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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., (© 2024 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Long non-coding RNA (lncRNA) anomalies cause early ovarian failure. LncRNA nuclear enriched abundant transcript 1 (NEAT1) was down-regulated in premature ovarian failure (POF) mice and connected to the illness, however, the mechanism remained unclear. The levels of gene and protein were measured by using quantitative real-time polymerase chain reaction, Western blot, and immunofluorescence. Follicle stimulating hormone (FSH), estradiol (E2), and luteinizing hormone (LH) levels were determined using enzyme-linked immunosorbent assay (ELISA). 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and flow cytometry were used to determine cell viability and apoptosis. The interaction of NEAT1, miR-654, and stanniocalcin-2 (STC2) was verified by dual-luciferase reporter assay or RNA binding protein immunoprecipitation (RIP) assays. The results showed NEAT1 and STC2 down-regulated, while miR-654 up-regulated in POF mice. Overexpression of NEAT1 reduced apoptosis and autophagy in cyclophosphamide (CTX)-treated ovarian granulosa cells (OGCs), and Bax, cleaved-caspase3, LC3B, LC3II/LC3I ratio were decreased and Bcl-2 and p62 were raised. NEAT1 suppressed miR-654 expression by directly targeting miR-654. The inhibition of NEAT1 overexpression on apoptosis and autophagy in OGCs was reversed by miR-654 mimics. STC2 was a target gene of miR-654, and miR-654 inhibitor reduced the apoptosis and autophagy by regulating the STC2/MAPK axis. To sum up, NEAT1 reduced miR-654 expression and modulated the STC2/MAPK pathway to decrease apoptosis and autophagy in POF, indicating a potential therapeutic target., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Endometrial carcinoma (EC) is a kind of fatal female malignancy. lncRNA GATA3-AS1 has been identified as an oncogene in various cancers. However, the functions and mechanisms of GATA3-AS1 in EC remain to be explored. Human EC tissues and four EC cell lines were used. Western blotting and quantitative real-time PCR (qRT-PCR) were used to evaluate the expression of GATA3-AS1, miR-361, and ARRB2. Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were used to validate the interaction among GATA3-AS1, miR-361, and ARRB2. Flow cytometry, colony formation assay, scratch assay, and transwell assay were used to examine the cell apoptosis, proliferation, migration, and invasion of EC cells, respectively. In vivo tumor growth was monitored in nude mice. GATA3-AS1 and ARRB2 were upregulated while miR-361 was downregulated in human EC tissues and EC cells. GATA3-AS1 knockdown constrained cell proliferation, invasion, migration, and EMT while promoting the apoptosis of EC cells by upregulating miR-361. GATA3-AS1 negatively regulated miR-361 expression. ARRB2 was the direct target of miR-361 and could activate the Src/Akt pathway. In vivo, GATA3-AS1 knockdown suppressed tumor progression by upregulating the miR-361 expression. lncRNA GATA3-AS1 promoted EC invasion and migration by the miR-361/ARRB2 axis, which indicated that GATA3-AS1 might be a promising therapeutic option for advanced EC progression. KEY MESSAGES: GATA3-AS1 knockdown suppressed EC proliferation, invasion, and migration. GATA3-AS1 directly inhibited miR-361 as a ceRNA. MiR-361 knockdown reversed the tumor suppressive effect caused by GATA3-AS1 knockdown. MiR-361 bound to ARRB2 directly and suppressed its expression. The GATA3-AS1/miR-361/ARRB2 axis regulated EC cell proliferation, invasion, and migration., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: The aim of this study was to evaluate white blood cell (WBC) count as a risk factor related to methotrexate (MTX) treatment failure in patients with ectopic pregnancy (EP). Methods: A total of 236 women diagnosed with EP and treated with a single dose of MTX were included. The exposure variable was WBC count at baseline, and the outcome was MTX treatment outcome. Both a multivariate binary logistics regression model and subgroup analysis were performed to evaluate the association between WBC and MTX non-response. Results: WBC count was associated with the risk of treatment failure, and the odds ratio (OR) in different multivariate models was stable [minimally adjusted model: OR 1.2, 95% confidence interval (CI): 1.0-1.3, p = 0.008; fully adjusted model: OR 1.2, 95% CI: 1.0-1.4, p = 0.026]. For WBCs in group T3 (>8.9 × 109/L), the association between WBC count and treatment failure was significant (minimally adjusted model: OR: 2.0, 95% CI: 1.0-3.8, p = 0.050; fully adjusted model: OR: 2.2, 95% CI: 1.1-5.6, p = 0.034). Subgroup analysis showed that in participants with regular menstruation (OR 1.1, 95% CI: 1.0-1.3), WBC count was significantly different from irregular menstruation (OR 1.8, 95% CI: 1.2-2.8); p for interaction was 0.031. Conclusions: We found a reliable and non-linear relationship between WBC count and MTX treatment failure for EP., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chen, Chen, Qiu, Huang, Deng and Gao.)

