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Sichuan Da Xue Xue Bao. Yi Xue Ban =... May 2024This study aims to analyze the relationship between reproductive tract microecological changes, metabolic differences, and pregnancy outcomes at different time points in...
OBJECTIVE
This study aims to analyze the relationship between reproductive tract microecological changes, metabolic differences, and pregnancy outcomes at different time points in the frozen-thawed embryo transfer cycle while patients are undergoing hormone replacement therapy, which will be a breakthrough point for improving outcomes.
METHODS
A total of 20 women undergoing frozen-thawed single blastocyst transfer for the first time at the Reproductive Medicine Center of Fujian Maternal and Child Health Hospital between July 2022 and January 2023 were recruited for this study. Their vaginal and cervical secretions were collected for 16S rRNA sequencing and non-targeted metabolomics analysis on days 2-5 of menstruation, day 7 after estrogen replacement therapy started, the day when progesterone was added, and the day of transplantation. The subjects were divided into different groups according to their clinical pregnancy status and the sequencing results were analyzed using bioinformatics methods.
RESULTS
1) The alpha-diversity index of the vaginal and cervical microbiota was higher on days 2-5 of menstruation (<0.01), but did not differ significantly on day 7 after oral estrogen replacement therapy started, the day of progesterone administration, and the day of transplantation (≥0.1). 2) Both the pregnant group and the non-pregnant group showed a variety of microorganisms and metabolites with significant differences in the lower reproductive tract at different time points. 3) Microbial analysis at different time points showed that there were significant differences in vaginal flora, including , , , , , , , , , and in the pregnant group (<0.05). 4) Metabolite analysis at different time points showed that there were significant differences in 3-hydroxybenzoic acid, linatine, (R)-amphetamine, hydroxychloroquine, and L-altarate in the vaginal secretions of the pregnant group (<0.05), and that there were significant differences in isocitric acid, quassin, citrinin, and 12(R)-HETE in the cervical secretions (<0.05). 5) Metabolite analysis at different time points showed that, in the non-pregnant group, there were significant differences in linatine, decanoyl-L-carnitine, aspartame, sphingosine, and hydroxychloroquine in the vaginal secretions (<0.05), and the isocitric acid, quassin, ctrinin, and 12(R)-HETE in the cervical secretions (<0.05). 6) Combined microbiome and metabolomics analysis showed that certain metabolites were significantly associated with microbial communities, especially .
CONCLUSIONS
Significant differences in the microbiota genera and metabolites at different time points were found during the frozen-embryo transfer cycle of hormone replacement therapy, which may be used as potential biomarkers to predict pregnancy outcomes of embryo transfer.
Topics: Humans; Female; Pregnancy; Embryo Transfer; Pregnancy Outcome; Microbiota; Vagina; Progesterone; Adult; Cryopreservation; RNA, Ribosomal, 16S; Cervix Uteri
PubMed: 38948288
DOI: 10.12182/20240560509 -
World Journal of Stem Cells Jun 2024Pelvic organ prolapse (POP) involves pelvic organ herniation into the vagina due to pelvic floor tissue laxity, and vaginal structure is an essential factor. In POP, the...
BACKGROUND
Pelvic organ prolapse (POP) involves pelvic organ herniation into the vagina due to pelvic floor tissue laxity, and vaginal structure is an essential factor. In POP, the vaginal walls exhibit abnormal collagen distribution and decreased fibroblast levels and functions. The intricate etiology of POP and the prohibition of transvaginal meshes in pelvic reconstruction surgery present challenges in targeted therapy development. Human umbilical cord mesenchymal stromal cells (hucMSCs) present limitations, but their exosomes (hucMSC-Exo) are promising therapeutic tools for promoting fibroblast proliferation and extracellular matrix remodeling.
AIM
To investigate the effects of hucMSC-Exo on the functions of primary vaginal fibroblasts and to elucidate the underlying mechanism involved.
METHODS
Human vaginal wall collagen content was assessed by Masson's trichrome and Sirius blue staining. Gene expression differences in fibroblasts from patients with and without POP were assessed RNA sequencing (RNA-seq). The effects of hucMSC-Exo on fibroblasts were determined functional experiments . RNA-seq data from fibroblasts exposed to hucMSC-Exo and microRNA (miRNA) sequencing data from hucMSC-Exo were jointly analyzed to identify effective molecules.
