Exploring myometrial microenvironment changes at the single-cell level from nonpregnant to term pregnant states.

The microenvironment and cell populations within the myometrium play crucial roles in maintaining uterine structural integrity and protecting the fetus during pregnancy. However, the specific changes occurring at the single-cell level in the human myometrium between nonpregnant (NP) and term pregnant (TP) states remain unexplored. In this study, we used single-cell RNA sequencing (scRNA-Seq) and spatial transcriptomics (ST) to construct a transcriptomic atlas of individual cells in the myometrium of NP and TP women. Integrated analysis of scRNA-Seq and ST data revealed spatially distinct transcriptional characteristics and examined cell-to-cell communication patterns based on ligand-receptor interactions. We identified and categorized 87,845 high-quality individual cells into 12 populations from scRNA-Seq data of 12 human myometrium tissues. Our findings demonstrated alterations in the proportions of five subpopulations of smooth muscle cells in TP. Moreover, an increase in monocytic cells, particularly M2 macrophages, was observed in TP myometrium samples, suggesting their involvement in the anti-inflammatory response. This study provides unprecedented single-cell resolution of the NP and TP myometrium, offering new insights into myometrial remodeling during pregnancy.NEW & NOTEWORTHY Using single-cell RNA sequencing and spatial transcriptomics, the myometrium was examined at the single-cell level during pregnancy. We identified spatially distinct cell populations and observed alterations in smooth muscle cells and increased M2 macrophages in term pregnant women. These findings offer unprecedented insights into myometrial remodeling and the anti-inflammatory response during pregnancy. The study advances our understanding of pregnancy-related myometrial changes.

Serpin family E member 1 enhances myometrium contractility by increasing ATP production during labor.

The uterine contraction during labor, a process with repetitive hypoxia and high energy consumption, is essential for successful delivery. However, the molecular mechanism of myometrial contraction regulation is unknown. Serpin family E member 1 (SERPINE1), one of the most upregulated genes in laboring myometrium in both transcriptome and proteome, was highlighted in our previous study. Here, we confirmed SERPINE1 is upregulated in myometrium during labor. Blockade of SERPINE1 using small interfering RNA (siRNA) or inhibitor (Tiplaxtinin) under hypoxic conditions in myocytes or myometrium in vitro showed a decrease contractility, which was achieved by regulating ATP production. Chromatin immunoprecipitation (ChIP-seq), Co-immunoprecipitation (Co-IP), and glutathione-S-transferase (GST) pull down explored that the promoter of SERPINE1 is directly activated by hypoxia-inducible factor-1α (HIF-1α) and SERPINE1 interacts with ATP Synthase Peripheral Stalk Subunit F6 (ATP5PF). Together they enhance hypoxia driven myometrial contraction by maintaining ATP production in the key oxidative phosphorylation pathway. The results provide new insight for uterine contraction regulation, and potential novel therapeutic targets for labor management.

Trophoblast cellular adhesion molecule expression regulated by different genes and their correlation with pregnancy-induced hypertension.

It was to study trophoblast cell (TC) adhesion molecules regulated by different genes in the placental tissue (PT) of patients with pregnancy-induced hypertension (PIH), and the correlation with the severity of PIH. 42 patients with PIH (13 cases in the mild PIH group, 11 cases in the moderate PIH group, and 18 cases in the severe PIH group) and 40 patients with normal pregnancy (NP group) were included. mRNA and protein levels in matrix metalloproteinase (MMP)-9, MMP-2, tissue inhibitor of metalloproteinases (TIMP)-1, and TIMP-2 of all patients were determined by semi-quantitative polymerase chain reaction (PCR) and Western blotting (WB), respectively. Compared to the NP group, MMP-9 and MMP-2 mRNA levels as well as their proteins in PT significantly decreased in PIH groups (P<0.05). MMP-9 mRNA was greatly lower in the severe PIH group than mild PIH group (P<0.05). MMP-2 mRNA in moderate and severe PIH groups was much lower than NP and mild PIH groups, and that in the severe PIH group was considerably lower than the moderate PIH group (P<0.05). TIMP-1 mRNA and its protein highly increased in PT in PIH groups than NP group (P<0.05). TIMP-2 mRNA was remarkably higher in the severe PIH group than in the NP group (P<0.05). mRNA and proteins of MMP-9 and MMP-2 decreased in PT of PIH patients, while TIMP-1 mRNA and its protein increased, which were correlated with the severity of PIH. MMP-9, MMP-2, and TIMP-1 were involved in the pathogenesis of PIH by regulating the infiltration of TCs.

sFlt-1/PIGF ratio positive associated with non-dipper type change in ambulatory blood pressure monitoring(ABPM) for preeclampsia development.

