231 research outputs found

    Analysis of risk factors for recurrence in infertile endometrial cancer patients after in vitro fertilization treatment

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    PurposeTo investigate the oncologic outcomes of patients with early-stage endometrioid endometrial cancer (EEC) treated with in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) following fertility-sparing treatment (FST).MethodsA total of 62 patients who underwent IVF/ICSI treatment in a single fertility center between June 2010 and December 2021 after conservative treatment for early-stage EEC were assigned to a recurrence group and a non-recurrence group. Their clinical characteristics and disease outcomes were retrospectively evaluated.ResultsThe 62 women with complete remission (CR) after FST for EEC underwent 103 IVF cycles, resulting in 41 fresh embryo transfers (ETs) and 70 frozen–thawed transfers; 27 (43.55%) achieved clinical pregnancies, and 20 (32.26%) gave birth to a total of 23 live neonates. Additionally, nine patients had live births from natural pregnancies after IVF failure, bringing the cumulative live birth rate to 46.77% (29/62). After a median follow-up period of 53.88 months (range 20.2–127.5 months), 17 patients (27.42%) experienced recurrence within 2.8 to 57.9 months after the first controlled ovarian stimulation (COS). The probability of relapse at 1, 2, and 3 years after the initiation of COS was 14.52% (9/62), 21% (13/62), and 25.81% (16/62), respectively. Factors such as the time to CR, the time to IVF, the frequency of COS, maintenance treatment before IVF, and histology type were not found to significantly affect recurrence (p = 0.079, 0.182, 0.093, 0.267, and 0.41, respectively). Live births (hazard ratio (HR): 0.28, 95% CI: 0.082–0.962, p = 0.043) and the protocol of letrozole plus gonadotropin-releasing hormone (GnRH) antagonist/agonist used during IVF (HR: 0.1, 95% CI: 0.011–0.882, p = 0.038) were identified as independent favorable factors for recurrence.ConclusionsLive birth was associated with decreased recurrence of EEC. Reducing estrogen levels during COS may serve to mitigate the risk of endometrial cancer recurrence

    Estrogenic modulation of uropathogenic Escherichia coli infection pathogenesis in a murine menopause model

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    Recurrent urinary tract infections (UTIs), primarily caused by uropathogenic Escherichia coli (UPEC), annually affect over 13 million patients in the United States. Menopausal women are disproportionally susceptible, suggesting estrogen deficiency is a significant risk factor for chronic and recurrent UTI. How estrogen status governs susceptibility to UTIs remains unknown, and whether hormone therapy protects against UTIs remains controversial. Here, we used a mouse model of surgical menopause by ovariectomy and demonstrate a protective role for estrogen in UTI pathogenesis. We found that ovariectomized mice had significantly higher bacteriuria, a more robust inflammatory response, and increased production of the proinflammatory cytokine interleukin-6 (IL-6) upon UPEC infection compared to sham-operated controls. We further show that response of the urothelial stem cell niche to infection, normally activated to restore homeostasis after infection, was aberrant in ovariectomized mice with defective superficial urothelial cell differentiation. Finally, UPEC-infected ovariectomized mice showed a significant increase in quiescent intracellular bacterial reservoirs, which reside in the urothelium and can seed recurrent infections. Importantly, this and other ovariectomy-induced outcomes of UTI were reversible upon estrogen supplementation. Together, our findings establish ovariectomized mice as a model for UTIs in menopausal women and pinpoint specific events during course of infection that are most susceptible to estrogen deficiency. These findings have profound implications for the understanding of the role of estrogen and estrogen therapy in bladder health and pathogen defense mechanisms and open the door for prophylaxis for menopausal women with recurrent UTIs

    Reproductive Outcomes of In Vitro Fertilization and Fresh Embryo Transfer in Infertile Women With Adenomyosis: A Retrospective Cohort Study

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    BackgroundAdenomyosis is commonly encountered in infertile women; however, it is still unclear whether adenomyosis has a detrimental effect on in vitro fertilization and embryo transfer (IVF-ET) outcomes.MethodWe enrolled 1146 patients with adenomyosis and 1146 frequency-matched control women in a 1:1 ratio based on age, BMI, and basal follicle-stimulating hormone (FSH) level. After controlling for other factors, the rates of clinical pregnancy, miscarriage, live birth, and obstetric complications were compared between two groups.ResultsThere was no significant difference in clinical pregnancy rate between the two groups (38.1% vs. 41.6%; P=0.088). The implantation rate (25.6% versus 28.6%, P=0.027) and live birth rate (26% versus 31.5%, P=0.004) were significantly lower in the women with adenomyosis than in the controls. The miscarriage rate in the adenomyosis group was higher than that in the control group (29.1% versus 17.2%, P=0.001). After adjusting for confounding factors, multivariate analysis showed the clinical pregnancy rate was not statistically different between the two groups (OR: 0.852, P=0.070). In the adenomyosis group, the rate of miscarriage(OR: 1.877, P=0.000), placenta previa (OR: 2.996, P=0.042)and preeclampsia (OR: 2.287, P=0.042)were increased significantly, while live birth rate (OR: 0.541, P=0.000) was reduced significantly than control group.ConclusionAdenomyosis has negative effect on IVF-ET outcomes in which miscarriage risk increased, live birth rate reduced and obstetric complications increased

