EA-Net: Research on skin lesion segmentation method based on U-Net.

Accurate segmentation of skin lesions is a challenging task because the task is highly influenced by factors such as location, shape and scale. In recent years, Convolutional Neural Networks (CNNs) have achieved advanced performance in automated medical image segmentation. However, existing CNNs have problems such as inability to highlight relevant features and preserve local features, which limit their application in clinical decision-making. This paper proposes a CNN with an added attention mechanism (EA-Net) for more accurate medical image segmentation.EA-Net is based on the U-Net network model framework. Specifically, we added a pixel-level attention module (PA) to the encoder section to preserve the local features of the image during downsampling, making the feature maps input to the decoder more relevant to the ground-truth. At the same time, we added a spatial multi-scale attention module (SA) after the decoding process to increase the spatial weight of the feature maps that are more relevant to the ground-truth, thereby reducing the gap between the output results and the ground-truth. We conducted extensive segmentation experiments on skin lesion images from the ISIC 2017 and ISIC 2018 datasets. The results demonstrate that, when compared to U-Net, our proposed EA-Net achieves an average Dice score improvement of 1.94% and 5.38% for skin lesion tissue segmentation on the ISIC 2017 and ISIC 2018 datasets, respectively. The IoU also increases by 2.69% and 8.31%, and the ASSD decreases by 0.3783 pix and 0.5432 pix, indicating superior segmentation performance. EA-Net can achieve better segmentation results when the original image of skin lesions has an obscure boundary and the segmentation area contains interference factors, which proves that the addition of attention mechanism in the encoder and the application of comprehensive attention mechanism can improve the performance of neural network in the field of skin lesions image segmentation.

Brain tumor feature extraction and edge enhancement algorithm based on U-Net network.

Background: Statistics show that each year more than 100,000 patients pass away from brain tumors. Due to the diverse morphology, hazy boundaries, or unbalanced categories of medical data lesions, segmentation prediction of brain tumors has significant challenges. Purpose: In this thesis, we highlight EAV-UNet, a system designed to accurately detect lesion regions. Optimizing feature extraction, utilizing automatic segmentation techniques to detect anomalous regions, and strengthening the structure. We prioritize the segmentation problem of lesion regions, especially in cases where the margins of the tumor are more hazy. Methods: The VGG-19 network structure is incorporated into the coding stage of the U-Net, resulting in a deeper network structure, and an attention mechanism module is introduced to augment the feature information. Additionally, an edge detection module is added to the encoder to extract edge information in the image, which is then passed to the decoder to aid in reconstructing the original image. Our method uses the VGG-19 in place of the U-Net encoder. To strengthen feature details, we integrate a CBAM (Channel and Spatial Attention Mechanism) module into the decoder to enhance it. To extract vital edge details from the data, we incorporate an edge recognition section into the encoder. Results: All evaluation metrics show major improvements with our recommended EAV-UNet technique, which is based on a thorough analysis of experimental data. Specifically, for low contrast and blurry lesion edge images, the EAV-Unet method consistently produces forecasts that are very similar to the initial images. This technique reduced the Hausdorff distance to 1.82, achieved an F1 score of 96.1%, and attained a precision of 93.2% on Dataset 1. It obtained an F1 score of 76.8%, a Precision of 85.3%, and a Hausdorff distance reduction to 1.31 on Dataset 2. Dataset 3 displayed a Hausdorff distance cut in 2.30, an F1 score of 86.9%, and Precision of 95.3%. Conclusions: We conducted extensive segmentation experiments using various datasets related to brain tumors. We refined the network architecture by employing smaller convolutional kernels in our strategy. To further improve segmentation accuracy, we integrated attention modules and an edge enhancement module to reinforce edge information and boost attention scores.

Association of anxiety, depression symptoms and sleep quality with chronic kidney disease among older Chinese.

