Prospective Investigation of Optical Genome Mapping for Prenatal Genetic Diagnosis.

BACKGROUND: Optical genome mapping (OGM) is a novel assay for detecting structural variants (SVs) and has been retrospectively evaluated for its performance. However, its prospective evaluation in prenatal diagnosis remains unreported. This study aimed to prospectively assess the technical concordance of OGM with standard of care (SOC) testing in prenatal diagnosis. METHODS: A prospective cohort of 204 pregnant women was enrolled in this study. Amniotic fluid samples from these women were subjected to OGM and SOC testing, which included chromosomal microarray analysis (CMA) and karyotyping (KT) in parallel. The diagnostic yield of OGM was evaluated, and the technical concordance between OGM and SOC testing was assessed. RESULTS: OGM successfully analyzed 204 cultured amniocyte samples, even with a cell count as low as 0.24 million. In total, 60 reportable SVs were identified through combined OGM and SOC testing, with 22 SVs detected by all 3 techniques. The diagnostic yield for OGM, CMA, and KT was 25% (51/204), 22.06% (45/204), and 18.14% (37/204), respectively. The highest diagnostic yield (29.41%, 60/204) was achieved when OGM and KT were used together. OGM demonstrated a concordance of 95.56% with CMA and 75.68% with KT in this cohort study. CONCLUSIONS: Our findings suggest that OGM can be effectively applied in prenatal diagnosis using cultured amniocytes and exhibits high concordance with SOC testing. The combined use of OGM and KT appears to yield the most promising diagnostic outcomes.

Common carotid artery thrombosis and malignant middle cerebral artery infarction following ovarian hyperstimulation syndrome: A case report.

BACKGROUND: Arterial thrombosis is a serious and rare complication of ovarian hyperstimulation syndrome (OHSS). Herein, we describe a case of OHSS complicated by common carotid artery thrombosis and malignant middle cerebral artery infarction after egg retrieval and before embryo transfer. CASE SUMMARY: A 32-year-old female with a family history of thrombosis who was undergoing in vitro fertilization due to unexplained infertility, was admitted due to abdominal distension for 3 d and coma for 2 h. She received egg retrieval 7 d ago and embryo transfer had not yet been performed. Blood biochemical analysis showed estrogen of 15781 pmol/L. Gynecological examination showed palpable masses on both sides of the adnexal areas. Ultrasound observed enlarged ovaries and abdominal ascites. Imaging examination of the head and neck revealed fresh malignant middle cerebral artery infarction in the left side of brain and internal carotid artery as well as occlusion in the left carotid artery, internal carotid artery, and middle cerebral artery. The patient was finally diagnosed with severe OHSS, complicated by common carotid artery thrombosis and malignant middle cerebral artery infarction. Liquid replacement, anticoagulation, vascular endothelium protection, brain protection and decompressive craniectomy were carried out. Rehabilitation training was then performed for 6 mo. At present, she has poor speaking ability and decreased muscle strength on the right side. CONCLUSION: There is a risk of thrombosis during any period of OHSS. During in vitro assisted reproduction, for cases with a family history of thrombosis, hyperlipidemia and other high-risk factors, serum lipid levels should be controlled as soon as possible to improve metabolic dysfunction. When thrombosis occurs, timely and effective treatment should be performed to improve the prognosis.

MicroRNA-214-3p Targeting Ctnnb1 Promotes 3T3-L1 Preadipocyte Differentiation by Interfering with the Wnt/ß-Catenin Signaling Pathway.