In order to explore relationship of ambulatory blood pressure monitoring (ABPM) and soluble fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PlGF) in suspected preeclampsia(PE), suspected PE participants in 28 + 0 to 33 + 6 weeks underwent ABPM and sFlt-1/PlGF from July 2020 to July 2022 were included(N = 476) in study. ABPM parameters were compared between sFlt-1/PlGF ≥38 and <38 groups. Correlation analysis was performed between ABPM and sFlt-1/PlGF, and logistic regression was used to explore prediction value for PE in 2 weeks. One hundred eighteen cases developed PE in 2 weeks with 114 from sFlt-1/PlGF ≥38 group. Daytime and nighttime BP were all increased,with increased non-dipper (58.4% vs. 30.3%), riser (22.1% vs. 13.1%) and and decreased Dipper (15.4% vs. 45.9%) type of ABPM in sFlt-1/PlGF ≥38 groups (P < 0.05).The riser group had the highest sFlt-1 and lowest PlGF. sFlt-1/PlGF and sFlt-1 were all positively correlated with systolic (SBP) & diastolic blood pressure(DBP)(P < 0.01), in which correlation coefficients of daytime and nighttime BP with sFlt-1 were ß = 150.05 & 157.67 for SBP, ß = 234 and 199.01 for DBP, respectively. However, PlGF was only negatively associated with nighttime SBP and DBP(P < 0.05), with no correlation with daytime BP (P > 0.05).Combining sFlt-1/PlGF and ABPM model, showed sFlt-1/PlGF (aOR = 2.01 (1.69-2.36)), Nighttime DBP (aOR = 1.14 (1.02-1.28)) contributed to preeclampsia prediction, and had improved predictive value compared to ABPM or sFlt-1/PlGF models alone(P < 0.05). sFlt-1/PlGF ratio was positively correlated with BP parameters, whereas PIGF was only negatively correlated with nocturnal BP and increased non-dipper type change in ABPM, which had a synergistic effect with sFlt-1/PlGF on PE prediction.

Intrauterine death in vasa previa without hemorrhage: case reports.

Antepartum and intrapartum hemorrhage from vasa previa (VP) is one of the main causes of intrauterine fetal death (IUFD). Here, we present two cases with type I VP in which velamentous cord insertion below the fetal head and overlying the cervix were reported by prenatal ultrasound scanning, and IUFD occoured after 35 weeks with no signs of prenatal bleeding but with engaged fetal head at presentation. We hypothesized that the IUFD may attributed to the compression of the unprotected umbilical vessels by the engaged fetal head. Thus we suggest that VP with a velamentous cord insertion should be considered for earlier termination of the pregnancy to avoid the risk of non-hemorrhagic adverse fetal outcomes.

Upregulated TIMP1 facilitates and coordinates myometrial contraction by decreasing collagens and cell adhesive capacity during human labor.

Myometrial contraction is one of the key events involved in parturition. Increasing evidence suggests the importance of the extracellular matrix (ECM) in this process, in addition to the functional role of myometrial smooth muscle cells, and our previous study identified an upregulated tissue inhibitor of metalloproteinase 1 (TIMP1) in human laboring myometrium compared to nonlabor samples. This study aimed to further explore the potential role of TIMP1 in myometrial contraction. First, we confirmed increased myometrial TIMP1 levels in labor and during labor with cervical dilation using transcriptomic and proteomic analyses, followed by real-time PCR, western blotting, and immunohistochemistry. Then, a cell contraction assay was performed to verify the decreased contractility after TIMP1 knockdown in vitro. To further understand the underlying mechanism, we used RNA-sequencing analysis to reveal the upregulated genes after TIMP1 knockdown; these genes were enriched in collagen fibril organization, cell adhesion, and ECM organization. Subsequently, a human matrix metalloproteinase (MMP) array and collagen staining were performed to determine the TIMPs, MMPs and collagens in laboring and nonlabor myometrium. A real-time cell adhesion assay was used to detect cell adhesive capacity. The results showed upregulated MMP8 and MMP9, downregulated collagens, and attenuated cell adhesive capacity in laboring myometrium, while lower MMP levels and higher collagen levels and cell adhesive capacity were observed in nonlabor. Moreover, TIMP1 knockdown led to restoration of cell adhesive capacity. Together, these results indicate that upregulated TIMP1 during labor facilitates and coordinates myometrial contraction by decreasing collagen and cell adhesive capacity, which may provide effective strategies for the regulation of myometrial contraction.

