Downregulated PDIA3P1 lncRNA Impairs Trophoblast Phenotype by Regulating Snail and SFRP1 in PE.

Preeclampsia (PE) manifests as a pregnancy-specific complication arising from compromised placentation characterized by inadequate trophoblast invasion. A growing body of evidence underscores the pivotal involvement of pseudogenes, a subset of long noncoding RNAs, in the pathological processes of PE. This study presents a novel finding, demonstrating a significant downregulation of the pseudogene PDIA3P1 in PE placental tissues compared to normal tissues. In vitro functional assays revealed that suppressing PDIA3P1 hindered trophoblast proliferation, invasion, and migration, concurrently upregulating the expression of secreted frizzled-related protein 1 (SFRP1). Further exploration of the regulatory role of PDIA3P1 in PE, utilizing human trophoblasts, established that PDIA3P1 exerts its function by binding to HuR, thereby enhancing the stability of Snail expression in trophoblasts. Overall, our findings suggest a crucial role for PDIA3P1 in regulating trophoblast properties and contributing to the pathogenesis of PE, offering potential targets for prognosis and therapeutic intervention.

Establishment and application of a rapid molecular diagnostic platform for the isothermal visual amplification of group B Streptococcus based on recombinase polymerase.

With growing concerns about Group B streptococcal (GBS) infections and their adverse effects on perinatal pregnancies, including infection, premature delivery, neonatal septicemia, and meningitis, it is urgent to promote GBS screening at all pregnancy stages. The purpose of this study is to establish a device-independent, fast, sensitive, and visual GBS detection method. Taking advantage of the characteristics of the recombinase polymerase isothermal amplification (RPA), the activity of the nfo nuclease cleavage base analog (tetrahydrofuran, THF) site, and the advantages of visual reading of the lateral flow chromatography strip (LFS), a GBS detection method was developed. This method focused on the conservative region of the Christie-Atkins-Munch-Petersen factor encoded by the cfb gene, a virulence gene specific to GBS. Two forward primers, two biotin-labeled reverse primers, and one fluorescein isothiocyanate (FITC)-labeled and C3spacer-blocked probe were designed. The study involved optimizing the primer pair and probe combination, determining the optimal reaction temperature and time, evaluating specificity, analyzing detection limits, and testing the method on 87 vaginal swabs from perinatal pregnant women. The results showed that the visual detection method of GBS-RPA-LFS, using the cfb-F1/R2/P1 primer probe, could detect GBS within 15 min at the temperature ranging from 39°C to 42°C. Furthermore, the method specifically amplified only GBS, without cross-reacting with pathogens like Lactobacillus iners, Lactobacillus crispatus, Candida albicans, Listeria monocytogenes, Yersinia enterocolitica, Klebsiella Pneumoniae, Enterobacter cloacae, Citrobacter freundii, Vibrio alginolyticus, Vibrio parahaemolyticus, Salmonella typhimurium, Staphylococcus aureus, Pseudomonas aeruginosa, or Trichomonas vaginalis. It could detect a minimum of 100 copies per reaction. In clinical 98 samples of vaginal swabs from pregnant women, the agreement rate between the GBS-RPA-LFS method and TaqMan real-time fluorescence quantification method was 95.92%. In conclusion, this study successfully established a combined RPA and LFS GBS in situ detection platform, with short reaction time, high sensitivity, high specificity, portability, and device independence, providing a feasible strategy for clinical GBS screening.

DNA-Peptide Interaction-Modulated Charge Reversal in Biomimetic Nanochannels for Simple and Efficient Detection of Histone Deacetylases.

Protein acetylation, a fundamental post-translational modification, plays a critical role in the regulation of gene expression and cellular processes. Monitoring histone deacetylases (HDACs) is important for understanding epigenetic dynamics and advancing the early diagnosis of malignancies. Here, we leverage the dynamic characteristics of DNA-peptide interactions in biomimetic nanochannels to develop a HDAC detection method. In specific, the catalysis of peptide deacetylation by HDACs triggers alterations in the charge states of the nanochannel surface to accommodate DNA molecules. Then, the interaction between DNA and peptides shifts the nanochannel surface charge from positive to negative, leading to a reversal of the ion current rectification (ICR). By calculation of the ICR ratio, quantitative detection of HDACs can be efficiently achieved using the nanochannel-based method in an enzyme-free and label-free manner. Our experimental results demonstrate that HDACs can be detected by using this method within a concentration range of 0.5-500 nM. The innate simplicity and efficiency of this strategy may render it a valuable tool for advancing both fundamental research and clinical applications in the realm of epigenetics and personalized medicine.

