rats were randomly divided into 8 groups: control group, model group, ZGP groups (low / high dose groups), estradiol valerate (EV) groups (low / high dose groups), DAPT group and DAPT+ZGP-L group. After modeling with Cy, the ZGP groups and EV groups were treated with ZGP and EV for 8 weeks respectively. Meanwhile, the DAPT groups were treated with DAPT twice a week. Additionally, OSCs were also isolated after modeling, and then treated with drug serum containing ZGP or EV. Ovarian volume and the ratio of weight of total ovaries to the body weight were measured. The serum hormones were measured by ELISA. Quantities and location of OSCs in ovaries were detected by flow cytometry and immunofluorescence. Cell viability was measured by CCK8. And OSCs were identified by immunofluorescence. Biomarkers of germ cells, stem cells and associated to differentiation and meiosis were detected by qPCR and western blot. Proteins in Notch signaling pathway were detected by western blot and immunofluorescence. RESULTS: After treating with ZGP, ovarian volume and the ratio of weight of total ovaries to the body weight increased. ZGP could increase serum AMH and E2 level and decrease serum FSH level. Quantities and cell viability of OSCs increased after ZGP treatment in vivo and in vitro. In addition, treatment with ZGP could increase not only the expression of MVH, Oct4 and DAZL, but also the expression of ZP1 and ZP2. Furthermore, ZGP could up-regulate the expression of Notch intracellular domain (NICD), HES1 and HES5. After blocking the Notch signaling pathway, ZGP could increase not only the expression of NICD, HES1 and HES5, but also the expression of MVH, Oct4, DAZL, ZP1 and ZP3. CONCLUSION: In conclusion, the mechanism of ZGP on treating ovarian aging may be relevant to maintain the stemness of OSCs by up-regulating Notch signaling pathway, which added the mechanism of ZGP on the perspective of OSCs at first time.

Mechanical forces on trophoblast motility and its potential role in spiral artery remodeling during pregnancy.

During the first trimester of pregnancy, cytotrophoblasts (CTBs) differentiate into extravillous trophoblasts (EVTs). EVTs migrate from villus to decidua, invade maternal spiral arteries (SAs) and more strikingly, they migrate against blood flow along the vessels and replace endothelial cells (ECs), completing SA remodeling. Studies have indicated that trophoblast cells are mechanosensitive. They assemble ECs, which can align in the direction of fluid flow. However, how they sense blood flow and transform mechanical stimulations into chemical signals remain largely unexplored. What factors trigger their motility? what are the potential and major factors that guide them to find their path and empower them to migrate against flow? To answer these intricate questions, this review provides some of the novel aspects and sheds new insights into clinical applications.

Research on the Mechanism of Asperosaponin VI for Treating Recurrent Spontaneous Abortion by Bioinformatics Analysis and Experimental Validation.

Asperosaponin VI (AS6), as the quality marker of Dipsaci Radix, is verified to exert therapeutic effect on alleviating recurrent spontaneous abortion (RSA). However, due to the lack of relevant research, its molecular mechanism is still unclear. We retrieved targets for AS6 and RSA, and then used their overlapped targets for PPI analysis. In addition, we used GO and KEGG enrichment analyses, and molecular docking to investigate the anti-RSA mechanisms of AS6. Furthermore, we conducted in vitro experiments to validate the predictions of network pharmacology. Results showed that a total of 103 AS6-associated targets and 2084 RSA-associated targets, with 49 targets overlapped. GO enrichment analysis showed 845 significant biological processes like decidualization, while KEGG pathway enrichment analysis revealed 76 significant entries including 18 signaling pathways, which were closely linked to PI3K-Akt, HIF-1, TNF, IL-17, and VEGF signaling pathways, etc. Molecular docking findings verified that AS6 had tight link with the key targets including JUN, CASP3, STAT3, SRC, and PTGS2. Notably, in vitro experiments revealed that AS6 treatment could exert lower expressions of JUN, pro-CASP3, CASP3, STAT3, SRC, and PTGS2 in decidual cells compared with progesterone despite the expressions of STAT3, SRC, and PTGS2 with no significant difference, and mifepristone could interfere with the effects. In general, numerous targets and multiple pathways involve during the process of AS6 treatment against RSA. Moreover, our in vitro research first reported that AS6 may regulate the expressions of key targets (JUN, CASP3, STAT3, SRC, and PTGS2) in decidual cells to promote decidualization, thus treating RSA.

[Kidney-tonifying and abortion preventing effects of Shou Tai Wan by different extration methods on rats].

OBJECTIVE: To explore the Kidney-tonifying and abortion preventing effect of Shou Tai Wan (STW) by different extration methods on the SD Rats' abortion model. METHODS: Applied hydroxycarbamide and mifepristone (RU-486) to establish the abortion model of corpus luteum inhibition due to Kidney deficiency (disease-syndorme combination model) on SD, rats. Treated the model rats with STW formula. Observed the uterus condition and recorded the embryo number and the miscarriage rate of each rat. 4 kinds of extractions including water extract of STW (A liquid), alcohol extract of STW (B liquid), after the ethanol water extract residue of STW (C liquid) and B + C liquid. Visual observed the uterine lesions embryos and calculated obortion rate. Used chemluninescence methed to cheek the serum estradiol (E2) and progesterone (P) level. Used quantitative RT-PCR (qRT-PCR) to analyze the different of the PR mRNR between the model group and the treated group. RESULTS: Compared with the model group, the abortion rate of B + C liquid was greatly deduced and the embryo number of B + C liquid group, the E2 and P levels were obviously increased in the treated groups. CONCLUSION: STW (B + C) has the best effect of tonifying the kidney and preventing abortion.

Development of a Novel Nomogram for Predicting Premature Rupture of Membrane in Pregnant Women With Vulvovaginal Candidiasis.

Objective: The aim of this study was to develop a nomogram to predict the risk of premature rupture of membrane (PROM) in pregnant women with vulvovaginal candidiasis (VVC). Patients and methods: We developed a prediction model based on a training dataset of 417 gravidas with VVC, the data were collected from January 2013 to December 2020. The least absolute shrinkage and selection operator regression model was used to optimize feature selection for the model. Multivariable logistic regression analysis was applied to build a prediction model incorporating the feature selected in the least absolute shrinkage and selection operator regression model. Discrimination, calibration, and clinical usefulness of the prediction model were assessed using the C-index, calibration plot, and decision curve analysis. Internal validation was assessed using bootstrapping validation. Results: Predictors contained in the prediction nomogram included age, regular perinatal visits, history of VVC before pregnancy, symptoms with VVC, cured of VVC during pregnancy, and bacterial vaginitis. The model displayed discrimination with a C-index of 0.684 (95% confidence interval: 0.631-0.737). Decision curve analysis showed that the PROM nomogram was clinically useful when intervention was decided at a PROM possibility threshold of 13%. Conclusion: This novel PROM nomogram incorporating age, regular perinatal visits, history of VVC before pregnancy, symptoms with VVC, cured of VVC during pregnancy, and bacterial vaginitis could be conveniently used to facilitate PROM risk prediction in gravidas.