Metabolomic analysis reveals the biological characteristics of giant congenital melanocytic nevi.

Giant congenital melanocytic nevi (GCMN) is a congenital cutaneous developmental deformity tumor that usually occurs at birth or in the first few weeks after birth, but its pathogenesis is still unclear. In this study, nuclear magnetic resonance-based metabolomics strategy was employed to evaluate the metabolic variations in serum and urine of the GCMN patients in order to understand its underlying biochemical mechanism and provide a potential intervention idea. Twenty-nine metabolites were observed to change significantly in serum and urine metabolomes, which are mainly involved in a variety of metabolic pathways including glyoxylate and dicarboxylate metabolism, TCA cycle and metabolisms of amino acids. The substantial cores of all the disturbed metabolic pathways are related to amino acid metabolism and carbohydrate metabolism and regulate the physiological state of the GCMN patients. Our results provide the physiological basis and physiological responses of GCMN and will be helpful for better understanding the molecular mechanisms of GCMN in future research.

Comparison of clinical effectiveness and subsequent fertility between hysteroscopic resection and vaginal repair in patients with cesarean scar defect: a prospective observational study.

OBJECTIVE: To evaluate the clinical effectiveness and pregnancy rate after hysteroscopic resection (HR) and/or vaginal repair (VR) in patients with cesarean scar defect (CSD). METHODS: This prospective observational study enrolled 191 patients who received CSD surgery in the First affiliated hospital of Sun Yat-sen University between September 2019 to February 2022 (96 in HR and 95 in VR, respectively). Patient follow-up were performed three months after surgery in both groups by transvaginal ultrasound to confirm the presence of fluid in the niche, along with the resolution of prolonged menses at the same time. The primary outcome was the clinical effectiveness between HR and VR, identified by the resolution of prolonged menses. RESULTS: The rates of niche-fluid disappearance (70.1% vs 60.2%, P = 0.176) and prolonged menses resolution (74.8% vs 80.0%, P = 0.341) were comparable for HR and VR. A subgroup analysis for niche size revealed that HR provides patients with small niche a more favorable rate of menstrual resolution compared to VR (size of niche ≤ 15 mm2, aOR = 3.423, 95% confidence interval [CI] 1.073-10.918), but patients with large niche experience a lower rate of resolution compared to VR (size of niche > 25 mm2, aOR = 0.286, 95% CI 0.087- 0.938). During follow-up, 41 patients who wanted to conceive became pregnant. Kaplan-Meier estimates of the cumulative probability of pregnancy at 12 months and 24 months were 47.1% (95% CI: 34.5%, 58.8%) and 63.8% (95% CI: 52.5%, 72.9%), respectively. The median pregnancy time was 22 months (95% CI: 14.2, 29.8) after VR and 12 months (95% CI: 8.3, 15.7, Gehan-Breslow-Wilcoxon P = 0.021) after HR. Among patients with subsequent infertility, 31.6% achieved pregnancy by unassisted mode and 29.8% by IVF/ICSI. Moreover, among patients with previously failed IVF/ICSI treatment, 60% (12/20) obtained pregnancy, including 71.4% (10/14) after HR and 33.3% (2/6) after VR. CONCLUSIONS: Hysteroscopic resection is as effective as vaginal repair at relieving symptoms of CSD-associated prolonged menses. Hysteroscopic resection is the modality of choice with an improvement in prolonged menses for small niche, while vaginal might be considered for a large niche. Furthermore, surgical intervention could improve the clinical pregnancy rate of CSD patients. All of these provide evidence for the individualized management of CSD.

Chronic endometritis incidence in infertile women with and without polycystic ovary syndrome: a propensity score matched study.