Multicolor melting curve analysis discloses high carrier frequency of hearing loss-associated variants among neonates in Jiangsu province.

BACKGROUND: Genetic disorders ascribe to half of cases of congenital hearing loss. Hearing screening is significant in detecting hearing loss (HL) but weak at diagnosis, which can be complemented by genetic screening. METHODS: To find a feasible method to accomplish genetic screening and evaluate its advantage when combined with hearing screening, between 1 January 2022, and 10 December 2023, we performed an observational cohort study based on 2488 neonates from the Han population at three hospitals in Jiangsu province. Genetic screening for 20 variants in four common HL-associated genes by multicolor melting curve analysis (MMCA) and hearing screening were offered concurrently to all participants. RESULTS: In total, 170 (6.8%) of 2488 eligible neonates were detected at least one variant and among them, the proportion of referral was higher (p < 0.05). Genetic screening combined with hearing screening was associated with a 25.0% increase (2 of 8) in discovering cases of diagnosed hearing loss that were missed by hearing screening. CONCLUSION: This study suggests that genetic screening combined with hearing screening by MMCA is effective at finding potential HL cases and practical to be validated in other places.

Comparative peptidomics analysis of preeclamptic placenta and the identification of a novel bioactive SERPINA1 C-terminal peptide.

Preeclampsia (PE) is a life-threatening disease that severely harms pregnant women and infants' health but has a poorly understood etiology. Peptidomics can supply important information about the occurrence of diseases. However, application of peptidomics in preeclamptic placentas has never been reported. We conducted a comparative peptidomics analysis of PE placentas and performed bio-informatics analysis on differentially expressed peptides. Effects of differential peptide 405SPLFMGKVVNPTQK418 on the behaviors of trophoblasts and angiogenesis were assessed by CCK8, transwell assays, and tube network formation assays. And we also confirmed the role of peptide in the zebrafish xenograft model. A total of 3582 peptide were identified. 48 peptides were differentially expressed. Bioinformatics analysis indicated that precursor proteins of these differentially expressed peptides correlate with "complement and coagulation cascades," and "platelet activation" pathways. Of the 48 differential peptides, we found that peptide 405SPLFMGKVVNPTQK418 can significantly increase proliferation, migration of trophoblasts and stimulate angiogenesis of HUVECs in vitro and zebrafish model. These findings suggest peptidomes can aid in understanding the pathogenesis of PE more comprehensively. Peptide 405SPLFMGKVVNPTQK418 can be novel target and strategy to alleviate the condition of preeclampsia.

TET3-mediated novel regulatory mechanism affecting trophoblast invasion and migration: Implications for preeclampsia development.

INTRODUCTION: Aberrant expression of genes has been demonstrated to be related to the abnormal function of trophoblasts and lead to the occurrence and progression of Preeclampsia (PE). However, the underlying mechanism of PE has not been elucidated. METHODS: We performed PCR analysis to investigate TET3 expression in PE placental tissues. Cell assays were performed in HTR-8/SVneo and JAR. Cell invasion and migration events were investigated by transwell assays in vitro. ChIP-PCR and Targeted bisulfite sequencing were conducted to detect the demethylation of related CpG sites in the KLF13 promoter after inhibition of TET3. In conjunction with bioinformatics analysis, luciferase reporter assays were performed to elucidate the mechanism by which miR-544 binds to TET3/KLF13 mRNA. RESULTS: In this study, we identified genes associated with human extravillous trophoblasts by conducting sc-seq analysis from the GEO. Then, we measured the expression of TET3 in a larger clinical sample. The results showed that TET3, a DNA demethylase, was found to be expressed at much higher levels in the preeclamptic placenta compared to the control. Then, the inhibition of TET3 significantly promoted trophoblast cell migration and invasion. Conversely, TET3 overexpression suppressed cell migration and invasion in vitro. Further RNA sequencing and mechanism analysis indicated that the inhibition of TET3 suppressed the activation of KLF13 by reducing the demethylation of related CpG sites in the KLF13 promoter, thereby transcriptionally inactivating KLF13 expression. Moreover, luciferase reporter assay indicate that TET3 and KLF13 were direct targets of miR-544. DISCUSSION: This study uncovers a TET3-mediated regulatory mechanism in PE progression and suggests that targeting the placental miR-544-TET3-KLF13-axis might provide new diagnostic and therapeutic strategies for PE.