The features of the vaginal microbiota (VM) community can reflect health status, and they could become new biomarkers for disease diagnosis. During pregnancy, domination of bacteria of the genus Lactobacillus in the VM community is regarded as a keystone because they stabilize the VM by producing antimicrobial compounds and competing adhesion. An altered VM composition provides a marker for adverse pregnancy outcomes. This nested case-control study aimed to characterize the VM in women with a tubal pregnancy (TP) presenting with pain and/or uterine bleeding in early pregnancy. Chinese women with a symptomatic early pregnancy of unknown location were the study cohort. 16S rDNA gene-sequencing of V3-V4 variable regions was done to assess the diversity, structures, taxonomic biomarkers, and classification of the VM community. The primary outcome was the location of the early pregnancy. The VM community in women with a TP showed higher diversity (PD-whole-tree, median: 8.26 vs . 7.08, P = 0.047; Shannon Diversity Index, median: 1.43 vs 0.99, P = 0.03) and showed different structures to those in women with an intrauterine pregnancy (IUP) ( R = 0.23, P < 0.01). Bacteria of the genus Lactobacillus were significantly enriched in the IUP group, whereas bacteria of the genera Gardnerella and Prevotella were significantly enriched in the TP group. Lactobacillus abundance could be used to classify the pregnancy location (AUC = 0.81). Non- Lactobacillus -dominated microbiota (≤ 0.85% Lactobacillus ) was significantly associated with a TP (adjusted odds ratio: 4.42, 95% confidence interval: 1.33 to 14.71, P = 0.02). In conclusion, among women with a symptomatic early pregnancy, a higher diversity and lower abundance of Lactobacillus in the VM is associated with a TP., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ruan, Zhang, Chen, Liu, Zhu, Huang, Liu, Luo, Deng and Gao.)

To explore the medication rules of famous veteran traditional Chinese medicine practitioners in treating infertility based on medical cases of infertility collected from book series of Hundred Traditional Chinese Medicine Clinicians of Hundred Years in China and Prescription Proven by Traditional Chinese Medicine Masters. Researchers extracted the information of prescriptions from these cases according to the inclusion and exclusion criteria. Then, Excel 2010, SPSS Clementine(ver.12.0) and SPSS(ver. 22.0) were adopted respectively for frequency analysis, association rules analysis, cluster analysis and factor analysis. Cluster analysis was carried out by Ochiai algorithm of binary variable data, which was a systematic clustering method. And principal component analysis was used for factor analysis. Besides, KMO test and Bartlett spherical test were used for factor adaptation test. Finally, 151 medical cases and 396 prescriptions were included in total. A total of 60 kinds of frequently used herbs were identified according to the results of frequency analysis for medication, they were mainly used for activating blood and resolving stasis, tonifying and clearing heat respectively. The association rules analysis found out 25 drug pair association rules and 14 3-drug combination association rules. A total of 15 medicine groups were extracted by cluster analysis. KMO test and Bartlett spherical test indicated that the method was suitable for factor analysis, and 21 common factors were respectively extracted by factor analysis. Association rules indicated the characteristics of the therapeutic methods, like tonifying Qi and replenishing blood. The famous veteran traditional Chinese medicine practitioners utilized modified Siwu Decoction for tonifying blood and preferred Atractylodis Macrocephalae Rhizoma(Baizhu) for tonifying Qi. The results of both cluster analysis and factor analysis demonstrated the characteristics of the therapies for tonifying kidney, activating blood, tonifying spleen and dispelling dampness. In addition, factor analysis could reflect the therapies for nourishing Yin, tonifying kidney, warming the meridian, dissipating cold, nourishing blood and dispelling blood stasis. These results of analysis comprehensively showed out the medication characteristics of famous veteran traditional Chinese medicine practitioners of strictly following the pathogenesis, making good use of classical formulas and providing proper compatibility. In conclusion, data mining techniques(including frequency analysis, association rules analysis, cluster analysis and factor analysis) were used to comprehensively analyze the medication rules of famous veteran traditional Chinese medicine practitioners in treating infertility, which is helpful for guiding the clinical practice of treating infertility with traditional Chinese medicine.

Objective: To evaluate the efficacy, bleeding profile and safety of low-dose levonorgestrel-releasing intrauterine system (LNG-IUS 8) in Chinese healthy women of childbearing age. Methods: A multi-center, open-label, single-arm clinical trial conducted at 16 centres in China enrolled 773 healthy women of childbearing age (mean age 31.6 years old, range 18 to 40 years old) , who demanded contraception, from April 2006 to June 2013. All women placed LNG-IUS 8 for 3 years and then been followed up at 3, 6, 9, 12, 18, 24, 30, 36 months. The efficacy variables including pregnancy rate and expulsion rate were analyzed using life table, while observing adverse events (AE) to evaluate the safety. The bleeding profile happened during the study was assessed using 90-day reference intervals (World Health Organization criteria) . Results: Eight pregnancies occurred among 773 women, resulting in a overall Pearl index of 0.42 per 100 women years. The 3-year cumulative pregnancy rate was 0.37 per 100 women years and the 3-year cumulative expulsion rate was 1.99 per 100 women years. The number of women with bleeding/spotting reduced and the bleeding/spotting days declined over time. Totally 219 AE were reported related to LNG-IUS 8 placements. The most common AE were vaginal bleeding (8.2%, 63/773) and the ovarian cyst (6.2%, 52/773) . LNG-IUS 8 had an improving effect on dysmenorrhea that the percentage of women with dysmenorrhea as well as the days of dysmenorrhea decreased over time. The percentage of women satisfied or very satisfied with LNG-IUS 8 was 87.2% (622/713) . Conclusion: LNG-IUS 8 is highly effective and safe for Chinese healthy women of childbearing age.

Interventional therapy is characterized by mini-invasion, accuracy, obvious curative effect and little side effect. In China, interventional therapy has been applied widely in the treatment of malignant carcinoma in recent 10 years. Traditional Chinese medicine (TCM) also has been adopted in the interventional therapy in recent years. This article reviews the history, status quo and prospect in interventional treatment of carcinoma with traditional Chinese medicine in experimental and clinical domains in recent years. Interventional therapy combined with TCM preparation directly or TCM therapy as a supplementary method of interventional therapy for carcinoma has played an active role in improving clinical curative effect, controlling and reducing toxic side effect and complications.