Comparison of fetal heart rate baseline estimation by the cardiotocograph network and clinicians: a multidatabase retrospective assessment study.

Background: This study aims to compare the fetal heart rate (FHR) baseline predicted by the cardiotocograph network (CTGNet) with that estimated by clinicians. Material and methods: A total of 1,267 FHR recordings acquired with different electrical fetal monitors (EFM) were collected from five datasets: 84 FHR recordings acquired with F15 EFM (Edan, Shenzhen, China) from the Guangzhou Women and Children's Medical Center, 331 FHR recordings acquired with SRF618B5 EFM (Sanrui, Guangzhou, China), 234 FHR recordings acquired with F3 EFM (Lian-Med, Guangzhou, China) from the NanFang Hospital of Southen Medical University, 552 cardiotocographys (CTG) recorded using STAN S21 and S31 (Neoventa Medical, Mölndal, Sweden) and Avalon FM40 and FM50 (Philips Healthcare, Amsterdam, The Netherlands) from the University Hospital in Brno, Czech Republic, and 66 FHR recordings acquired using Avalon FM50 fetal monitor (Philips Healthcare, Amsterdam, The Netherlands) at St Vincent de Paul Hospital (Lille, France). Each FHR baseline was estimated by clinicians and CTGNet, respectively. And agreement between CTGNet and clinicians was evaluated using the kappa statistics, intra-class correlation coefficient, and the limits of agreement. Results: The number of differences <3 beats per minute (bpm), 3-5 bpm, 5-10 bpm and ≥10 bpm, is 64.88%, 15.94%, 14.44% and 4.74%, respectively. Kappa statistics and intra-class correlation coefficient are 0.873 and 0.969, respectively. Limits of agreement are -6.81 and 7.48 (mean difference: 0.36 and standard deviation: 3.64). Conclusion: An excellent agreement was found between CTGNet and clinicians in the baseline estimation from FHR recordings with different signal loss rates.

Trophoblastic mitochondrial DNA induces endothelial dysfunction and NLRP3 inflammasome activation: Implications for preeclampsia.

AIMS: Preeclampsia (PE) is characterised by systemic vascular endothelium dysfunction. Circulating trophoblastic secretions contribute to endothelial dysfunction, resulting in PE; however, the underlying mechanisms remain unclear. Herein, we aimed to determine the potential correlation between the release of trophoblastic mitochondrial deoxyribonucleic acid (DNA) (mtDNA) and endothelium damage in PE. MATERIALS AND METHODS: Umbilical cord sera and tissues from patients with PE were investigated for inflammasome activation. Following this, trophoblastic mitochondria were isolated from HTR-8/SVneo trophoblasts under 21 % oxygen (O2) or hypoxic conditions (1 % O2 for 48 h) for subsequent treatments. Primary human umbilical veinendothelial cells (HUVECs) were isolated from the human umbilical cord and then exposed to a vehicle (phosphate-buffered saline [PBS]), mtDNA, hypo-mtDNA, or hypo-mtDNA with INF39 (nucleotide oligomerisation domain-like receptor family pyrin domain containing 3 [NLRP3]-specific inhibitor) for 12 h before flow cytometry and immunoblotting. The effects of trophoblastic mtDNA on the endothelium were further analysed in vivo using enzyme-linked immunosorbent assay (ELISA) and vascular reactivity assay. The effects of mtDNA on vascular phenotypes were also tested on NLRP3 knockout mice. RESULTS: Elevated interleukin (IL)-1ß in PE sera was accompanied by NLRP3 inflammasome activation in cord tissues. In vitro and in vivo experiments revealed that the release of trophoblastic mtDNA could damage the endothelium via NLRP3 activation, resulting in the overexpression of NLRP3, caspase-1 p20, IL-1ß p17, and gasdermin D (GSDMD); reduced endothelial nitric oxide synthase (eNOS) levels; and impaired vascular relaxation. Flow cytometric analysis confirmed that extensive cell death was induced by mtDNA, and simultaneously, a more pronounced pro-apoptotic effect was caused by hypoxia-treated trophoblastic mtDNA. The NLRP3 knockout or pharmacologic NLRP3 inhibition partially reversed tumour necrosis factor-α (TNF-α) and IL-1ß levels and endothelium-dependent vasodilation in mice. CONCLUSION: These findings demonstrate that trophoblastic mtDNA induced NLRP3/caspase-1/IL-1ß signalling activation, eNOS-related endothelial injury, and vasodilation dysfunction in PE.