Identification of a novel de novo PUF60 variant causing Verheij syndrome in a fetus.

Verheij syndrome (VRJS) is a craniofacial spliceosomopathy with a wide phenotypic spectrum. Haploinsufficiency of the poly-uridine binding splicing factor 60 gene (PUF60) and its loss-of-function (LOF) variants are involved in VRJS. We evaluated a human fetus with congenital heart defects and preaxial polydactyly. Clinical data were obtained from the medical record. Whole-exome sequencing (WES) was used to explore the potential genetic etiology, and the detected variant verified using Sanger sequencing. Functional studies were performed to validate the pathogenic effects of the variant. Using trio-WES, we identified a novel PUF60 variant (NM_078480.2; c.1678 T > A, p.*560Argext*204) in the pedigree. Bioinformatic analyses revealed that the variant is potentially pathogenic, and functional studies indicated that it leads to degradation of the elongated protein and subsequently PUF60 LOF, producing some VRJS phenotypes. These findings confirmed the pathogenicity of the variant. This study implicates PUF60 LOF in the etiopathogenesis of VRJS. It not only expands the PUF60 variant spectrum, and also provides a basis for genetic counseling and the diagnosis of VRJS. Although trio-WES is a well-established approach for identifying the genetic etiology of rare multisystemic conditions, functional studies could aid in verifying the pathogenicity of novel variants.

Preparation of Well-Constructed and Metal-Modified Covalent Organic Framework Nanoparticles for Biosensing Design with Cascade Catalytic Capability.

Uniform covalent organic framework nanoparticles (COF NPs) with a well-defined pore structure may provide a robust platform for scaffolding enzymes. Herein, bipyridine-based spherical COF NPs have been successfully prepared in this work through the Schiff base condensation reaction. Moreover, they are functionalized by metal modification and are further used for biosensor fabrication. Experimental results reveal that the metal-modified COF NPs also display impressive peroxidase-like catalytic activities, while they can load enzymes, such as glucose oxidase (GOx) and sarcosine oxidase (SOx), to develop a cascade catalysis system for design of various kinds of biosensors with very well performance. For example, the optimized GOx@Fe-COFs can achieve a sensitive detection of glucose with a low limit of detection (LOD) of 12.8 µM. Meanwhile, the enzymes also exhibit a commendable preservation of 80% enzymatic activity over a span of 14 days under ambient conditions. This work may pave the way for advancing cascade catalysis and the analysis of different kinds of biological molecules based on COF NPs.

Prevalence and associated factors of insomnia symptoms among pregnant women in the third trimester in a moderately developing region of China.

BACKGROUND: Insomnia is the most common sleep disorder in the general population, especially among pregnant women, and it is considered a major public health issue. Not only can it cause mental and physical problems in pregnant women, but it may also affect the growth of the fetus. However, there are few reports on the prevalence and influencing factors of insomnia symptoms in third-trimester women in China. The objective of this study was to assess the prevalence of insomnia symptoms among pregnant women in the third trimester in a moderately developing region of China and to further explore the associated factors of insomnia symptoms from various aspects. METHODS: A cross-sectional survey was conducted among eligible pregnant women in the third trimester from December 2022 to February 2023. Data on socio-demographic characteristics, clinical characteristics, and behavioral and psychological characteristics of pregnant women were collected through a structured questionnaire. The Chi-square test and multivariate logistics regression were applied to explore the associated factors of insomnia symptoms. RESULTS: A total of 535 pregnant women in the third trimester were included in this study, and the prevalence of insomnia symptoms was 59.8%. Multivariate logistic regression analysis revealed that pregnant women who lived together with elders (OR: 0.58, 95% CI: 0.40-0.86), had low perceived stress (OR: 0.58, 95% CI: 0.35-0.97), had no threatened abortion (OR: 0.55, 95% CI: 0.32-0.93) and had good doctor-patient communication (OR: 0.66, 95% CI: 0.45-0.98) were more likely to stay away from insomnia symptoms. However, pregnant women with anxiety symptoms (OR: 2.27, 95% CI: 1.28-4.03), fear of childbirth (OR: 1.63, 95% CI: 1.11-2.40) and a high experience of COVID-19 fear (OR: 1.61, 95% CI: 1.03-2.54) tended to have insomnia symptoms. CONCLUSIONS: The prevalence of insomnia symptoms in pregnant women is high in Lianyungang city in eastern China in the third trimester. Insomnia symptoms is influenced by multiple factors. There is an urgent need to develop interventions to reduce the prevalence of insomnia symptoms in the third trimester and to focus on pregnant women with risk factors for insomnia symptoms.

