Prenatal detection of pure proximal 6q14.1 microduplication encompassing LCA5 gene: A variant of likely benign.

ABSTRACT: Trisomy 6q is a recognizable syndrome which exhibits psychomotor/growth retardation, developmental/intellectual disabilities, feeding difficulties, facial dysmorphism, hearing loss, brain and heart malformations. The purpose of this study was to delineate the prenatal features of proximal 6q14.1 duplication in fetal period, which was rarely reported in clinic. Eight pregnant women who opted for amniocentesis due to the fetal ultrasound abnormalities, maternal serum screening or other indications for prenatal diagnosis between 2019 and 2020. Chromosomal microarray analysis and G-banding analysis were offered after informed consents were obtained. Cytogenetic prenatal investigation showed all fetuses presented normal karyotypes except case 4 exhibiting a balanced chromosomal translocation 46,XX,t (4;8)(p16;q24). The chromosomal microarray analysis detected 0.211-0.242 Mb duplications of 6q14.1 (chr6: 80109532-80351666, hg19) in all 8 cases, encompassing the morbid gene LCA5 in common. Seven pregnant women (P1-P7) continued their pregnancies and delivered healthy infants at term while the parents of case 8 opted for termination of pregnancy for severe abnormal ultrasound findings. Overall, all neonates were in a good healthy condition with no evident anomalies, ranging from 2 m to 16 m. It is proposed that 6q14.1 duplication involving LCA5 gene detected in our study might be variants of likely benign. However, further large-scale studies should be gathered to assess its pathogenicity. To our knowledge, our study is the first report focusing on prenatally detected proximal 6q14.1 duplication, accompanied by detailed clinic phenotypes. Diverse ultrasound findings were observed in these cases, ranging from normal to abnormal. More evidence should be gathered to interpret the prenatal genotype-phenotype correlation of 6q14.1 duplication. For these cases with 6q14.1 microduplication, long term follow up should be carried out in case abnormal clinical symptoms or developmental-behavioral disorders emerge.

Olaparib and Doxorubicin Co-Loaded Polypeptide Nanogel for Enhanced Breast Cancer Therapy.

Although great progress has been made in improving the efficacy of cancer treatment through combination treatment using drug agents, there are still challenges in improving the efficiency of drug delivery. In this study, olaparib and doxorubicin were co-loaded on disulfide bond cross-linked polypeptide nanogels for the treatment of breast cancer in mouse models. Under stimulation of a high glutathione environment in cancer cells, the drug is quickly released from the nanogel to target cancer cells. In addition, compared with free drugs and single-drug-loaded nanogels, dual-drug- co-loaded nanogels exhibit the best anti-cancer effect and demonstrated excellent biological safety. Therefore, the co-delivery of olaparib and doxorubicin through polypeptide nanogels presents good prospects for application as anti-cancer treatment.

ICSI outcomes of fresh or cryopreserved spermatozoa from micro-TESE in patients with nonobstructive azoospermia: CONSORT.

ABSTRACT: The aim of this study was to evaluate intracytoplasmic sperm injection (ICSI) outcomes of fresh and cryopreserved sperm via microdissection testicular sperm extraction (micro-TESE) in patients with nonobstructive azoospermia (NOA).From March 2016 to February 2020, a total of 244 men with NOA underwent micro-TESE at the Center for Reproductive Medicine, First Hospital of Jilin University, P. R. China. These cases included 40 patients who underwent 40 ICSI cycles with fresh spermatozoa from micro-TESE (Group A) and 30 patients who underwent 30 ICSI cycles with cryopreserved spermatozoa from micro-TESE (Group B). The characteristics, embryonic development, and ICSI outcomes of patients were compared between groups A and B.Our sperm retrieval rate (SRR) by micro-TESE in patients with NOA was 35.25%. No statistical differences in the patient characteristics and fertilization or quality embryo rates were observed between Groups A and B. Higher miscarriage rates and lower live births were observed in Group B than in Group A (both P < .05).Fresh testicular spermatozoa seem to produce better ICSI outcomes than cryopreserved testicular spermatozoa from patients with NOA in the micro-TESE-ICSI cycle.

Pristimerin Suppresses Trophoblast Cell Epithelial-Mesenchymal Transition via miR-542-5p/EGFR Axis.

BACKGROUND: Ectopic pregnancy (EP) is an ectopic embryo implantation occurred outside the uterine cavity. Nowadays, more attention have garnered in fast and effective treatment with less side effects. Pristimerin is known as the clinical application for anti-cancer, and the effect on EP therapy is still unclear. MATERIALS AND METHODS: Trophoblast cell line HTR-8/SVneo was used; then, we performed cell counting kit-8 assay, wound healing assay, flow cytometry and real-time polymerase chain reaction analysis (RT-PCR) to detect the cell viability, migration ability, apoptosis and epithelial-mesenchymal transition (EMT) under pristimerin treatment. In addition, public bioinformatic database was used to discover the connection between molecular and genes. Finally, we used miRNA transfection and RT-PCR techniques to determine the underlying molecular mechanism. RESULTS: We revealed that pristimerin inhibited trophoblast cells proliferation, migration and EMT, while induced trophoblast cell apoptosis. Furthermore, expression of miR-542-5p, AGO2 and EGFR was suppressed in HTR-8/SVneo cells post pristimerin treatment, and miR-542-5p silence showed the same effect. Combing pristimerin treatment and miR-542-5p silence showed a synergistic action. CONCLUSION: Pristimerin could be an effective treatment to block embryo implantation by miR-542-5p and EGFR down-regulation.

A novel FGFR2 (S137W) mutation resulting in Apert syndrome: A case report.

RATIONALE: Apert syndrome (AS) is an autosomal dominant inheritance pattern of the most severe craniosynostosis syndrome. AS is characterized by synostosis of cranial sutures and acrocephaly, including brachycephaly, midfacial hypoplasia, and syndactyly of the hands and feet. Patients with AS often present with craniosynostosis, severe syndactyly, and skin, skeletal, brain, and visceral abnormalities. PATIENT CONCERNS: A pregnant Chinese woman presented with a fetus at 23 + 5 weeks of gestation with suspected AS in a prenatal ultrasound examination. Following ultrasound, the pregnancy underwent spontaneous abortion. Gene sequencing was performed on the back skin of the dead fetus. DIAGNOSIS: The diagnosis of AS was confirmed on the basis of clinical manifestations of the fetus, and a de novo mutation in the fibroblast growth factor receptor 2 (FGFR2) gene was identified. INTERVENTIONS: The couple finally chose to terminate the pregnancy based on the ultrasonic malformations and the risk of the parents having a neonate with AS in the future is small. However, any future pregnancy must be assessed by prenatal diagnosis. OUTCOMES: The dead fetus presented with bilateral skull deformation. