Mixed-lineage leukaemia 1 contributes to endometrial stromal cells progesterone responsiveness during decidualization.

Studies have reported that non-receptive endometrium or abnormal decidualization was closely related to recurrent implantation failure (RIF). MLL1 is a histone H3 lysine 4 trimethylation (H3K4me3) transferase that regulates the transcriptional activation of target genes. The role of MLL1 has been underexplored during decidualization. In our research, we found the expression of MLL1 was closely related to endometrial receptivity, and it was responsible to hormone stimulation. Inhibiting the function of MLL1 by MM102 reduced the transformation of HESCs. Furthermore, down-regulation of MLL1 by siRNA transfection significantly decreased PGR and its target genes expression. MLL1 act as a co-activator of ERα, and both of them were recruited to PGR regulatory regions, thus promote PGR transcription. Our study showed that MLL1 plays a key role in promoting progesterone signalling transmission.

The risk of endometriosis after exposure to endocrine-disrupting chemicals: a meta-analysis of 30 epidemiology studies.

Endocrine-disrupting chemicals (EDCs) are suspected to be associated with endometriosis (EMs). This study aimed to synthesize published data and evaluate the relationship between four classic EDCs exposure and the risk of EMs. A systematic literature search for original peer reviewed papers was performed in the databases PubMed, EMBASE, and Web of Science based on inclusion criteria up to January 2018. Subsequently, a total of 20 papers conducting 30 studies fulfilled the eligibility criteria and were included in this meta-analysis (four studies for bisphenol A (BPA), 12 studies for polychlorinated biphenyls (PCBs), eight studies for organochlorine pesticides (OCPs), and six studies for phthalate esters (PAEs)). The overall odds ratio (OR) across all exposures and EMs was 1.41 (95% confidence interval (CI): 1.23-1.60). When assessing four specific chemicals, respectively, consistent increases in the risk of EMs were found in PCBs group (OR = 1.58; 95% CI: 1.18-2.12), OCPs group (OR = 1.40; 95% CI: 1.02-1.92) and PAEs group (OR = 1.27; 95% CI: 1.00-1.60), while BPA showed no significant association with EMs. Besides, in the di-(2-ethylhexyl)-phthalate (DEHP) group - the most commonly used PAEs, significant risk was also found (OR = 1.42; 95% CI: 1.19-1.70). The current meta-analysis strengthens the evidence that specific EDCs or their metabolites may promote the occurrence of EMs.

The efficacy and safety of bevacizumab combined with chemotherapy in treatment of HER2-negative metastatic breast cancer: a meta-analysis based on published phase III trials.

Bevacizumab (Bev) combined with chemotherapy significantly improves progression-free survival (PFS) but not overall survival (OS) in patients with human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC). The efficacy and safety depend on the type of chemotherapy combined with Bev. We performed a meta-analysis of phase III trials to evaluate the efficacy and safety of Bev + standard chemotherapy for HER2-negative MBC. The Cochrane Central Register of Controlled Trials, the Cochrane databases, EMBASE, MEDLINE, and ClinicalTrials.gov were analyzed. The primary outcomes included PFS, OS, and toxicity. Event-based hazard ratios (HRs) and relative risks (RRs) were expressed with the 95% confidence intervals (CIs). Four randomized controlled trials consisting of 3082 patients were included. Bev + standard chemotherapy improved PFS (HR 0.70, CI 0.64-0.77, P = 0.000) but had no effect on OS (HR 0.92, CI 0.82-1.02, P = 0.119). Bev + chemotherapy increased the incidence of febrile neutropenia (RR 1.45, CI 1.00 to 2.09, P = 0.048), proteinuria (RR 11.68, CI 3.72-36.70, P = 0.000), sensory neuropathy (RR 1.33, CI 1.05-1.70, P = 0.020), and grade ≥3 hypertension (RR 13.94, CI 7.06-27.55, P = 0.000). No differences in efficacy were observed between Bev + paclitaxel and Bev + capecitabine (Cape), but Bev + Cape increased the incidence of neutropenia. Bev + standard chemotherapy improved PFS in HER2-negative MBC patients. No benefit in OS was observed. Bev + Cape and Bev + paclitaxel had similar treatment efficacy, but Bev + Cape had a higher incidence of neutropenia.