Establishment and application of a point-of-care testing and diagnosis method for early immediate expression gene IE1 of cytomegalovirus in maternal urine based on isothermal amplification.

BACKGROUND: Human Cytomegalovirus virus (HCMV) is a worldwide virus that causes no serious symptoms in most adults. However, HCMV infection during pregnancy, it may lead to a series of serious complications, such as hearing loss, mental retardation, visual impairment, microcephaly and developmental retardation. AIM: The aim of this study was to develop a simple, low dependence on equipment and accurate method for HCMV detection based on the recombinase polymerase amplification (RPA) and lateral flow chromatography strip (LFS) reading. METHODS: In order to meet the feasibility of HCMV early screening, three pairs of RPA primers were designed based on the UL123 gene encoding IE1, which was expressed immediately in the early stage of HCMV. In order to improve the specificity of the reaction and satisfy the visual detection, a specific probe was designed to insert THF site between upstream and downstream primers, fluorescein isothiocyanate (FITC) and C3spacer were used to modify the 5' end and the 3' end respectively, and Biotin was used to modify the 5' end of the reverse primer. HCMV standard strain AD169 was enriched by ARPE-19 cells culture, and its genome was extracted. The primers and probes were screened by RPA-LFS test, and the optimal reaction temperature and time were determined The specificity was verified in different viruses, bacteria and parasites. The standard curve was drawn based on the constructed recombinant plasmid of pMD18T-HCMV-UL123 and used for HCMV genomic DNA quantification and determination of the detection sensitivity. Urine samples from artificial HCMV contamination or clinical collection were prepared to evaluate the consistency with the results of real-time quantitative PCR. RESULTS: The results showed that the primers and probes for HCMV RPA-LFS detection based on UL123 gene were successfully screened, the amplification of HCMV genomic DNA with as low as 30 copies could be completed at 37 °C within 15 min, it did not react with Human herpesvirus 1, Streptococcus pyogenes, Candida albicans, Listeria monocytogenes, Y. enterocolitica, Klebsiella Pneumoniae, Enterobacter cloacae, Citrobacter freundii, Vibrio alginnolyfificus, Vibrio parahaemolyticus, S. typhimurium, Staphylococcus aureus, Pseudomonas aeruginosa and Trichomonas vaginalis. The positive rate of PCR was 96.67 % in 30 simulated urine samples and 100 % in 127 clinical urine samples with the same UL123 gene detection. CONCLUSIONS: To sum up, we developed a diagnostic method for HCMV based on UL123 gene combined with RPA and LFS, which is low dependent on equipment, fast, sensitive and specific, provide reference for point-of-care testing HCMV in grass-roots laboratories and remote areas.

Fear of childbirth and its determinants in pregnant women in the third trimester: a cross-sectional study.