This study aimed to explore the association of anxiety, depression symptoms and sleep quality with chronic kidney disease (CKD) among older Chinese adults. A total of 1025 participants from the Chinese Longitudinal Healthy Longevity Survey (CLHLS, 2011-2012) were included in our study. The Generalized Anxiety Disorder scale was used to assess anxiety and the Center for Epidemiologic Studies Depression Scale was used to evaluate depressive symptoms. Logistic regression models were conducted to explore the odds ratios (ORs) and 95% confidential intervals (CIs). We found that anxiety, depression symptoms and poor sleep quality were positively associated with albuminuria, impaired estimated glomerular filtration (eGFR) and CKD, after adjusting for other covariates. For anxiety symptom, the ORs and 95% CIs were 1.20 (1.15-1.38) for albuminuria, 1.16 (1.12-1.35) for impaired eGFR and 1.18 (1.12-1.36) for CKD, respectively. For depression symptom, the ORs and 95% CIs were 1.15 (1.05-1.23) for albuminuria, 1.14 (1.05-1.20) for impaired eGFR and 1.14 (1.05-1.22) for CKD, respectively. Compared with good sleep quality, the OR and 95% CI of poor sleep quality were 1.12 (1.04-1.35) for albuminuria, 1.10 (1.02-1.30) for impaired eGFR and 1.11 (1.03-1.32) for CKD, respectively. And the positive association was more evident among females, body mass index ≥ 28, smoking and drinking adults. Anxiety, depression symptoms and poor sleep quality are positively associated with CKD. Future cohort studies are needed to confirm the results.

Sociodemographic features associated with the MoCA, SPPB, and GDS scores in a community-dwelling elderly population.

BACKGROUND: An accurate evaluation of cognitive function, physical health, and psychological health is fundamental for assessing health problems in the elderly population, and it is important to identify the necessity of early therapeutic intervention. The objective of this study was to evaluate the states of mental and physical functions and to investigate the relationships between sociodemographic features and these functions in a community-dwelling elderly population. METHODS: This community-based cross-sectional study was conducted in a suburban district of Shanghai, China. A total of 1025 participants aged 60-89 years underwent investigations of demographic and lifestyle features and a multidimensional geriatric evaluation comprising the Montreal Cognitive Assessment (MoCA), Short Physical Performance Battery (SPPB), and Geriatric Depression Scale (GDS). RESULTS: The results of the multivariate linear regression models demonstrated that the MoCA and SPPB scores decreased with advancing age (all P < 0.01). However, the GDS score did not exhibit an age-related decrease (P = 0.09). Both sex and living alone influenced the MoCA score (P < 0.01 and P = 0.04, respectively), SPPB score (P < 0.01 and P = 0.04, respectively), and GDS score (P < 0.01 and P < 0.01, respectively). A higher education level was related to better MoCA and SPPB scores (all P < 0.01). Furthermore, age and sex had interactive effects on the MoCA score (P = 0.03) and SPPB score (P < 0.01). The kernel-weighted local polynomial smoothing curves exhibited similar trends. CONCLUSIONS: It is imperative to develop a more sensitive evaluation of physical function, and to encourage various intellectually and emotionally stimulating social activity strategies to promote healthy aging, especially in elderly women and those living alone who have a low education level.

Foreign Body Granuloma Originating From the Lateral Process of Malleus: A Case Series of 19 Children.

OBJECTIVE: A special presentation of foreign body granuloma originating from the lateral process of the malleus (FBGLP) was noted in the absence of a history of foreign body entry into the external auditory canal (EAC). This study reported the clinical features, pathology, and prognosis of patients with FBGLP. DESIGN: Retrospective study. SETTING: Shandong Provincial ENT Hospital. PATIENTS: Nineteen pediatric patients (age, 1-10 yr) with FBGLP. INTERVENTIONS: Clinical data were collected from January 2018 to January 2022. MAIN OUTCOME MEASURES: Clinicopathologic characteristics of the patients were analyzed. RESULTS: All patients had an acute course, and were within 3 months of ineffective medical treatment. The most common symptoms were suppurative (57.9%) and hemorrhagic (42.1%) otorrhea. FBGLP imaging examinations demonstrated a soft mass blocking the EAC without bone destruction and occasionally concomitant effusion in the middle ear. The most common pathologic findings were foreign body granuloma (94.7%,18/19), granulation tissue (73.7%, 14/19), keratotic precipitate (73.7%, 14/19), calcium deposition (63.2%, 12/19), hair shafts (47.4%, 9/19), cholesterol crystals (5, 26.3%), and hemosiderin (15.8%, 3/19). Foreign body granuloma and granulation tissue showed higher expression levels of CD68 and cleaved caspase-3 than did the normal tympanic mucosa, whereas Ki-67 levels were similarly low in all tissues. The patients were followed up for 3 months to 4 years without recurrence. CONCLUSION: FBGLP is caused by endogenous foreign particles in the ear. We recommend the trans-external auditory meatus approach for FBGLP surgical excision, as this shows promising outcomes.

Identification of essential proteins based on edge features and the fusion of multiple-source biological information.