A herbal composition of semen hoveniae, radix puerariae, and fructus schisandrae shows potent protective effects on acute alcoholic intoxication in rodent models.

This study is designed to evaluate the effects of a herbal composition of Semen Hoveniae, Radix Puerariae and Fructus Schisandrae (SRF) against acute alcoholic intoxication. The animals were treated with SRF extract (SRFE) for 14 days, and ethanol was conducted subsequent to the final treatment. The effects of SRFE on righting reflex, inebriety rates, kinetic parameters of blood ethanol and acetaldehyde were determined. In addition; levels of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), the activities of cytochrome P450 2E1 (CYP2E1), selected antioxidative enzymes, and the contents of malonaldehyde (MDA) were measured. SRFE-pretreated rodents exhibited lower rates of intoxication, longer times to loss of righting reflex, and shortened times to recovery of righting reflex than in controls. The peak concentrations and area under the time-concentration curves were lower in the pretreated animals than in controls, which corresponded to higher levels of ADH and ALDH in both gastrointestines and livers of the SRFE-treated animals. The activities of CYP2E1 were lower in SRFE-pretreated animals, which also exhibited higher activities of some antioxidant enzymes and lower hepatic MDA levels. These findings suggest that the anti-inebriation effects of SRFE may involve inhibition of ethanol absorption, promotion of ethanol metabolism, and enhancing hepatic anti-oxidative functions.

Association of low birthweight and small for gestational age with maternal ferritin levels: A retrospective cohort study in China.

Background: Birthweight have profound impacts on health status throughout lifetime, however, the relationship between maternal ferritin level in pregnancy and birthweight of the newborn remains controversial. Objective: This retrospective cohort research was to analyze the association between maternal ferritin levels during pregnancy with birthweight outcomes, primarily for low birthweight (LBW) and small for gestational age (SGA). Methods: Newborns weighing lower than 2,500 grams were defined as LBW. SGA is defined as birthweight lower than the 10th percentile of the distribution of newborns' birthweight of the same gestational age. Multivariable logistic regressions have been used to explore the association of maternal ferritin levels and birthweight related outcomes, in which the ferritin concentration was logarithm transformed in the model. We further used restricted cubic spline models to explore linear/non-linear dose-response manners of ferritin level and birthweight outcomes. Results: A total of 3,566 pregnant women were included in the study. In the results of the present study, we observed that maternal ferritin levels were linearly associated with the risk of LBW (p-trend = 0.005) and SGA (p-trend = 0.04), with the adjusted odds ratios (ORs) of 1.78 (95% CI 1.37-2.32) for LBW and 1.87 (95% CI 1.38-2.54) for SGA with an increase in Ln-ferritin concentrations per unit. The adjusted ORs across quartiles of ferritin levels were 2.14 (95% CI 1.03-4.47) for Quartile 2, 3.13 (95% CI 1.47-6.69) for Quartile 3, and 3.63 (95% CI 1.52-8.68) for Quartile 4 for LBW. The adjusted ORs of LBW and SGA among women using supplemental iron were 0.56 (95% CI 0.38, 0.85) and 0.65 (95% CI 0.40, 1.05) compared with non-users, respectively. Conclusions: Our findings found a linear dose-response relationship between ferritin levels and an increased risk of poor birthweight outcomes, suggesting that maternal ferritin level during pregnancy may provide an additional predictor for differentiating poor birthweight related outcomes. Further exploration should be conducted to ensure maternal ferritin thresholds and iron supplement doses.

Recurrent radiation-associated leiomyosarcoma after postoperative radiotherapy for breast invasive ductal carcinoma: a case report and literature review.