BACKGROUND: Polycystic ovary syndrome (PCOS) is known to be associated with chronic low-grade inflammation and endometrial dysfunction. Chronic endometritis (CE) is a type of local inflammation that can contribute to endometrial dysfunction in infertile women. Some clinicians recommend screening for CE in women at high risk, such as those with endometrial polyps. However, it is still uncertain whether there is a relationship between PCOS and CE, as well as whether women with PCOS require enhanced screening for CE. This study was to assess the incidence of CE among infertile women with PCOS by hysteroscopy combined with histopathology CD138 immunohistochemical staining of endometrium. METHODS: A total of 205 patients in the PCOS group and 4021 patients in the non-PCOS group from July 2017 to August 2022 were included in this retrospective study. After nearest-neighbor 1:4 propensity score matching (PSM), 189 PCOS patients were matched with 697 non-PCOS patients. Basic information was recorded. The CE incidence was compared. The risk factors affecting CE incidence were also analyzed. RESULTS: No significantly higher CE incidence in infertile women with PCOS were found either in total analysis or after PSM (P = 0.969; P = 0.697; respectively). Similar results were discovered in the subgroup of Body Mass Index (BMI) (P = 0.301; P = 0.671; P = 0.427; respectively) as well as the four PCOS phenotypes (P = 0.157). Intriguingly, the incidence of CE increased as BMI increased in the PCOS group, even though no significant differences were found (P = 0.263). Multivariate logistic regression showed that age, infertility duration, infertility type, PCOS, and obesity were not the independent risk factors affecting CE incidence. CONCLUSION: The incidence of CE in PCOS patients did not significantly increase compared to non-PCOS patients. Similarly, no significant differences in the incidence of CE were observed among different PCOS phenotypes. The current evidence does not substantiate the need for widespread CE screening among PCOS women, potentially mitigating the undue financial and emotional strain associated with such screenings.

Discover boy specific-biomarkers and reveal gender-related metabolic differences in central precocious puberty.

The incidence of central precocious puberty (CPP) in boys is rising, but lack of effective molecular biomarkers often leads to delayed treatment and thus the terrible clinical complications in adulthood. This study aims to identify the specific-biomarkers of CPP boys and understand the gender-related differences in metabolic characteristics of CPP. The specific-biomarkers of CPP boys were identified from serum by cross-metabolomics combined with linear discriminant analysis effect size analysis after age correction, and union receiver operating characteristic curve analyses were perform to optimize the combination of specific-biomarkers. The differences in metabolic characteristics between boys and girls with CPP were explored by cross-metabolomics and weighted gene co-expression network analysis. Results show that CPP activated in advance the HPG axis and induced gender-related clinical phenotypes. Seven serum metabolites were identified as specific-biomarkers of CPP boys, including acetoacetate, aspartate, choline, creatinine, myo-inositol, N,N-dimethylglycine and N-Acetyl-glycoprotein. The combination of aspartate, choline, myo-inositol and creatinine achieved an optimized diagnosis, where AUC is 0.949, prediction accuracy for CPP boys is 91.1%, and the average accuracy is 0.865. The metabolic disorders of CPP boys mainly involve in glycerophospholipid metabolism, and synthesis and degradation of ketone bodies. Betaine, glutamine, isoleucine, lactate, leucine, lysine, pyruvate, α-&ß-glucose were identified as gender-related biomarkers for CPP, and they are mainly involved in glycolysis/gluconeogenesis, pyruvate metabolism, and alanine, aspartate and glutamate metabolism. Biomarkers combination provides a promising diagnostic potential for CPP boy with a favorite sensitivity and specificity. In addition, the differences of metabolic characteristics between boys and girls with CPP will contribute to the development of individualized clinical treatments in CPP.

How platelet-rich plasma (PRP) intra-uterine injection improve endometrial receptivity of intrauterine adhesions in women: A time-series-based self-controlled study.

Platelet-rich plasma (PRP) treatment proven to improve fertility outcomes in patients with a poor endometrial environment. However, the mechanism is not yet clear. In this study, we recruited 6 patients with infertility due to IUA and 6 normal control women. The subjects in the IUA group collected samples before and after PRP treatment. Endometrial receptivity was improved after PRP treatment. After PRP treatment, the endometrial NK cells, CD8 T cells and Th1 cells were significantly lower than those before treatment. Functional enrichment analysis suggested that the effects of changes in microbial composition played an important role in changes in the endometrial immune environment. Among them, the most significant difference was Bacillus. Our self-controlled cohort in this study can fully describe the detailed mechanism by which PRP treatment improves the endometrial environment.