BACKGROUND: Fear of childbirth (FOC) is a prevalent issue among pregnant women and significantly relates to adverse outcomes for the mother and child. However, it is not clear the prevalence and risk factors of FOC among pregnant women in a region with a moderate level of economic development in China. The aim of this study was to investigate the prevalence and risk factors of FOC among pregnant women in the third trimester of pregnancy in Lianyungang city, Eastern China. METHODS: A cross-sectional survey was conducted from December 2022 to February 2023 among pregnant women in the third trimester who met the inclusion criteria and visited Lianyungang Maternal and Child Health Hospital in Jiangsu Province, Eastern China. A structured questionnaire including sociodemographic characteristics, clinical characteristics, FOC, family function, doctor-patient communication, social support, general self-efficacy, anxiety, depression, insomnia symptoms, and quality of life was used to collect data. A multiple linear regression model was used to identify predictors of FOC. RESULTS: This study included 535 pregnant women in the third trimester. The mean score of FOC was 30.67 ± 10.18, and the median score was 29.00. The prevalence of FOC was 56.64%. Multiple linear regression analysis revealed that pregnant women with electronic screen exposure time more than 5 h per day (ß = 2.02, 95%CI: 0.50-3.53, P < 0.05), no history of cesarean section (ß = 2.66, 95%CI: 0.61-4.71, P < 0.05), likes sour food or hates greasy food (ß = 1.75, 95%CI: 0.00-3.50, P < 0.05), anxiety (ß = 0.50, 95%CI: 0.21-0.80, P < 0.05) and depression (ß = 0.30, 95%CI: 0.04-0.57, P < 0.05) were more likely to have a greater level of FOC than their counterparts. However, a significantly lower level of FOC was observed in pregnant women who were multipara (ß=-1.64, 95%CI: -3.27-0.01, P < 0.05), not worrying about delivery without family members (ß=-3.75, 95%CI: -5.26-2.25, P < 0.001), had good family function (ß=-0.32, 95%CI: -0.64-0.00, P < 0.05) and doctor-patient communication (ß=-0.33, 95%CI: -0.64-0.02, P < 0.05). CONCLUSIONS: The prevalence of FOC was high in Lianyungang city, Eastern China. FOC is influenced by multiple factors. There is an urgent need to develop interventions to reduce the prevalence of FOC in the third trimester of pregnancy, and to pay attention to pregnant women with risk factors for FOC.

N6-methyladenosine (m6A) Modification in Preeclampsia.

Recently, epitranscriptional modification of N6-methyladenosine (m6A) has received growing attention in the research on the pathogenesis of preeclampsia. Advances in m6A sequencing have revealed the molecular mechanism and importance of m6A modification. In addition, epitranscriptional modification of m6A is closely related to the metabolic processes of placental tissues and cells in preeclampsia. This article reviews the composition, mode of action, and bioinformatics analysis of m6A modification-related proteins, and their biological function in the progression of preeclampsia. The relationship between m6A modification and preeclampsia risk factors, such as diabetes, cardiovascular disease, obesity, and psychological stress, is summarized to provide new ideas for studying PE-targeting molecules.

Downregulated DUXAP8 lncRNA impedes trophoblast cell proliferation and migration by epigenetically upregulating TFPI2 expression.

BACKGROUND: Preeclampsia (PE), a pregnancy complication characterized by new-onset hypertension and proteinuria during the second trimester, is the leading cause of neonatal and maternal morbidity and mortality. In the etiology of PE, failure of uterine spiral artery remodeling may be related to functioning abnormally of trophoblast cells, leading to the occurrence and progression of PE. Recently, long noncoding RNAs (lncRNAs) have been reported to play critical roles in PE nowadays. This study aimed to investigate the expression and functions of the TFPI2 pathway-related lncRNA DUXAP8. METHODS: DUXAP8 expression in the placenta from pregnancies was examined using qPCR. Then, the in vitro functions of DUXAP8 were investigated through MTT, EdU, colony, transwell, and flow cytometry experiments. The downstream gene expression profiles were assessed using RNA transcriptome sequencing analysis and verified using qPCR and western blot. Furthermore, Immunoprecipitation (RIP), chromatin immunoprecipitation (CHIP) and fluorescence in situ hybridization (FISH) were used to detect the interaction between lncDUXAP8/EZH2/TFPI2. RESULTS: The expression of lncRNA DUXAP8 in placenta of patients with eclampsia was significantly decreased. After knockout of DUXAP8, the proliferation and migration of trophoblasts were significantly decreased, and the percentage of apoptosis was increased. Flow cytometry showed that low expression of DUXAP8 increased the accumulation of cells in G2/M phase, while overexpression of DUXAP8 had the opposite effect. We also proved that DUXAP8 epigenetically inhibited TFPI2 expression by recruiting EZH2 and mediating H3K27me3 modification. CONCLUSION: Together, these resulting data clarify that aberrant expression of DUXAP8 is involved in the potential PE development and progress. Unraveling the role of DUXAP8 will provide novel insights into the pathogenesis of PE.