Differentiation from preadipocytes into mature adipocytes is a complex biological process in which miRNAs play an important role. Previous studies showed that miR-214-3p facilitates adipocyte differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) in vitro. The detailed function and molecular mechanism of miR-214-3p in adipocyte development is unclear. In this study, the 3T3-L1 cell line was used to analyze the function of miR-214-3p in vitro. Using 5-Ethynyl-2'-deoxyuridine (EdU) staining and the CCK-8 assay, we observed that transfection with the miR-214-3p agomir visibly promoted proliferation of 3T3-L1 preadipocytes by up-regulating the expression of cell cycle-related genes. Interestingly, overexpression of miR-214-3p promoted 3T3-L1 preadipocyte differentiation and up-regulated the expression of key genes for lipogenesis: PPARγ, FABP4, and Adiponectin. Conversely, inhibition of miR-214-3p repressed 3T3-L1 preadipocyte proliferation and differentiation, and down-regulated the expression of cell cycle-related genes and adipogenic markers. Furthermore, we proved that miR-214-3p regulates 3T3-L1 preadipocyte differentiation by directly targeting the 3'-untranslated regions (3'UTR) of Ctnnb1, which is an important transcriptional regulatory factor of the Wnt/ß-Catenin pathway. Taken together, the data indicate that miR-214-3p may positively regulate preadipocyte proliferation and enhance differentiation through the Wnt/ß-Catenin signaling pathway.

Maternal circulating levels of transforming growth factor-ß superfamily and its soluble receptors in hypertensive disorders of pregnancy.

OBJECTIVE: To assess circulating levels of transforming growth factor (TGF)-ß superfamily members and their soluble receptors in hypertensive disorders of pregnancy, and to investigate associations with clinical manifestations. METHODS: A retrospective study was conducted using data for women admitted to a center in China for delivery between May 2011 and April 2013. Women with severe pre-eclampsia, mild pre-eclampsia, and gestational hypertension were included, along with a control group. Serum levels of activin A, inhibin A, TGF-ß1, soluble endoglin (sEng), and soluble betaglycan (sBG) were measured. RESULTS: Women with severe pre-eclampsia (n = 17) had higher mean levels of activin A (23.5±2.1 µg/L), inhibin A (1.7±0.2 µg/L), sEng (32.1±3.2 µg/L), and sBG (84.1±9.4 µg/L) than did normotensive controls (n = 18), women with gestational hypertension (n = 15), and those with mild pre-eclampsia (n = 14; all P<0.05). Women with early-onset pre-eclampsia (n = 13) had higher levels of these serum markers than did preterm normotensive controls (n = 8; all P<0.001). Women with severe or early-onset pre-eclampsia had the lowest TGF-ß1 levels. Activin A, inhibin A, sEng, and sBG levels were positively correlated with mean arterial pressure and proteinuria (all P<0.01). CONCLUSION: Pre-eclampsia is associated with an imbalance of members of the TGF-ß superfamily and their soluble receptors, which might contribute to the development of pre-eclampsia and help to predict onset and severity.

MicroRNA-126 is down-regulated in human esophageal squamous cell carcinoma and inhibits the proliferation and migration in EC109 cell via PI3K/AKT signaling pathway.

MicroRNA-126 (miR-126) was found down-regulated in different types of cancer including esophageal squamous cell carcinoma (ESCC). However, the onco-genetic role of miR-126 in ESCC still remains unknown. In the present study, we found the relative expression of miR-126 in ESCC was significant decreased in ESCC tissues compared to adjacent normal tissues. Overexpression of miR-126 in EC109 cells resulted in significant decrease in cell proliferation, colon formation and migration. PI3K regulatory subunit p85 beta (PIK3R2), a member of PI3K/AKT signaling pathway was found upregulated in ESCC tissues and there is a negative relation between expression of PIK3R2 and miR-126. Restoration of miR-126 in EC109 cells induced a reduction in PIK3R2 protein levels, accompanied with a substantial reduction in phosphorylated AKT levels in EC109 cells, suggesting impairment in PI3K/AKT signaling pathway. The luciferase reporter assay confirmed that PIK3R2 was a direct target of miR-126. Furthermore, we also indicated overexpression of miR-126 suppresses G2/M transition in EC109 cells. Taken together, our study suggests that miR-126 functions as a potential tumor suppressor in ESCC progression via regulating PI3K/AKT signaling pathway partly by targeting PIK3R2, and targeting of miR-126 may provide a novel strategy for the diagnosis and treatment of ESCC.