Radiation-associated leiomyosarcoma has a poor prognosis. Fewer than 20 cases of radiation-associated leiomyosarcoma of the breast have been reported in the literature to date. We report the first case of recurrent radiation-associated leiomyosarcoma after invasive ductal carcinoma postoperative radiotherapy. A 45-year-old female patient with no familial history of cancer underwent breast-conserving surgery (BCS) and dissection of axillary lymph nodes for invasive ductal carcinoma in the right upper outer region in 2014. After the operation, she received adjuvant chemotherapy followed by radiotherapy and endocrine therapy. She came to our institution for a lump in the right breast radiation region in 2019. Ultrasonography revealed an oval mass, with ill-defined borders, irregular margins, and speculation at 6 o'clock direction of the right breast, approximately 2.5 cm from the nipple. Ultimately, excisional biopsy established the pathological diagnosis of leiomyosarcoma. The female then underwent simple mastectomy of the right breast. The patient received no radiation or chemotherapy after the simple mastectomy. After 13 months of follow-up, a lump was found in the right chest wall and axillary levels of the radiation region. Excisional biopsy confirmed the pathological diagnosis of leiomyosarcoma. This rare case indicated that simple mastectomy seemed to be inadequate treatment for radiation-associated leiomyosarcoma.

Micro-RNA miR-542-3p suppresses decidualization by targeting ILK pathways in human endometrial stromal cells.

Decidualization of human endometrial stromal cells (HESCs) is a vital step for successful pregnancy. However, the process by which micro-RNAs (miRNAs) regulate decidualization remains elusive. Our current study was designed to identify the mechanism of miRNA miR-542-3p and its potential targets in regulating decidualization. The results showed that miR-542-3p was down-regulated in HESCs. Luciferase assay confirmed that integrin-linked kinase (ILK) is a direct target of miR-542-3p. Overexpression of miR-542-3p resulted in decreased ILK and downstream transforming growth factor ß1 (TGF-ß1) and SMAD family member 2 (SMAD2) expression. Additional expression of ILK attenuates the miR542-3p-induced down-regulation of TGF-ß1 and SMAD2, changes properties such as suppression of proliferation and invasion, and induction of apoptosis, thereby affecting the differentiation of HESCs. Moreover, miR-542-3p overexpression caused down-regulation of the angiogenic factors vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2) and matrix metalloproteinase-9 (MMP-9), and the supernatant of HESCs overexpressing miR-542-3p inhibited the formation of tubular structures in human umbilical vein endothelial cells (HUVECs), suggesting that miR-542-3p inhibits angiogenesis of HUVECs. Furthermore, in our mouse model, following injection of miR-542-3p mimic into the endometrium of mice at pregnancy day 8 (D8), we found decreased miR-542-3p expression and loss of embryo implantation sites. In conclusion, miR-542-3p can affect the process of endometrial decidualization by down-regulating ILK. The present study adds further understanding of the process and regulation of decidualization.

Midwifery and Nursing Strategies to protect against COVID-19 During the Third Trimester of Pregnancy.

OBJECTIVE: The rapid pace of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic (COVID-19) presents significant challenges to midwives and nurses. This study aimed to explore midwifery and nursing interventions to limit the transmission of COVID-19 among women in their third trimester of pregnancy, to reduce the incidence of nosocomial infection and promote safety of care for women and their infants. METHOD: We completed a retrospective review of medical records from 35 women in their third trimester of pregnancy with SARS-CoV-2, admitted to one hospital in Wuhan, China in January and February 2020. We investigated the clinical characteristics of the COVID-19 infection in pregnancy, and the individualized midwifery and nursing care offered, including environmental protection, prevention of nosocomial infection, maternal observations, monitoring of signs and symptoms of COVID-19, and psychological care. RESULT: Thirty-one women had a caesarean section, and four had vaginal births. Retrospective analysis of midwifery and nursing strategies implemented to care for these women showed no maternal complications or nosocomial infections. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: The care strategies we implemented could prevent complications and nosocomial infection in the third trimester of pregnancy, thus ensuring the safety of women and their infants. Further research needs to determine treatment priorities for women infected with COVID-19 during pregnancy and the postnatal period.