Engineered Escherichia coli as a Controlled-Release Biocarrier for Electrochemical Immunoassay.

Micro/nanocarriers hold great potential in bioanalysis for molecular recognition and signal amplification but are frequently hampered by harsh synthesis conditions and time-consuming labeling processes. Herein, we demonstrate that Escherichia coli (Ec) can be engineered as an efficient biocarrier for electrochemical immunoassay, which can load ultrahigh amounts of redox indicators and simultaneously be decorated with detection antibodies via a facile polydopamine (PDA)-mediated coating approach. Compared with conventional carrier materials, the entire preparation of the Ec biocarrier is simple, highly sustainable, and reproducible. Moreover, immune recognition and electrochemical transduction are performed independently, which eliminates the accumulation of biological interference on the electrode and simplifies electrode fabrication. Using human epidermal growth factor receptor 2 (HER2) as the model target, the proposed immunosensor exhibits excellent analytical performance with a low detection limit of 35 pg/mL. The successful design and deployment of Ec biocarrier may provide new guidance for developing biohybrids in biosensing applications.

Engineering m6A demethylation-activated DNAzyme for visually and sensitively sensing fat mass and obesity-associated protein.

Fat mass and obesity-associated protein (FTO) regulating the N6-methyladenine (m6A, the most pervasive epigenetic modification) levels within the nucleus has been identified as a potential biomarker for cancer diagnosis and prognosis. However, current methods for FTO detection are complicated or/and not sensitive enough for practical application. Herein, we propose a colorimetric biosensor for detecting FTO based on a delicate design of m6A demethylation-activated DNAzyme. Specifically, an m6A-blocked DNAzyme is constructed as a switch of the biosensor that can be turned on by target FTO. The decreased thermal stability resulting from substrate cleavage leads to a DNAzyme recycling to produce multiple primers. Then the rolling circle amplification (RCA) reactions can be initiated to generate G-quadruplex-DNAzymes catalyzing 2,2-azino-bis-(3-ethylben-zthiazoline-6-sulfonic acid (ABTS) oxidation which can be readily observed by the naked eye. Quantitative detection can also be achieved with a limit of detection (LOD) down to 69.9 fM, exhibiting higher sensitivity than previous reports. Therefore, this biosensor opens a simple and sensitive way to achieve visual assay of FTO via triple signal amplification. In addition, our biosensor has been successfully applied to FTO detection in clinical samples, which shows great potential in clinical molecular diagnostics.

IGF2BP2 enhances LincRNA01116 stability via m6 A: A potential biomarker and therapeutic target for patients with pre-eclampsia.

Pre-eclampsia (PE) is a serious complication in pregnant women characterized by failure of placental remodeling and is one of the primary causes of changes in the placental structure and function. The aberrant expression of long noncoding RNA is associated with the occurrence and progression of PE. This study found that linc01116 expression was significantly downregulated in PE patients and was related to poor uterine spiral artery remodeling. Knockdown of linc01116 remarkably decreased the angiogenesis of trophoblast cells in vitro and in vivo. Mechanistically, IGF2BP2 regulated linc01116 RNA stability via m6 A methylation. Bioinformatics and other experiments further revealed that linc01116 upregulates AAMP expression by adsorbing miR-210-3p in trophoblast cells. In conclusion, this study revealed the critical role of linc01116 in regulating trophoblast angiogenesis. Furthermore, the study provides new clues for detecting placental pathology in PE.

Functionalization of Covalent Organic Frameworks with Peptides by Polymer-Assisted Surface Modification and the Application for Protein Detection.

Although covalent organic frameworks (COFs) have received extensive attention for biomedical research due to their unique properties, their application is still hindered by the challenges of incorporating COFs with functional biomolecules. Since peptides have shown advantages in biomedical applications, herein, we propose the functionalization of COFs with peptides by a polymer-assisted surface modification strategy. Furthermore, a method based on the peptide-functionalized COFs for protein detection has also been developed to demonstrate their application potential. With the help of the polymers, peptides and horseradish peroxidase are attached onto COFs with a high surface density, and the developed method has achieved simple and sensitive detection of the secreted protein acidic and rich in cysteine. We speculate that the facile method proposed in this work to prepare peptide-functionalized COFs can not only benefit protein detection but also promote more biomedical applications of COFs.