RESULTS
In POP, the vaginal wall exhibited abnormal collagen distribution and reduced fibroblast 1 quality and quantity. Treatment with 4 or 6 μg/mL hucMSC-Exo suppressed inflammation in POP group fibroblasts, stimulated primary fibroblast growth, and elevated collagen I (Col1) production . High-throughput RNA-seq of fibroblasts treated with hucMSC-Exo and miRNA sequencing of hucMSC-Exo revealed that abundant exosomal miRNAs downregulated matrix metalloproteinase 11 (MMP11) expression.
CONCLUSION
HucMSC-Exo normalized the growth and function of primary fibroblasts from patients with POP by promoting cell growth and Col1 expression . Abundant miRNAs in hucMSC-Exo targeted and downregulated MMP11 expression. HucMSC-Exo-based therapy may be ideal for safely and effectively treating POP.
PubMed: 38948096
DOI: 10.4252/wjsc.v16.i6.708 -
Cureus May 2024Bilateral single-system ectopic ureters (BSSEUs) are among the rarest entities encountered in pediatric urology. A BSSEU occurs when the ureteric buds originate...
Bilateral single-system ectopic ureters (BSSEUs) are among the rarest entities encountered in pediatric urology. A BSSEU occurs when the ureteric buds originate cranially from the mesonephric ducts, causing a delay in their integration into the urogenital sinus. It presents as continuous incontinence in females, whereas symptoms like infection and discomfort are present in males. We describe a case involving a BSSEU opening into the vagina and urethra, with the patient experiencing continuous urinary incontinence, and its diagnosis and management. Here, We discuss a rare case of a four-year-old girl exhibiting continuous urinary incontinence or dribbling associated with recurrent urinary tract infections (UTIs) attributed to bilateral ectopic ureters. Imaging modalities, including contrast-enhanced computed tomography(CECT) and MRI, revealed the presence of BSSEUs accompanied by hydroureteronephrosis. The condition was managed with prompt surgical intervention involving bilateral ureteric reimplantation. Subsequent to the procedure, the patient experienced a significant improvement in continence mechanism and bladder capacity, obviating the requirement of urinary diversion procedure appendicovesicostomy or bladder neck reconstruction. Notably, while BSSEUs are an uncommon presentation, their timely and appropriate management is paramount in preventing potential renal damage. This case underscores the significance of vigilant monitoring and proactive intervention in addressing such complex urological anomalies in pediatric patients.
PubMed: 38947717
DOI: 10.7759/cureus.61341 -
Clinical Case Reports Jul 2024This was the first report of a pseudoaneurysm in a vaginal artery after hysterectomy, unlike other published studies that were of pseudoaneurysms in uterine or vaginal...
KEY CLINICAL MESSAGE
This was the first report of a pseudoaneurysm in a vaginal artery after hysterectomy, unlike other published studies that were of pseudoaneurysms in uterine or vaginal arteries after delivery.
ABSTRACT
A 51-year-old woman presented with massive vaginal bleeding 7 days after a hysterectomy, which caused hemoglobin to drop. The patient was suspicious of having a vaginal artery pseudoaneurysm according to the sonography. Her bleeding was stopped after the ligation of her left internal iliac artery.
PubMed: 38947543
DOI: 10.1002/ccr3.9006 -
MedRxiv : the Preprint Server For... Jun 2024Fine-mapping and gene-prioritisation techniques applied to the latest Genome-Wide Association Study (GWAS) results have prioritised hundreds of genes as causally...