Suppressive Effects of Ursolic Acid on Human Endometriotic Stromal Cells Survival.

BACKGROUND/AIMS: The identification of new compound candidates for endometriosis treatment is needed. Cyclooxygenase-2 (COX-2) is considered a crucial target to control the progress and recurrence of endometriosis. Here, we identified ursolic acid (UA) as a natural inhibitor of COX-2 and investigated its effects on endometriosis progression. METHODS: Primary human endometriotic stromal cells isolated from patients with endometriosis were exposed to UA at concentrations of 15, 30, 45, and 60 µM. 3-(4,5-Dimethylthiaziazol-2-yl)-2,5-diphenyl tetrazolium bromide assays, 5'-bromo-2'-deoxy-uridine assays, and Caspase-3 activity measurements were performed to detect cell growth and apoptosis. Enzyme-linked immunosorbent assays were used to detect COX-2 and vascular endothelial growth factor (VEGF) protein expression and prostaglandin E2 (PGE2) levels. Capillary-tubule formation assays using human umbilical vein endothelial cells were also carried out to determine angiogenesis. RESULTS: UA significantly decreased cell viability, inhibited proliferation, and increased caspase-3 activity in a dose-dependent manner. COX-2 protein expression and the subsequent PGE2 production were both reduced by UA. Meanwhile, UA exposure decreased VEGF secretion in the stromal cells and the capillary-tubule formation assay confirmed the inhibitory effect of UA on angiogenesis. Furthermore, UA increased the phosphorylation of c-Jun N-terminal kinase and p38. CONCLUSIONS: Our data suggest that UA plays a role as a natural inhibitor of COX-2 to control the survival of human endometriotic stromal cells by inhibiting proliferation and angiogenesis and promoting apoptosis.

Autologous platelet-rich plasma infusion improves clinical pregnancy rate in frozen embryo transfer cycles for women with thin endometrium.

BACKGROUND: Adequate thickness of the endometrium has been well recognized as a critical factor for embryo implantation. This was a prospective cohort study to investigate the benefits of platelet-rich plasma (PRP) for women with thin endometrium who received frozen embryo transfer (FET) program in a larger number of patients and explore the underlying mechanism. METHODS: In this study, we investigated the effects of PRP in women with thin endometrium in FET program. 64 patients with thin endometrium (<7 mm) were recruited. PRP intrauterine infusion was given in PRP group during hormone replacement therapy (HRT) cycle in FET cycles. RESULTS: After PRP infusion, the endometrium thickness in PRP group was 7.65 ±â€Š0.22 mm, which was significantly thicker than that in control group (6.52 ±â€Š0.31 mm) (P <.05). Furthermore, PRP group had lower cycle cancellation rate when compared to control group (19.05% vs. 41.18%, P <.01). The implantation rate and clinical pregnancy rate in PRP group were significantly higher than those in control group (27.94% vs 11.67%, P <.05; 44.12% vs 20%, P <.05, respectively). PRP blood contained 4 folds higher platelets and significantly greater amounts of growth factors including platelet-derived growth factor (PDGF)-AB, PDGF-BB, and transforming growth factor (TGF)-ß than peripheral blood (P <.01). CONCLUSIONS: PRP plays a positive role in promoting endometrium proliferation, improving embryo implantation rate and clinical pregnancy rate for women with thin endometrium in FET cycles.

The impact of endometrioma and laparoscopic cystectomy on ovarian reserve and the exploration of related factors assessed by serum anti-Mullerian hormone: a prospective cohort study.