Effect of 2,3',4,4',5-Pentachlorobiphenyl Exposure on Endometrial Receptivity and the Methylation of HOXA10.

Polychlorinated biphenyls (PCBs) are one of the most common endocrine-disrupting chemicals and have obvious toxicity on human reproductive development. The aim of our study was to investigate the toxicity of chronic 2,3',4,4',5-pentachlorobiphenyl (PCB 118) exposure on embryo implantation and endometrial receptivity, with the possible mechanism of DNA methylation involved. Virgin CD-1 female mice (3 weeks old) were housed and orally treated with PCB 118 (0, 1, 10, 100 µg/kg) for a month. After mating with fertile males, the pregnant mice were killed on gestation day 4.5. Compared with the control group, implantation failures were observed in 1 µg/kg PCB 118- and 100 µg/kg PCB 118-treated groups. Abnormal endometrial morphology with open uterine lumens and densely compact stromal cells and poorly developed pinopodes were substantially in response to PCB 118 doses above, as well as the significant downregulation of implantation-associated genes (estrogen receptor 1, homeobox A10 [HOXA10], integrin subunit beta 3) and hypermethylation in the promoter region of HOXA10 further. It was confirmed that chronic exposure to PCB 118 produced an increased number of implantation failures in association with a defective uterine morphology during the implantation period. Alterations in methylation of HOXA10 could explain, at least in part, the mechanism of effects of PCB 118 exposure on the implantation process.

The correlation between exposure to BPA and the decrease of the ovarian reserve.

OBJECTIVE: This study aimed to evaluate whether exposure to bisphenol A (BPA) affects the ovarian reserve. METHODS: Follicular fluid (FF) was collected from diminished ovarian reserve (DOR) and non-DOR patients who underwent in vitro fertilization or intracytoplasmic sperm injection. ELISA was used to detect the BPA and hormones levels in 54 cases of DOR and 67 cases of non-DOR. A total of 64, five-week-old SPF C57BL/6 mice were randomly divided into four groups, of which three were exposed to 5, 50, and 500 µg/kg/day of BPA solution, and one was exposed to con oil only as the control. The weight and estrus of each mouse were recorded daily, and the E2 hormone and anti-Müllerian hormone (AMH) in the serum were detected by ELISA. The expression levels of AMH mRNA and protein were also detected. RESULTS: The BPA levels in the FF of DOR patients were significantly higher than those of non-DOR patients (234.048±81.736 ng/L vs. 193.300±67.225 ng/L, P<0.01); The AMH and E2 levels in the FF of DOR patients were lower than those of non-DOR patients ([555.689+74.224] pg/ml vs. [587.178+77.731] pg/ml, P<0.05, [209.720+31.556] pg/ml vs. [221.845+32.632] pg/ml, P<0.05). The BPA concentration was correlated with the AMH and E2 levels in the FF (rBPA & AMH=-0.312, P<0.05; rBPA & E2=-0.290, P<0.05); in the animal experiment, the levels of serum AMH and E2 as well as the expression levels of the AMH gene and protein in the BPA treatment group displayed downward trends. The concentrations of the 5 and 500 µg/kg/day groups decreased significantly (P<0.05). CONCLUSION: The increased BPA in the FF may promote the pathogenesis of DOR. BPA did not present a single-dose effect on the mouse ovary. Sub-chronic exposure to a low dose of BPA can reduce the ovarian reserve in female mice.

GnRH analogues may increase endometrial Hoxa10 promoter methylation and affect endometrial receptivity.