Spiral Suture of the Lower Uterine Segment with Temporary Aortic Balloon Occlusion in Morbidly Adherent Placenta Previa Cases.

Purpose: We aimed to investigate the combined effect of spiral suture of the lower uterine segment with intraoperative aortic balloon occlusion in morbidly adherent placenta previa cases. Patient and Methods: This retrospective, single-center study involved patients from 2017 to 2020. The study considered 68 cases of morbidly adherent placenta previa cases from medical records retrospectively with age ranging from 23 to 42 years. Bilateral uterine artery embolization was performed, to control excessive bleeding. Perioperative blood loss, hysterectomy rate, amount of blood transfusion, balloon occlusion time, fetal and maternal radiation dose, and postpartum complications were assessed. Results: A total of 68 patients underwent surgery. Hysterectomy was performed in three patients and uterine artery embolization in 21 patients. Of 53 patients who required blood transfusions, the amount of packed red blood cells given was 800 mL and the amount of plasma given was 400 mL. Median abdominal aortic balloon occlusion time was 17 minutes. Fetal and maternal radiation doses were 5 mGy and 12 mGy, respectively. One patient experienced surgery-related complications, a bladder injury. No major catheterization-related and postpartum complications were observed. Conclusion: Fertility-sparing surgery for women with morbidly adherent placenta could include abdominal aortic balloon occlusion and spiral suture of lower uterine segment.

A novel regulated network mediated by downregulation HIF1A-AS2 lncRNA impairs placental angiogenesis by promoting ANGPTL4 expression in preeclampsia.

Preeclampsia (PE) is the predominant medical condition leading to maternal and fetal mortality, and the lack of effective treatment increases its risk to the public health. Among the numerous predisposing factors, the ineffectual remodeling of the uterine spiral arteries, which can induce abnormal placental angiogenesis, has been focused to solve the pathogenesis of PE. According to the preceding research results, abnormal expression of long non-coding RNAs (lncRNA)s could be associated with the pathological changes inducing PE. To be more specific, lncRNA HIF1A-AS2 was proposed for its potential to participate in the molecular mechanisms underlying PE. In vitro, in trophoblast cell lines HTR-8/SVneo and human umbilical vein endothelial cells HUVECs, HIF1A-AS2 knockdown inhibited cell proliferation, migration and tube formation. Mechanistically, transcription factor FOXP1 could regulate the expression of HIF1A-AS2. Moreover, a series of assays, including RNA pull down and mass spectrometry, RNA immunoprecipitation and chromatin immunoprecipitation assay, revealed that HIF1A-AS2 interacted with Lamin A/C (LMNA) to inhibit ANGPTL4 expression in trophoblast cells, thus further participating in the progression of PE. Taken together, these findings suggested that further analysis on HIF1A-AS2 could contribute to the development of prospective therapeutic strategy for PE.

Identification of a novel heterozygous missense TP63 variant in a Chinese pedigree with split-hand/foot malformation.

BACKGROUND: Tumor protein p63 is an important transcription factor regulating epithelial morphogenesis. Variants associated with the TP63 gene are known to cause multiple disorders. In this study, we determined the genetic cause of split-hand/foot malformation in a Chinese pedigree. METHODS: For this study, we have recruited a Chinese family and collected samples from affected and normal individuals of the family (three affected and two normal). Whole exome sequencing was performed to detect the underlying genetic defect in this family. The potential variant was validated using the Sanger sequencing approach. RESULTS: Using whole-exome and Sanger sequencing, we identified a novel heterozygous pathogenic missense variant in TP63 (NM_003722.5: c.921G > T; p.Met307Ile). This variant resulted in the substitution of methionine with isoleucine. Structural analysis suggested a resulting change in the structure of a key functional domain of the p63 protein. CONCLUSION: This novel missense variant expands the TP63 variant spectrum and provides a basis for genetic counseling and prenatal diagnosis of families with split-hand/foot malformation or other TP63-related diseases.