    PpNAC187 Enhances Lignin Synthesis in ‘Whangkeumbae’ Pear (Pyrus pyrifolia) ‘Hard-End’ Fruit

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    A disorder in pears that is known as ‘hard-end’ fruit affects the appearance, edible quality, and market value of pear fruit. RNA-Seq was carried out on the calyx end of ‘Whangkeumbae’ pear fruit with and without the hard-end symptom to explore the mechanism underlying the formation of hard-end. The results indicated that the genes in the phenylpropanoid pathway affecting lignification were up-regulated in hard-end fruit. An analysis of differentially expressed genes (DEGs) identified three NAC transcription factors, and RT-qPCR analysis of PpNAC138, PpNAC186, and PpNAC187 confirmed that PpNAC187 gene expression was correlated with the hard-end disorder in pear fruit. A transient increase in PpNAC187 was observed in the calyx end of ‘Whangkeumbae’ fruit when they began to exhibit hard-end symptom. Concomitantly, the higher level of PpCCR and PpCOMT transcripts was observed, which are the key genes in lignin biosynthesis. Notably, lignin content in the stem and leaf tissues of transgenic tobacco overexpressing PpNAC187 was significantly higher than in the control plants that were transformed with an empty vector. Furthermore, transgenic tobacco overexpressing PpNAC187 had a larger number of xylem vessel elements. The results of this study confirmed that PpNAC187 functions in inducing lignification in pear fruit during the development of the hard-end disorder. View Full-Tex

    Implications of C1q/TNF-related protein superfamily in patients with coronary artery disease.

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    The C1q complement/TNF-related protein superfamily (CTRPs) displays differential effects on the regulation of metabolic homeostasis, governing cardiovascular function. However, whether and how they may serve as predictor/pro-diagnosis factors for assessing the risks of coronary artery disease (CAD) remains controversial. Therefore, we performed a clinical study to elaborate on the implication of CTRPs (CTRP1, CTRP5, CTRP7, and CTRP15) in CAD. CTRP1 were significantly increased, whereas CTRP7 and CTRP15 levels were decreased in CAD patients compared to the non-CAD group. Significant differences in CTRP1 levels were discovered between the single- and triple-vascular-vessel lesion groups. ROC analysis revealed that CTRP7 and CTRP15 may serve as CAD markers, while CTRP1 may serve as a marker for the single-vessel lesion of CAD. CTRP1 and CTRP5 can serve as markers for the triple-vessel lesion. CTRP1 may serve as an independent risk predictor for triple-vessel lesion, whereas CTRP15 alteration may serve for a single-vessel lesion of CAD. CTRP1 may serve as a novel superior biomarker for diagnosis of severity of vessel-lesion of CAD patients. CTRP7, CTRP15 may serve as more suitable biomarker for the diagnosis of CAD patients, whereas CTRP5 may serve as an independent predictor for CAD. These findings suggest CTRPs may be the superior predictive factors for the vascular lesion of CAD and represent novel therapeutic targets against CAD

    Heterogeneous Vancomycin-Intermediate Staphylococcus aureus Uses the VraSR Regulatory System to Modulate Autophagy for Increased Intracellular Survival in Macrophage-Like Cell Line RAW264.7