Fine-mapping and gene-prioritisation techniques applied to the latest Genome-Wide Association Study (GWAS) results have prioritised hundreds of genes as causally associated with disease. Here we leverage these recently compiled lists of high-confidence causal genes to interrogate where in the body disease genes operate. Specifically, we combine GWAS summary statistics, gene prioritisation results and gene expression RNA-seq data from 46 tissues and 204 cell types in relation to 16 major diseases (including 8 cancers). In tissues and cell types with well-established relevance to the disease, the prioritised genes typically have higher absolute and relative (i.e. tissue/cell specific) expression compared to non-prioritised 'control' genes. Examples include brain tissues in psychiatric disorders (-value < 1×10), microglia cells in Alzheimer's Disease (-value = 9.8×10) and colon mucosa in colorectal cancer (-value < 1×10). We also observe significantly higher expression for disease genes in multiple tissues and cell types with no established links to the corresponding disease. While some of these results may be explained by cell types that span multiple tissues, such as macrophages in brain, blood, lung and spleen in relation to Alzheimer's disease (-values < 1×10), the cause for others is unclear and motivates further investigation that may provide novel insights into disease etiology. For example, mammary tissue in Type 2 Diabetes (-value < 1×10); reproductive tissues such as breast, uterus, vagina, and prostate in Coronary Artery Disease (-value < 1×10); and motor neurons in psychiatric disorders (-value < 3×10). In the GTEx dataset, tissue type is the major predictor of gene expression but the contribution of each predictor (tissue, sample, subject, batch) varies widely among disease-associated genes. Finally, we highlight genes with the highest levels of gene expression in relevant tissues to guide functional follow-up studies. Our results could offer novel insights into the tissues and cells involved in disease initiation, inform drug target and delivery strategies, highlighting potential off-target effects, and exemplify the relative performance of different statistical tests for linking disease genes with tissue and cell type gene expression.
PubMed: 38947033
DOI: 10.1101/2024.06.20.24309121 -
Research Square Jun 2024: Stem-cell-derived therapy is a promising option for tissue regeneration. Human iPSC-derived progenitors of smooth muscle cells (pSMCs) have limited proliferation and...
: Stem-cell-derived therapy is a promising option for tissue regeneration. Human iPSC-derived progenitors of smooth muscle cells (pSMCs) have limited proliferation and differentiation, which may minimize the risk of tumor formation while restoring smooth muscle cell deficiencies. Up to 30 % of women who suffer from recurrence of vaginal prolapse after prolapse surgery are faced with reoperation. Therefore, there is an unmet need for therapies that can restore vaginal tissue function. We hypothesize that human pSMCs can restore vaginal function in a vaginal-injury rat model. : Female immune-compromised RNU rats were divided into 5 groups: intact controls (n=12), VSHAM (surgery + saline injection, n=33), and cell-injection group (surgery + cell injection using three patient pSMCs lines, n=14/cell line). The surgery, similar to what is done in vaginal prolapse surgery, involved ovariectomy, urethrolysis, and vagina injury. The vagina, urethra, bladder dome and trigone were harvested 10 weeks after surgery (5 weeks after injection). Organ bath myography was performed to evaluate the contractile function of vagina, and smooth muscle thickness was examined by tissue immunohistochemistry. Collagen I, collagen III, and elastin mRNA and protein expressions in tissues were assessed. : When compared to the VSHAM group, cell-injection groups showed significantly increased vaginal smooth muscle contractions induced by carbachol (groups A and C) and by KCl (group C), and significantly higher collagen I protein expression in the vagina (groups A and B). Elastin mRNA and protein expressions in the vagina did not correlate with injection group. In the urethra, mRNA expressions of collagen I, collagen III, and elastin were all significantly higher in the cell-injection groups compared to the VSHAM group. Collagen I protein expression of the urethra was also higher in the cell-injection group compared to the VSHAM group. Elastin protein expression in the urethra did not correlate with injection group. : Human iPSC-derived pSMCs improved contractile function of the post-surgery vagina. Additionally, pSMC injection modulated collagen I, collagen III and elastin mRNA and protein expressions in the vagina and urethra. These findings suggest that pSMCs may be a possible therapy for vaginal prolapse recurrence after surgical intervention.
PubMed: 38946968
DOI: 10.21203/rs.3.rs-4172308/v1 -
Annals of Coloproctology Jun 2024Neoadjuvant imatinib treatment, followed by complete transvaginal removal, presents a feasible option for large rectal gastrointestinal tumors located on the anterior...
Neoadjuvant imatinib treatment, followed by complete transvaginal removal, presents a feasible option for large rectal gastrointestinal tumors located on the anterior wall of the rectum and protruding into the vagina. The use of Martius flap interposition is convenient and can be employed to prevent rectovaginal fistula.
PubMed: 38946097
DOI: 10.3393/ac.2023.00556.0079 -
The Journal of Reproduction and... Jun 2024Retained placenta (RP) adversely affects postpartum productivity and reproduction in dairy cattle. Thus, methods to predict the occurrence of RP before calving would be...