Uterine electromyography (EMG) measurements to predict preterm caesarean section in patients with complete placenta previa.

The objective of the study was to evaluate uterine electrical activity (EA) with EMG methods in pregnant women with complete placenta previa with preterm caesarean section (CS). This prospective study included 78 patients with complete placenta previa who were recorded for uterine EA activity from 32 to 34 weeks of gestation. The clinical and the uterine EMG burst characteristics, that are responsible for contractions, were compared between a preterm CS group (case group, n = 33) and an elective control group (control group, n = 45). The uterine EA burst duration was longer in the case group compared with the control group (28.79 ± 3.75 vs 19.35 ± 2.56 s; p < .001). Also, the number of burst per 30 min was also higher in the case group compared with the control group (3.28 ± 0.18 vs 1.72 ± 0.22; p < .001), Similarly, the RMS was higher in the case group compared with the control group (0.07 ± 0.01 vs 0.04 ± 0.01 mV; p = .041). In addition, the PDS was higher in the case group compared with the control group (0.47 ± 0.03 vs 0.39 ± 0.02 Hz; p = .023). This study demonstrates that women with complete placenta previa have higher uterine EA at 32-34 weeks of gestation and this is associated with a higher risk of preterm CS due to massive vaginal bleeding.IMPACT STATEMENTWhat is already known on this subject? Antepartum massive bleeding in complete placenta previa causes maternal and foetal mortality and morbidity, currently there is no effective method to predict it.What do the results of this study add? This study showed in patients with complete placenta previa who were delivered preterm via emergent caesarean section, the uterine electrical activity measured by uterine electromyography (EMG) at 32-34 weeks of gestation had an active patternWhat are the implications of these findings for clinical practice and/or further research? Uterine EMG is a potential tool to measure uterine electrical activity and can guide clinical management of patients with complete placenta previa, further study are needed to confirm its effectiveness in a large sample size.

[Preliminary application of Early Start Denver Model in children with autism spectrum disorder].

OBJECTIVE: To investigate the clinical effect of the Early Start Denver Model (ESDM) in children with autism spectrum disorder (ASD). METHODS: Forty children aged 2-5 years who were diagnosed with ASD from September 2017 to January 2018 were enrolled in the study and were randomly divided into conventional intervention group and ESDM intervention group (n=20 each). Both groups were assessed by the Aberrant Behavior Checklist (ABC), Childhood Autism Rating Scale (CARS), and Clinical Global Impression-Severity (CGI-S) scale before intervention and by the ABC, CARS, CGI-S scale, and Clinical Global Impression-Improvement (CGI-I) scale after 3 months of intervention. RESULTS: After 3 months of intervention, the total scores of ABC and CARS were both significantly decreased in the two groups (P<0.01); the scores on the social withdrawal and hyperactivity subscales of ABC were significantly decreased in the conventional intervention group (P<0.01), and the scores on the mood swings, social withdrawal, hyperactivity, and stereotyped behavior subscales of ABC were significantly decreased in the ESDM intervention group (P<0.01). Compared with the conventional intervention group, the ESDM intervention group had significantly greater changes in total score of ABC, scores on three subscales of ABC (mood swings, social withdrawal, and hyperactivity), and total score of CARS after intervention (P<0.05). After 3 months of intervention, the CGI-I scoring system showed that the disease improvement was significantly better in the ESDM intervention group than in the conventional intervention group (P<0.05). CONCLUSIONS: Both conventional intervention and ESDM intervention can improve the social withdrawal and hyperactivity in children with ASD aged 2 to 5 years, but ESDM is more effective in improving the aberrant behavior of children with ASD.

Case-control study of diet in patients with cervical cancer or precancerosis in Wufeng, a high incidence region in China.