BACKGROUND: A major current focus in the analysis of protein-protein interaction (PPI) data is how to identify essential proteins. As massive PPI data are available, this warrants the design of efficient computing methods for identifying essential proteins. Previous studies have achieved considerable performance. However, as a consequence of the features of high noise and structural complexity in PPIs, it is still a challenge to further upgrade the performance of the identification methods. METHODS: This paper proposes an identification method, named CTF, which identifies essential proteins based on edge features including h-quasi-cliques and uv-triangle graphs and the fusion of multiple-source information. We first design an edge-weight function, named EWCT, for computing the topological scores of proteins based on quasi-cliques and triangle graphs. Then, we generate an edge-weighted PPI network using EWCT and dynamic PPI data. Finally, we compute the essentiality of proteins by the fusion of topological scores and three scores of biological information. RESULTS: We evaluated the performance of the CTF method by comparison with 16 other methods, such as MON, PeC, TEGS, and LBCC, the experiment results on three datasets of Saccharomyces cerevisiae show that CTF outperforms the state-of-the-art methods. Moreover, our method indicates that the fusion of other biological information is beneficial to improve the accuracy of identification.

Extracting transition features among brain states based on coarse-grained similarity measurement for autism spectrum disorder analysis.

BACKGROUND: The abnormal brain functional connectivity (FC) of patients with mental diseases is closely linked to the transition features among brain states. However, the current research on state transition will produce certain division deviations in the measurement method of state division, and also ignore the transition features among multiple states that contain more abundant information for analyzing brain diseases. PURPOSE: To investigate the potential of the proposed method based on coarse-grained similarity measurement to solve the problem of state division, and consider the transition features among multiple states to analyze the FC abnormalities of autism spectrum disorder (ASD) patients. METHODS: We used resting-state functional magnetic resonance imaging to examine 45 ASD and 47 healthy controls (HC). The FC between brain regions was calculated by the sliding window and correlation algorithm, and a novel coarse-grained similarity measure method was used to cluster the FC networks into five states, and then extract the features both of the state itself and the transition features among multiple states for analysis and diagnosis. RESULTS: (1) The state as divided by the coarse-grained measurement method improves the diagnostic performance of individuals with ASD compared with previous methods. (2) The transition features among multiple states can provide complementary information to the features of the state itself in the ASD analysis and diagnosis. (3) ASD individuals have different brain state transitions than HC. Specifically, the abnormalities in intra- and inter-network connectivity of ASD patients mainly occur in the default mode network, the visual network, and the cerebellum. CONCLUSIONS: Such results demonstrate that our approach with new measurements and new features is effective and promising in brain state analysis and ASD diagnosis.

Investigating continuation of folic acid supplementation during peri-conceptional period: a community-based cross-sectional study.

BACKGROUND: Maternal folate may not reach an optimal level to prevent neural tube defects if supplementation commenced post-conception or took place pre-conception only. Our study aimed to investigate the continuation of folic acid (FA) supplementation from pre-conception to post-conception during peri-conceptional period and to examine its differences in FA supplementation between the subgroups taking the initiation timing into consideration. METHODS: This study was conducted in two community health service centers in Jing-an District of Shanghai. Women accompanying their children to pediatric health clinics of the centers were recruited and asked to recall information concerning their socioeconomic and previous obstetric characteristics, utilization of healthcare and FA supplementation before and/or during pregnancy. The continuation of FA supplementation during peri-conceptional period were categorized into three subgroups: Supplementing with FA pre- and post-conception; supplementing with FA preconception only or post-conception only; no FA supplements pre-conception and post-conception. The relationship between FA continuation and couples' characteristics were examined as setting the first subgroup as the base reference. RESULTS: Three hundred and ninety-six women were recruited. Over 40% of the women started FA supplementation after conception and 30.3% of them supplemented with FA from pre-conception to the first trimester of their pregnancy. Compared to this one-third of participants, women who didn't supplemented with any FA during peri-conceptional period were more likely to have no utilization of pre-conception healthcare ([Formula: see text]= 2.47, 95% [Formula: see text]: 1.33-4.61) or antenatal care ([Formula: see text]= 4.05, 95% [Formula: see text]: 1.76-9.34), or who had a lower family socioeconomic status ([Formula: see text]= 4.36, 95% [Formula: see text]: 1.79-10.64). Women who supplemented with FA pre-conception only or post-conception only were more likely to have no utilization of pre-conception healthcare ([Formula: see text]= 2.94, 95% [Formula: see text]: 1.79-4.82), or to have no previous pregnancy complication ([Formula: see text]=1.80, 95% [Formula: see text]: 0.99-3.28). CONCLUSION: Over two-fifth of the women started FA supplementation and only one-third of them had an optimal supplementation from pre-conception to the first trimester. Maternal utilization of healthcare before or during pregnancy together with maternal and paternal socioeconomic status may play a role in the continuation to FA supplementation pre- and post-conception.

Surfactant Protein A can Affect the Surface Tension of the Eustachian Tube and Macrophage Migration.

OBJECTIVE: To assess the role and possible mechanism of surfactant protein A (SPA) in the pathogenesis of otitis media with effusion (OME). METHODS: This was a multi-part study with both an in vivo mouse model study as well as an in vitro study. The control and study groups (OME group) received phosphate-buffered saline and inactivated Streptococcus pneumoniae, respectively, via external auditory meatus injections. Changes in the surface tension of secretions from the eustachian tube (ET) and SPA expression were measured in both groups. A transwell assay was performed to observe the effect of different concentrations of SPA on the migration ability of macrophages. We examined the differentially expressed genes related to SPA-treated macrophages using RNA-seq analysis. RESULTS: On Day 3, the surface tension of the OME group was higher than that of the control group (p = 0.014). The variation intensity of SPA in the ET of the OME group was significantly lower than that of the control group (p < 0.001). Surface tension was correlated with SPA (r = -0.525, p = 0.037). The expression of SPA and macrophages in the ET was different between the two groups. In vitro experiments revealed that macrophages showed different migration abilities with SPA concentration changes (p < 0.05). RNA-seq and western blotting were performed after macrophages were treated with SPA. The results showed that RhoA and Rac1/2/3 were differentially expressed. CONCLUSIONS: SPA can change the surface tension of secretions from the ET and affect macrophage migration to alter the function of the ET. Although research in this field of OME is nascent, initial work suggests that SPA likely plays an important role in OME progression. LEVEL OF EVIDENCE: NA Laryngoscope, 133:1726-1733, 2023.

Predictive plasma biomarker for gestational diabetes: A case-control study in China.

OBJECTIVE: This study aims to find new plasma biomarkers in early pregnancy. DESIGN: The original study enrolled 1219 pregnant women. We investigated protein expression profiles of placental tissues from women with GDM (n = 89) and normal glucose tolerance (NGT) (n = 83). Maternal plasma samples between two groups in early and middle pregnancy were used for validation of candidate biomarkers. METHODS: Differentially expressed proteins (DEPs) were identified by label-free quantitative proteomics from human placenta samples between two groups. Several DEPs were validated in plasma by Luminex assays. An automatic biochemical analyzer was used to detect blood lipid indexes. The associations of GAL-3BP with biochemical indicators were demonstrated by Pearson's correlation analysis. Binary logistic regression was used to model potential predictive indicators in early pregnancy of GDM. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic accuracy of the predictive model and the value of GAL-3BP. RESULTS: 123 DEPs were found in placenta involved in ribosomal function, pancreatic secretion, oxidative phosphorylation, and inflammatory signaling pathway. Plasma GAL-3BP are significantly higher in women with GDM than NGT in the first (p = 0.008) and second (p = 0.026) trimester, but C9 and VWF have no difference. The predictive value of GAL-3BP in the first trimester of pregnancy (AUC 0.64) is better than that in the second trimester (AUC 0.61), and combined predictive model of TG and GAL-3BP at early pregnancy has greater predictive and diagnostic value for GDM (AUC 0.69) than individual GAL-3BP (AUC 0.64). CONCLUSIONS: Plasma TG and GAL-3BP has good predictive and diagnostic value at early pregnancy, suggesting that these two indicators may be used as biomarkers for early prediction and diagnosis of GDM. SIGNIFICANCE: The advantage of this study is that circulating TG and GAL-3BP might differentiate the progress of women with GDM and normal glucose tolerance (NGT) at the early stage of pregnancy. It is the first study to consider the role of GAL-3BP as an early predictive biomarker in the development of GDM during the whole pregnancy. Another advantage is that volunteers in this study were recruited from two provinces in China to eliminate the impacts of environmental confounders. The similar changes of blood glucose/lipid indicators for women with GDM and NGT in both regions was found in the first and second trimester of pregnancy, which added to the reliability of analytical results.

Generative adversarial networks with adaptive normalization for synthesizing T2-weighted magnetic resonance images from diffusion-weighted images.

Recently, attention has been drawn toward brain imaging technology in the medical field, among which MRI plays a vital role in clinical diagnosis and lesion analysis of brain diseases. Different sequences of MR images provide more comprehensive information and help doctors to make accurate clinical diagnoses. However, their costs are particularly high. For many image-to-image synthesis methods in the medical field, supervised learning-based methods require labeled datasets, which are often difficult to obtain. Therefore, we propose an unsupervised learning-based generative adversarial network with adaptive normalization (AN-GAN) for synthesizing T2-weighted MR images from rapidly scanned diffusion-weighted imaging (DWI) MR images. In contrast to the existing methods, deep semantic information is extracted from the high-frequency information of original sequence images, which are then added to the feature map in deconvolution layers as a modality mask vector. This image fusion operation results in better feature maps and guides the training of GANs. Furthermore, to better preserve semantic information against common normalization layers, we introduce AN, a conditional normalization layer that modulates the activations using the fused feature map. Experimental results show that our method of synthesizing T2 images has a better perceptual quality and better detail than the other state-of-the-art methods.

Identifying depression disorder using multi-view high-order brain function network derived from electroencephalography signal.

Brain function networks (BFN) are widely used in the diagnosis of electroencephalography (EEG)-based major depressive disorder (MDD). Typically, a BFN is constructed by calculating the functional connectivity (FC) between each pair of channels. However, it ignores high-order relationships (e.g., relationships among multiple channels), making it a low-order network. To address this issue, a novel classification framework, based on matrix variate normal distribution (MVND), is proposed in this study. The framework can simultaneously generate high-and low-order BFN and has a distinct mathematical interpretation. Specifically, the entire time series is first divided into multiple epochs. For each epoch, a BFN is constructed by calculating the phase lag index (PLI) between different EEG channels. The BFNs are then used as samples, maximizing the likelihood of MVND to simultaneously estimate its low-order BFN (Lo-BFN) and high-order BFN (Ho-BFN). In addition, to solve the problem of the excessively high dimensionality of Ho-BFN, Kronecker product decomposition is used for dimensionality reduction while retaining the original high-order information. The experimental results verified the effectiveness of Ho-BFN for MDD diagnosis in 24 patients and 24 normal controls. We further investigated the selected discriminative Lo-BFN and Ho-BFN features and revealed that those extracted from different networks can provide complementary information, which is beneficial for MDD diagnosis.

Whole-exome sequencing reveals novel variants associated with abnormal uterine bleeding caused by copper intrauterine device.

Aim: This study aimed to explore the genetic risk factors and validate variants of abnormal uterine bleeding after copper intrauterine device insertion. Methods: Whole-exome sequencing was performed and several variants were validated by Sequenom MassARRAY. Results: Eight variants showed potential clinical damage according to American College of Medical Genetics and Genomics criteria. By combined analysis of screening and validation, NFASC RS2802808 C>G p.Ile971Met (Pallele = 0.009 and Pgenotype = 0.027) and PIGR RS2275531 C>T p.Gly365Ser (Pallele = 0.009 and Pgenotype = 0.013) variants were identified as significantly associated with abnormal uterine bleeding with a false discovery rate <0.05. NFASC and PIGR may play a role in abnormal uterine bleeding by regulating coagulation fibrinolysis and endometrial epithelium inflammation functions. Conclusion: These findings provide a genetic basis for clinical individualization and precision of intrauterine device implantation.

Abnormal uterine bleeding (AUB) after Cu intrauterine device (Cu-IUD) insertion is the most common side effect of Cu-IUD use. AUB is a multifactorial process that relates to endometrial-related genetic factors, ovulatory function-related genetic factors, coagulation, the fibrinolytic system, contraction of the uterine arteries and endometritis inflammatory factor. This is the first study to explore the underlying genetic mechanisms of AUB related to the use of Cu-IUDs by whole-exome sequencing in the Chinese Han population. The authors found that variants of NFASC and PIGR genes were significantly associated with AUB in women using Cu-IUDs. NFASC and PIGR may be involved in coagulation fibrinolysis and endometrial epithelium inflammation functions, indicating its potential functions in AUB. This study could provide a genetic basis for studies on the individualization and precision of IUD use in the future.

Prevalence of reproductive tract infections among women preparing to conceive in Chongqing, China: trends and risk factors.

BACKGROUND: Reproductive tract infection has become a major public health issue all over the world for its high and growing prevalence. It can cause adverse pregnancy outcomes in pregnant women and their foetuses. This study aimed to investigate the trends and risk factors of the prevalence of reproductive tract infections among women who prepared to conceive in the Chongqing Municipality (China) from 2012 to 2016. METHODS: A multi-center cross-sectional study was conducted between January 2012 and December 2016. Women aged 20-49 years who intended to get pregnant were recruited for this study. All participants underwent preconception examination, which included testing for Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, syphilis, bacterial vaginosis and candidiasis according to the national diagnostic standard. A total of 439,372 women with testing results for all six types of reproductive tract infections were included in our final analyses. Logistic regression and factor analysis were used to determine the possible sociodemographic factors associated with prevalence trends. RESULTS: In our study, the overall positive rate of RTIs among the 439,372 women of reproductive age was 5.03%. Candidiasis was the most common infection in our population (2.47%), followed by bacterial vaginosis (1.28%), syphilis (0.73%), T. vaginalis (0.49%), C. trachomatis (0.20%) and N. gonorrhoeae (0.06%). The prevalence of reproductive tract infections was highest among women aged 35 years and above, with a primary or lower education level, history of pregnancy, delivery, induced abortion, or spontaneous abortion. From 2012 to 2016, the trend of the overall prevalence of reproductive tract infections was V-shaped, decreasing steadily from 2012 to 2015, with a slight rise in 2016. Our results suggest that the distribution change of age, education level, gravidity, parity, and history of induced abortion influenced this trend. CONCLUSION: Since the number of high-risk women who intend to become pregnant is growing in the Chongqing Municipality, pre-conception positive preventions including health education, regular screening, and timely treatment of reproductive tract infections are needed to prevent the impact of reproductive tract infections on maternal health and infant safety.

Reproductive tract infections (RTIs) can cause serious health problems, such as spontaneous abortion and congenital diseases in pregnant women and their foetuses. However, there is a lack of studies focusing on the prevalence of RTIs and their trends among women who intend to conceive. This cross-sectional study examined data collected from 439,372 women during their preconception care to investigate the trend and related risk factors of the prevalence of RTIs, thereby providing essential data for their prevention. Participants were women from all 39 counties in the Chongqing Municipality of China, and data were collected between 2012 and 2016. We found that the overall prevalence of the six types of RTIs among these women was 5.03%, which was relatively lower than that in other populations in previous studies. Age, education level, history of pregnancy or delivery, and history of abortion were all associated with the prevalence of RTIs. The prevalence trend from 2012 to 2016 was V-shaped decreased steadily from 2012 until 2015 and rose slightly in 2016. Our data suggested that this trend might be influenced by changes in the proportion of 'high-risk' women, that is, women with higher age, lower education level, and a history of pregnancy or induced abortion. This study suggests that health education and regular screening are necessary to face new challenges experienced by older women or women with previous pregnancies who intended to get pregnant in recent years in China.

Integrated single-cell RNA-seq and DNA methylation reveal the effects of air pollution in patients with recurrent spontaneous abortion.

BACKGROUND: Maternal air pollutants exposure is associated with a number of adverse pregnancy outcomes, including recurrent spontaneous abortion (RSA). However, the underlying mechanisms are still unknown. The present study aimed to understand the mechanism of RSA and its relationship with air pollution exposure. We compared data of decidual tissue from individuals with induced abortions and those with RSA by bulk RNA sequencing (RNA-seq), reduced representation bisulfite sequencing (RRBS), and single-cell RNA sequencing (scRNA-seq). Differentially expressed genes (DEGs) were verified using RT-qPCR and pyrosequencing. A logistic regression model was used to investigate the association between air pollutants exposure and RSA. RESULTS: We identified 98 DEGs with aberrant methylation by overlapping the RRBS and RNA-seq data. Nineteen immune cell subsets were identified. Compared with normal controls, NK cells and macrophages accounted for different proportions in the decidua of patients with RSA. We observed that the methylation and expression of IGF2BP1 were different between patients with RSA and controls. Furthermore, we observed significant positive associations between maternal air pollutants exposure during the year prior to pregnancy and in early pregnancy and the risk of RSA. Mediation analyses suggested that 24.5% of the effects of air pollution on the risk of RSA were mediated through IGF2BP1 methylation. CONCLUSION: These findings reveal a comprehensive cellular and molecular mechanism of RSA and suggest that air pollution might cause pregnancy loss by affecting the methylation level of the IGF2BP1 promoter.

Placental DNA methylation changes in gestational diabetes mellitus.

In this study, we investigated the association between altered methylation in the maternal placenta and hyperglycaemia and explored the epigenetic mechanisms underlying gestational diabetes mellitus (GDM). Reduced representation bisulphite sequencing (RRBS) and RNA sequencing (RNA-seq) were performed on placental tissues obtained from women with GDM and healthy controls. Further, pyrosequencing, correlation analyses, and linear regression analyses were performed to valuate relationships between aberrantly methylated-differentially expressed genes and clinical parameters. The EMBOSS and JASPAR databases were used for a computational analysis of CpG islands and transcription factor-binding sites in the TRIM67 promoter region. A CpG island with a length of 264 bp in the placental TRIM67 promoter region in the GDM group exhibited significant hypermethylation at four CpG sites. The hypermethylation of the TRIM67 promoter region in the maternal placenta showed a significant, positive correlation with the 1 h and 2 h oral glucose tolerance test (OGTT) values and a negative correlation with lipoprotein(a). Placental DNA methylation levels in the TRIM67 promoter region were markedly elevated in GDM and were associated with blood glucose and lipid levels during healthy pregnancy.

Preconception reproductive tract infections status and adverse pregnancy outcomes: a population-based retrospective cohort study.

BACKGROUND: Reproductive tract infections can cause serious adverse outcomes for pregnant women such as spontaneous abortion and preterm birth. However, it is unclear whether maternal reproductive tract infection before pregnancy would also be related to any adverse pregnancy outcomes. This study aims to investigate the association of maternal preconception reproductive tract infections with subsequent adverse pregnancy outcomes. METHODS: A retrospective cohort study was conducted in the Chongqing Municipality of China between April 2010 and December 2016. A total of 57,586 women (57,708 pregnancies) from all 39 counties of Chongqing who participated in the National Free Preconception Health Examination Project were included. They all took preconception examinations for gonorrhea, chlamydia, trichomoniasis, syphilis, bacterial vaginosis and candidiasis before pregnancy within one year. Primary outcomes included spontaneous abortion (< 28 weeks gestation), preterm birth (< 37 weeks gestation), macrosomia and low birthweight. RESULTS: Of the 57,708 pregnancies, 2438 (4.22%) had at least one type of reproductive tract infections. Compared with women who were not infected with any reproductive tract infection before pregnancy, women with reproductive tract infections had a higher rate of spontaneous abortion (7.88% vs. 5.62%, p < 0.001). After analyzing by each infection, there were few significant associations between pre-pregnancy infections and adverse outcomes. Preconception syphilis infection was significantly associated with increased odds of spontaneous abortion (aOR = 2.07, 95%CI 1.50-2.85), induced abortion/labour due to medical reasons (aOR = 1.60, 95%CI 1.01-2.54) and preterm birth (aOR = 1.60, 95%CI 1.12-2.30) after adjusting for potential confounders. Preconception trichomoniasis was intended to relate to a higher risk of spontaneous abortion (aOR = 1.65, 95%CI 1.01-2.71), but its impact seemed to be attributed to its co-infection with other RTIs. Women who were chlamydia or bacterial vaginosis positive before pregnancy showed higher odds of macrosomia (aOR = 2.00, 95% CI 1.07-3.74 for chlamydia; aOR = 1.58, 95% CI 1.06-2.34 for bacterial vaginosis). Preconception bacterial vaginosis might also be associated with higher risks of very preterm birth (aOR = 2.16, 95%CI 1.23-3.78) and large for gestational age (aOR = 1.36, 95%CI 1.02-1.81). CONCLUSIONS: Women with infections of the genital tract before pregnancy might also have increased risks of subsequent adverse outcomes including spontaneous abortion, preterm birth and macrosomia.

Clinical observation of posterior scleral reinforcement in the treatment of progressive high myopia in Chinese children: a retrospective study.

OBJECTIVE: To observe the efficacy and safety of posterior sclera reinforcement over time. METHODS: This retrospective single-arm cohort study included children with high myopia who underwent the modified Snyder-Thompson type posterior sclera reinforcement surgery from 03/2015 to 08/2018 at Fuzhou Children's Hospital of Fujian Medical University. Axial length (AL), corneal radius of curvature (CRC), AL/CRC, refractive error, and best-corrected visual acuity (BCVA) were observed from 1 year before the operation to 2 years after. RESULTS: Nineteen children (33 eyes) with high myopia were included. The patients were 4.9 ± 2.7 (range, 2-10) years of age (three patients were 10 years old, all others were ≤ 7 years old). AL increased from 1 year before surgery to 2 years after surgery (from 25.31 ± 1.59 to 26.76 ± 1.52, P < 0.001). The refractive error was smaller 1 year before surgery than at the other timepoints (all P < 0.05). BCVA improved over time (P < 0.001). Changes over time were also observed in horizontal CRC (hCRC), AL/hCRC, AL/vertical CRC (vCRC), and AL/CRC (all P < 0.001), but not in vCRC (P = 0.304). The increase of AL at 2 years after surgery was smaller than at 1 year before surgery and 1 year after surgery (both P < 0.001). The increase of AL/CRC at 2 years after surgery was smaller than at 1 year before surgery (0.04 ± 0.04 vs. 0.07 ± 0.04; P = 0.008). CONCLUSION: In the short term, posterior scleral reinforcement surgery can delay the increase of AL of progressive high myopia.

The Alterations and Significance of Intercellular Adhesion Molecule-1 in Mouse Brainstem During Herpes Simplex Virus Type 1-Induced Facial Palsy.

Herpes simplex virus type 1 (HSV-1) results in the development of Bell's pals but still, the pathophysiology of the facial nerve paralysis is still not fully studied. The main objective is to establish an animal model of type 1 herpes simplex virus (HSV-1)-induced face paralysis in the mouse and to investigate the pattern of changes in intercellular adhesion molecule -1(ICAM-1) expression in the facial nucleus of the brain stem in mice with facial paralysis as well as the effects of glucocorticoids on intercellular adhesion molecule -1(ICAM-1) expression. A total of 170 4-week-old Balb/c male mice were randomly divided into the virus inoculation group (n = 135), saline control group (n = 26), and blank control group (n = 9). Mice in the virus inoculation group that showed facial paralysis were divided into A, B, and C subgroups. The A group did not receive any treatments, the B group received methylprednisolone sodium succinate (MPSS) intervention, and the C group received MPSS + RU486 treatment. The mouse model of facial paralysis was established by inoculating HSV-1 to the skin at the back of the ears. The facial nerve function of mice was assessed, and real-time PCR and western blot were used to assess ICAM-1 expression in the facial nucleus of the brain stem in mice with facial paralysis after drug intervention. In the virus inoculation group, 95 mice (55.88%) showed varying degrees of facial paralysis symptoms within 2-5 days after inoculation. The ICAM-1 gene and protein expression levels remained at low levels in the facial nucleus of the brain stem of mice in the saline group, which showed no significant difference compared to the normal control group (P > 0.05). However, for mice of the virus inoculation group, ICAM-1 expression increased at 6 h after the occurrence of facial paralysis and peaked after 2 days, differing significantly from the blank control group (P < 0.01). ICAM-1 expression subsequently decreased gradually. In the HSV-1 + MPSS group, ICAM-1 protein expression decreased significantly on the 2nd day after facial paralysis. In the HSV-1 + MPSS + RU486 group, MPSS inhibition of ICAM-1 protein expression was reduced. The results suggested that ICAM-1 is involved in the pathological processes by which HSV-1 induces facial paralysis in mice, and the treatment effects of MPSS for Bell's palsy can be achieved by the inhibition of MCP-1.

Associations of MCM8 rs3761873 and rs16991617 variants with abnormal uterine bleeding induced by copper intrauterine device.

AIM: Intrauterine device (IUD) is a commonly used contraceptive method worldwide. Abnormal uterine bleeding (AUB) is one of the most common side effects of Cu-IUDs. Since AUB varies among Cu-IUD users, changes in the bleeding-related genetic factors may contribute to AUB. This study aimed to determine the genetic risk factors of AUB after Cu-IUD insertion. METHODS: We conducted a case-control study on women who experienced AUB after Cu-IUD insertion (case:control = 62:59). Six candidate variants were genotyped using the Sequenom MassARRAY. Genotype and allele frequencies were analyzed using SHEsisPlus. We performed Pearson's Chi-squared test to analyze categorical data, and ESEfinder to predict the impact on splicing regulation. RESULTS: MCM8 coding sequence variants: rs3761873-A>C was in Exon 7 and rs16991617 A>G was in Exon 12 of all 19 exons, both of which were significantly different between cases and controls (pallele  = 0.039 and pgenotype  = 0.092). rs6022 and rs6029 in F5 gene and rs3761873 and rs16991617 in the MCM8 gene showed strong linkage disequilibrium (R2 > 0.8). ESEfinder indicated that the variants of MCM8 may affect the splicing regulation. CONCLUSIONS: MCM8 rs376187 and rs16991617 were associated with AUB in Cu-IUDs users. MCM8 may play a role in AUB by regulating functions of reproductive organs and primary ovarian insufficiency. Our findings may improve the understanding of the genetic basis of AUB caused by Cu-IUDs.