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    The VraSR two-component system is a vancomycin resistance-associated sensor/regulator that is upregulated in vancomycin-intermediate Staphylococcus aureus (VISA) and heterogeneous VISA (hVISA) strains. VISA/hVISA show reduced susceptibility to vancomycin and an increased ability to evade host immune responses, resulting in enhanced clinical persistence. However, the underlying mechanism remains unclear. Recent studies have reported that S. aureus strains have developed some strategies to survive within the host cell by using autophagy processes. In this study, we confirmed that clinical isolates with high vraR expression showed increased survival in murine macrophage-like RAW264.7 cells. We constructed isogenic vraSR deletion strain Mu3ΔvraSR and vraSR-complemented strain Mu3ΔvraSR-C to ascertain whether S. aureus uses the VraSR system to modulate autophagy for increasing intracellular survival in RAW264.7. Overall, the survival of Mu3ΔvraSR in RAW264.7 cells was reduced at all infection time points compared with that of the Mu3 wild-type strain. Mu3ΔvraSR-infected RAW264.7 cells also showed decreased transcription of autophagy-related genes Becn1 and Atg5, decreased LC3-II turnover and increased p62 degradation, and fewer visible punctate LC3 structures. In addition, we found that inhibition of autophagic flux significantly increased the survival of Mu3ΔvraSR in RAW264.7 cells. Together, these results demonstrate that S. aureus uses the VraSR system to modulate host-cell autophagy processes for increasing its own survival within macrophages. Our study provides novel insights into the impact of VraSR on bacterial infection and will help to further elucidate the relationship between bacteria and the host immune response. Moreover, understanding the autophagic pathway in vraSR associated immunity has potentially important implications for preventing or treating VISA/hVISA infection

    Presenilin-Dependent Receptor Processing Is Required for Axon Guidance

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    SummaryThe Alzheimer's disease-linked gene presenilin is required for intramembrane proteolysis of amyloid-β precursor protein, contributing to the pathogenesis of neurodegeneration that is characterized by loss of neuronal connections, but the role of Presenilin in establishing neuronal connections is less clear. Through a forward genetic screen in mice for recessive genes affecting motor neurons, we identified the Columbus allele, which disrupts motor axon projections from the spinal cord. We mapped this mutation to the Presenilin-1 gene. Motor neurons and commissural interneurons in Columbus mutants lacking Presenilin-1 acquire an inappropriate attraction to Netrin produced by the floor plate because of an accumulation of DCC receptor fragments within the membrane that are insensitive to Slit/Robo silencing. Our findings reveal that Presenilin-dependent DCC receptor processing coordinates the interplay between Netrin/DCC and Slit/Robo signaling. Thus, Presenilin is a key neural circuit builder that gates the spatiotemporal pattern of guidance signaling, thereby ensuring neural projections occur with high fidelity

    The influence of timing of oocytes retrieval and embryo transfer on the IVF-ET outcomes in patients having bilateral salpingectomy due to bilateral hydrosalpinx

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    ObjectiveThe objective of the study was to investigate whether the sequence of oocyte retrieval and salpingectomy for hydrosalpinx affects pregnancy outcomes of in vitro fertilization and embryo transfer (IVF-ET) patients.Study DesignThere were 1,610 bilateral hydrosalpinx patients who underwent laparoscopy salpingectomy and IVF-ET/intracytoplasmic sperm injection (ICSI) from January 2009 to December 2018. They were divided into two groups: oocyte retrieval first group: 235 accepted oocyte retrieval before salpingectomy; operation first group: 1,375 accepted oocyte retrieval after salpingectomy. The basic information and pregnancy outcomes of the two groups were compared. The pregnancy outcomes and influencing factors were analyzed among patients at different starting times of frozen-thawed embryo transfer (FET) or oocyte retrieval after the salpingectomy.ResultsPatients in the oocyte retrieval first group had higher levels of basal follicle stimulating hormone and lower anti-Mullerian hormone levels (P < 0.05). There were no cases of pelvic infection or oocyte and embryo contamination after oocyte retrieval in the oocyte retrieval first group. In the frozen cycle, the clinical pregnancy and miscarriage rates of the oocyte retrieval first group were lower than those in the operation first group (P < 0.05), while the live birth rate was not significantly different (P > 0.05). The live birth rates of patients ≥35 years old in the operation first group and the oocyte retrieval first group were not significantly different (29.3% vs. 23.3%, P = 0.240). After adjusting for age and antral follicle count (AFC), oocyte retrieval 4–6 and 7–12 months after the operation had higher accumulated pregnancy rates [OR 1.439 (1.045–1.982), P = 0.026; OR 1.509 (1.055–2.158), P = 0.024] and higher accumulated live birth rates [OR 1.419 (1.018–1.977), P = 0.039; OR 1.544 (1.068–2.230), P = 0.021]. No significant difference was observed in the pregnancy outcomes of frozen embryo transfer at different times after salpingectomy (P > 0.05).ConclusionNo contamination of the embryo or infection was observed in patients who underwent oocyte retrieval before the operation. The interval between the operation and frozen embryo transfer did not affect the pregnancy outcomes. After adjusting for age and AFC, patients who underwent oocyte retrieval 4–6 and 7–12 months after the operation had higher accumulated pregnancy rates and live birth rates
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