Retained placenta (RP) adversely affects postpartum productivity and reproduction in dairy cattle. Thus, methods to predict the occurrence of RP before calving would be desirable. Herein, we assessed whether vaginal temperature measurements (which have already been applied to detect calving) could be used to predict the occurrence of RP in cattle. A vaginal temperature recording device was inserted into the vagina of 49 pregnant Holstein-Friesian heifers (n = 16) and cows (n = 33); this device recorded the vaginal temperature every 5 min until the device dropped out at calving. Serum was collected 10 days before the expected calving date. The time points of calving and placental expulsion were identified via video recordings. We further calculated calving duration (temperature decrease to calving) and placenta expulsion time (PE time = calving to placenta expulsion). The PE times were divided into four categories (0-4 h, 4-8 h, 8-12 h, and RP at >12 h), while subsequent analysis revealed that an extension of the PE time dependent on the shortening of the calving duration (P < 0.05). The vaginal temperature patterns also differed in a PE time-dependent manner, and cows with RP did not show any re-elevation of vaginal temperature. Serum analyses indicated an energy deficiency in RP cattle. These results suggest that RP may be detected early as a specific change in the vaginal temperature associated with reproductive hormone secretion.
PubMed: 38945853
DOI: 10.1262/jrd.2024-012 -
The Journal of Toxicological Sciences 2024To examine the effects of decreased food consumption on toxicological parameters in juvenile rats, rats on postnatal day 21 were fed 40%, 50% (only four weeks), and 60%...
To examine the effects of decreased food consumption on toxicological parameters in juvenile rats, rats on postnatal day 21 were fed 40%, 50% (only four weeks), and 60% less food, compared to that of controls for four or eight weeks, and clinical observations, measurement of body and organ weights, morphological differentiation analysis, clinical pathology, and macroscopic and microscopic examinations were conducted. The body weight decreased depending on the degree of food restriction (FR). Cleavage of the balano-preputial skinfold was delayed, and cell debris in the epididymal lumen was noted as a related finding after four-week FR. Vaginal opening was also delayed, and some histopathological findings, such as absence of corpus luteum in the ovary, mucinous degeneration in the vagina, and immature uterus, were noted after eight-week FR. Erythrocyte count increased after four-week FR, but slightly decreased in males only after eight-week FR, and decreased leukocyte and/or reticulocyte counts, accompanied by related histopathological findings were noted after four- and eight-week FR. In blood chemistry, the levels of total protein including globulin, glucose, triglyceride, and calcium decreased, and sodium and chloride increased after four- and eight-week FR. Increases in activities of aspartate transaminase and lactate dehydrogenase and total bilirubin levels were noted after four-week FR, which were attenuated after eight-week FR. The effects of FR seemed to be more remarkable after four weeks. In drug safety evaluation, findings caused by malnutrition should be considered in juvenile toxicity studies when decreased food consumption is observed.
Topics: Animals; Male; Female; Body Weight; Organ Size; Rats; Caloric Restriction; Time Factors; Food Deprivation; Rats, Sprague-Dawley; Rats, Wistar
PubMed: 38945843
DOI: 10.2131/jts.49.321 -
Journal of Minimally Invasive Gynecology Jun 2024To reinterpret the surgical anatomy of paracolpium in radical hysterectomy and to explore its implications for the surgery.
OBJECTIVE
To reinterpret the surgical anatomy of paracolpium in radical hysterectomy and to explore its implications for the surgery.
SETTING
The term "paracolpium," first defined by Fothergill in 1907, is essential in radical hysterectomy. However, several challenges remain unresolved. These include: (1) inconsistent terminology in relation to its defined attributes; (2) the lack of consensus on anatomical landmarks; (3) unclear associations with the cardinal and sacral ligaments; and (4) the critical implications and requirements of paracolpium resection in radical hysterectomy practices.
PARTICIPANTS
A patient in her 60s diagnosed with stage IB2 cervical cancer was enrolled in a clinical trial and assigned to the laparoscopic surgery group. A step-by-step, narrated video demonstration.
INTERVENTIONS
During the procedure, post-excision of the uterosacral, cardinal, and vesicovaginal ligaments, we identified a ligament-like structure situated between the middle third of the vagina and the pelvic wall. We have termed this structure the "paracolpium ligament." A detailed anatomical description was performed, outlining its crucial attachments.
PubMed: 38945252
DOI: 10.1016/j.jmig.2024.06.012