PURPOSE: To investigate the diet of patients with cervical cancer and precancerosis in the Wufeng area, a high- incidence region in China. METHODS: In the case group, 104 patients diagnosed with cervical cancer or cervical intraepithelial neoplasias (CINII/III) were recruited from the Wufeng area. Nine hundred thirty-six healthy women were selected from the same area as the matched controls. A questionnaire, which included questions about general lifestyle conditions, smoking and alcohol status, source of drinking water, green tea intake, and diet in the past year, was presented to all participants. RESULTS: Green tea intake (P=0.022, OR=0.551, 95% CI=0.330-0.919) and vegetable intake (P=0.035, OR=0.896, 95% CI=0.809-0.993) were identified as protective factors against cervical cancer or CINII/III. There was no indication of any associations of other lifestyle factors (smoking status, alcohol status, source of drinking water) or diet (intake of fruit, meat/egg/milk, soybean food, onion/garlic, staple food and pickled food) with cervical cancer. CONCLUSIONS: The results suggest that eating more fresh vegetables and drinking more green tea may help to reduce the risk of cervical cancer or CINII/III in people of the Wufeng area.

Primary screening for breast diseases among 17618 women in Wufeng area, a region with high incidence of cervical cancer in China.

In this study, the current status for breast diseases in a region with high-incidence of cervical cancer were epidemiologically investigated. From March to August, 2009, 17618 women, from Wufeng area of Hubei province, China, were recruited to screen breast diseases by using breast infrared diagnostic apparatus. Other diagnostic methods, such as B-mode ultrasound, X-ray mammography, needle biopsy and pathological examination were, if necessary, used to further confirm the diagnosis. The screening showed that 5990 of 17618 cases (34.00%) had breast diseases, 5843 (33.16%) had mammary gland hyperplasia, 48 (0.27%) had breast fibroadenoma, 11 (0.06%) had breast carcinoma, and 88 (0.50%) had other breast diseases. The peak morbidity of breast cancer was found in the women aged 50-60 ages. The morbidity of breast cancer was significantly increased in women elder than or equal to 50 years old (n=8, 0.157%) in comparison with that in the subjects younger than 50 years old (n=3, 0.024%) (u=2.327, P<0.05). It was shown that the occurrence of breast diseases was concentrated in women aged 20-40 years, while the total morbidity reached its peak at the age of 30 years and then decreased sharply after age of 40. Compared with the patients elder than or equal to 40 years old (n=3289, 27.46%), the morbidity rate of breast diseases was significantly increased in women less than 40 years old (2648 cases, 47.18%; P<0.001). However, there was no significant difference in the morbidity of breast diseases between the age group of 20-29 years and that of 30-39 years (P=0.453), and both of them were high. There was no significant association between the morbidity of breast diseases and cervical cancer. Since the morbidity of breast diseases was higher among young women, more attention should be paid to the screening of breast diseases among young women for early diagnosis.

Primary Screening for Breast Diseases among 17618 Women in Wufeng Area, a Region with High Incidence of Cervical Cancer in China / 华中科技大学学报（医学）（英德文版）

In this study,the current status for breast diseases in a region with high-incidence of cervical cancer were epidemiologically investigated.From March to August,2009,17618 women,from Wufeng area of Hubei province,China,were recruited to screen breast diseases by using breast infrared diagnostic apparatus.Other diagnostic methods,such as B-mode ultrasound,X-ray mammography,needle biopsy and pathological examination were,if necessary,used to further confirm the diagnosis.The screening showed that 5990 of 17618 cases (34.00％) had breast diseases,5843 (33.16％) had mammary gland hyperplasia,48 (0.27％) had breast fibroadenoma,ll (0.06％) had breast carcinoma,and 88 (0.50％) had other breast diseases.The peak morbidity of breast cancer was found in the women aged 50-0 ages.The morbidity of breast cancer was significantly increased in women elder than or equal to 50 years old (n=8,0.157％) in comparison with that in the subjects younger than 50 years old (n=3,0.024％) (u=2.327,P＜0.05).It was shown that the occurrence of breast diseases was concentrated in women aged 20-40 years,while the total morbidity reached its peak at the age of 30 years and then decreased sharply after age of 40.Compared with the patients elder than or equal to 40 years old (n=3289,27.46％),the morbidity rate of breast diseases was significantly increased in women less than 40 years old (2648 cases,47.18％; P＜0.001).However,there was no significant difference in the morbidity of breast diseases between the age group of 20-29 years and that of 30-39 years (P=0.453),and both of them were high.There was no significant association between the morbidity of breast diseases and cervical cancer.Since the morbidity of breast diseases was higher among young women,more attention should be paid to the screening of breast diseases among young women for early diagnosis.