BACKGROUND: To evaluate the impact of the presence of endometrioma and laparoscopic cystectomy on ovarian reserve as assessed by serum anti-Müllerian hormone (AMH) level. In addition, factors related to the decline in ovarian reserve were analyzed. METHODS: From June 2013 to January 2014, we prospectively included 40 women with endometriomas as the study group (group A), 36 women with tubal factor infertilities as control group 1 (group B) and 22 women with the other benign ovarian cysts as control group 2 (group C). The women with ovarian cysts underwent laparoscopic cystectomy. Serum AMH levels were determined preoperatively and at 1 month after surgery. RESULTS: The endometrioma group had lower AMH levels (1.53 ± 1.37 ng/ml) compared with the other benign ovarian cyst group (2.20 ± 1.23 ng/ml) and the tubal factor infertility group (2.82 ± 1.74 ng/ml). The rate of serum AMH decline 1 month after surgery in the endometrioma group (0.62 ± 0.35) was larger than the decline in the other benign ovarian cyst group (0.32 ± 0.30). The preoperative AMH level showed a significant correlation with patient age (group A, r = -0.32; group B, r = -0.54; group C, r = -0.71); there was a statistically significant correlation between the rate of serum AMH decline and endometrioma diameter as well as with the preoperative serum AMH level. In addition, the rate of serum AMH decline was larger for bilateral endometriomas than for unilateral endometriomas, but there was no similar correlation in the other benign ovarian cyst group. The rate of AMH decline after surgery in the subgroup of >7 cm was significantly higher than in the subgroup of ≤7 cm. CONCLUSIONS: Ovarian endometriomas per se may damage ovarian reserve, and cystectomy of endometriomas may cause greater damage to ovarian reserve compared with other benign ovarian cysts. The operation-related damage to the ovarian reserve was positively related to whether the endometriomas were bilateral, as well as cyst size (especially for cysts >7 cm), but was negatively related to the preoperative serum AMH level. Age was a negative factor that affected the ovarian reserve.

Transvaginal management of cesarean scar section diverticulum: a novel surgical treatment.

BACKGROUND: The aim of this study was to investigate the clinical value of transvaginal management of cesarean section scar diverticulum. MATERIAL/METHODS We evaluated 64 patients receiving transvaginal management of previous cesarean scar defect (PCSD). RESULTS: The PCSD was successfully treated by transvaginal surgery, without evident complications. The mean operation time was 33.6±4.1 min, blood loss was 37.9±16.8 ml, and the mean hospital stay after surgery was 6±2.9 days. Symptoms related to the prolonged menstruation in 53 patients were improved after surgery, vaginal bleeding time was reduced by an average of 7.3±2.8 days, and a significant difference was noted between the mean pre- and post-operative duration of menstruation (P<0.01). Of 11 patients with guttate between menstrual periods, guttate was absent in 9 patients and improved in 2. Clinical improvement was observed in 85.9% (55/64). CONCLUSIONS: Transvaginal intervention is feasible and safe for the management of PCSD.

Role of angiogenesis in endometrial repair of patients with severe intrauterine adhesion.

OBJECTIVE: To detect vascular endothelial growth factor (VEGF) expression and micro-vessel density (MVD) in patients with severe intrauterine adhesion before and after therapy, and to preliminarily explore the role of angiogenesis in the therapy of severe intrauterine adhesion. METHODS: A total of 36 patients with severe intrauterine adhesion were prospectively recruited into the treatment group. In the control group, 20 patients with normal uterine were recruited. Patients with severe intrauterine adhesion received transcervical resection of adhesions under hysteroscope and then received artificial hormone therapy for 3 months. METHODS: The changes in the organelles of endometrial cells were evaluated under an electric microscope; Immunohistochemistry was done to detect the VEGF expression and MVD in patients with severe intrauterine adhesion, which was compared with that in the control group; VEGF expression and MVD were compared among patients with different prognoses. RESULTS: Electric microscopy showed vascular closure and hypoxic changes in the endometrial tissues of patients with intrauterine adhesion. After treatment, angiogenesis was observed, and the hypoxic changes in the endometrial glands and interstitium were also improved. Moreover, the VEGF expression and score of MVD also increased significantly when compared with those before treatment and in the control group. The VEGF expression and MVD score in intrauterine adhesion patients recovering from treatment were significantly higher than those in patients non-responding to treatment. CONCLUSION: In patients with intrauterine adhesion, the endometrial tissues present with vascular closure, and angiogenesis will be present in the endometrial tissues after treatment. The angiogenesis in the endometrial tissues may affect the endometrial repair.