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Whole genome doubling (WGD) has been found to be associated with an early onset of adenomyosis (AM) and a higher response rate to endocrine therapy. The study analyzed the genomic and transcriptomic characteristics of endometrium from AM and endometriosis (EM) patients. WGD was detected in 33 samples from 29 patients, and it was significantly associated with a younger age at AM onset. However, no specific gene mutations were found to be relevant to the occurrence or clinical manifestation of WGD in AM. [Extracted from the article]

IntroductionEpidemiological studies have suggested that dietary factors, especially high consumption of high glycaemic index carbohydrates and sugars, may trigger or exacerbate the progression of type 1 diabetes. We aimed to provide experimental evidence to confirm this relevance and to explore the underlying mechanisms.MethodsNOD mice were given sustained high-glucose drinking or glucose-free water and observed for the incidence of type 1 diabetes and islet inflammation. RNAseq was performed to detect the transcriptome changes of the NOD islet beta cell line NIT-1 after high glucose treatment, and mass spectrometry was performed to detect the proteome changes of NIT-1-cells-derived sEVs.ResultsSustained high glucose drinking significantly aggravates islet inflammation and accelerates the onset of type 1 diabetes in NOD mice. Mechanistically, high glucose treatment induces aberrant ER stress and up-regulates the expression of autoantigens in islet beta cell. Moreover, high glucose treatment alters the proteome of beta-cells-derived sEVs, and significantly enhances the ability of sEVs to promote DC maturation and stimulate immune inflammatory response.DiscussionThis study provides evidence for negative effect of high glucose intake as a dietary factor on the pathogenesis of type 1 diabetes in genetically predisposed individuals. Therefore, avoiding high sugar intake may be an effective disease prevention strategy for children or adults susceptible to type 1 diabetes.

Background: Long‐term immunosuppressive maintenance therapy is necessary to prevent the rejection of xenografts. However, it is still unclear which oral immunosuppressant is most suitable for pig‐to‐human xenotransplantation. Methods: A xenogeneic mixed lymphocyte reaction (MLR) system was established using peripheral blood mononuclear cells (PBMCs) isolated from wildtype (WT) or GTKO/CMAHKO/β4GalNT2KO (TKO) pigs as stimulator cells and human PBMCs as responder cells. Various concentrations of tacrolimus (Tac), cyclosporine (CsA), or rapamycin (Rapa) were added to the MLR system as interventions. The inhibitory effects of the three immunosuppressants on the proliferation and cytokine production of human T cells were studied and compared. The inhibitory effect of anti‐CD154 mAb alone or in combination with Tac/CsA/Rapa on xenoreactive MLR was also investigated. Results: PBMCs from both WT and TKO pigs stimulated significant proliferation of human T cells. Tac had a strong inhibitory effect on human T‐cell proliferation stimulated by pig PBMCs. CsA inhibited human T‐cell proliferation in a typical dose‐dependent manner. When Tac and CsA concentrations reached 5 and 200 ng/mL, respectively, the proliferation rates of CD3+/CD4+/CD8+ T cells were reduced almost to a negative level. Even at high concentrations, Rapa had only a moderate inhibitory effect on xenogeneic MLR. The inhibitory effects of these three immunosuppressants on xenogeneic T‐cell responses were further confirmed by the detection of CD25 expression and supernatant cytokines (IL‐2, IL‐6, IFN‐γ, TNF‐α, IL‐4, IL‐10, and IL‐17). Although anti‐CD154 mAb monotherapy showed only moderate inhibitory effects on xenoreactive T‐cell proliferation, low‐dose anti‐CD154 mAb combined with low‐dose Tac, CSA, or Rapa could produce significant synergistic inhibitory effects. Conclusion: Tac is more efficient than CsA or Rapa in inhibiting xenogeneic T‐cell responses in vitro. If used in combination with anti‐CD154 mAb, all the three immunosuppressants can achieve satisfactory synergistic inhibitory effects. [ABSTRACT FROM AUTHOR]

Objective: To assess pelvic floor muscle (PFM) strength and influencing factors among healthy women at different life stages. Design: Multicentre cross‐sectional study. Setting: Fourteen hospitals in China. Population: A total of 5040 healthy women allocated to the following groups (with 1680 women per group): premenopausal nulliparous, premenopausal parous and postmenopausal. Methods: The PFM strength was evaluated by vaginal manometry. Multivariate logistic regression was used to determine the influencing factors for low PFM strength. Main Outcome Measures: Maximum voluntary contraction pressure (MVCP). Results: The median MVCP values were 36, 35 and 35 cmH2O in premenopausal nulliparous (aged 19–51 years), premenopausal parous (aged 22–61 years), and postmenopausal (aged 40–86 years) women, respectively. In the premenopausal nulliparous group, physical work (odds ratio, OR 2.05) was the risk factor for low PFM strength, which may be related to the chronic increased abdominal pressure caused by physical work. In the premenopausal parous group, the number of vaginal deliveries (OR 1.28) and diabetes (OR 2.70) were risk factors for low PFM strength, whereas sexual intercourse (<2 times per week vs. none, OR 0.55; ≥2 times per week vs. none, OR 0.56) and PFM exercise (OR 0.50) may have protective effects. In the postmenopausal group, the number of vaginal deliveries (OR 1.32) and family history of pelvic organ prolapse (POP) (OR 1.83) were risk factors for low PFM strength. Conclusions: Physical work, vaginal delivery, diabetes and a family history of POP are all risk factors for low PFM strength, whereas PFM exercises and sexual life can have a protective effect. The importance of these factors varies at different stages of a woman's life. [ABSTRACT FROM AUTHOR]