The present study aimed to investigate whether gonadotropin-releasing hormone analogues (GnRH-as), including GnRH agonists and antagonists, affect endometrial homeobox (Hox) a10 DNA methylation during the implantation window in mice. GnRH analogue mouse models were used and were treated with either human menopausal gonadotropin (HMG) and a GnRH agonist or HMG and a GnRH antagonist. Uterus samples were collected 48 h after GnRH analogue treatment or ovulation. Bisulfite sequencing polymerase chain reaction (PCR), quantitative-PCR and western blot analysis were performed to assess Hoxa10 and integrin ß3 expression. Scanning electron microscope analyses were conducted to analyze pinopode development. Compared with the natural cycle control mice, mice in the GnRH analogue groups were found to exhibit increased levels of methylation at the Hoxa10 promoter, decreased Hoxa10 mRNA and protein expression and disrupted pinopode development. These findings suggest that GnRH-as may be associated with altered Hoxa10 DNA methylation, thus GnRH-as may affect uterine Hoxa10 expression and endometrial receptivity.

Effect of Bisphenol A on invasion ability of human trophoblastic cell line BeWo.

Bisphenol A (BPA) is a kind of environmental endocrine disruptors (EEDs) that interfere embryo implantation. Trophoblast invasion plays a crucial role during embryo implantation. In this study, the effects of BPA on invasion ability of human trophoblastic cell line BeWo and its possible mechanism were investigated. BeWo cells were exposed to BPA and co-cultured with human endometrial cells to mimic embryo implantation in transwell model. The proliferation and invasion capability of BeWo cells were detected. The expression of E-cadherin, DNMT1, MMP-2, MMP-9, TIMP-1 and TIMP-2 were also analyzed. The results showed that the invasion capability of BeWo was reduced after daily exposure to BPA. BPA had biphasic effect on E-cadherin expression level in BeWo cells and expression level of DNMT1 was decreased when treated with BPA. Moreover, BPA treatment also changed the balance of MMPs/TIMPs in BeWo cells by down-regulating MMP-2, MMP-9 and up-regulating TIMP-1, TIMP-2 with increasing BPA concentration. Taken together, these results showed that BPA treatment could reduce the invasion ability of BeWo cells and alter the expression level of E-cadherin, DNMT1, TIMP-1, TIMP-2, MMP-2, and MMP-9. Our study would help us to understand the possible mechanism of BPA effect on invasion ability of human trophoblastic cell line BeWo.

Phytoestrogen intake and risk of ovarian cancer: a meta- analysis of 10 observational studies.

BACKGROUND: Epidemiology studies have shown an inconclusive relationship between phytoestrogen intake and ovarian cancer risk and there have been no relevant meta-analyses directly regarding this topic. The purpose of the present meta-analysis was therefore to investigate any association between phytoestrogen intake and ovarian cancer in detail. MATERIALS AND METHODS: We conducted a search of PubMed, EMBASE, EBSCO, the Cochrane Library, CNKI and Chinese Biomedical Database (up to April 2014) using common keywords for studies that focused on phytoestrogen and ovarian cancer risk. Study-specific risk estimates (RRs) were pooled using fixed effect or random-effect models. RESULTS: Ten epidemiologic studies were finally included in the meta-analysis. The total results indicated higher phytoestrogen intake was associated with a reduced ovarian cancer risk (RR, 0.70; 95%CI: 0.56-0.87). The association was similar in sensitivity analysis. Meta regression analysis demonstrated sources and possibly types and regions as heterogeneous factors. Subgroup analysis of types, sources and regions showed that isoflavones (RR: 0.63; 95%CI: 0.46, 0.86), soy foods (RR: 0.51; 95%CI: 0.39, 0.68) and an Asian diet (RR: 0.48; 95%CI: 0.37, 0.63) intake could reduce the incidence of ovarian cancer. CONCLUSIONS: Our findings show possible protection by phytoestrogens against ovarian cancer. We emphasize specific phytoestrogens from soy foods, but not all could reduce the risk. The habit of plentiful phytoestrogen intake by Asians is worthy to recommendation. However, we still need additional larger well designed observational studies to fully characterize underlying associations.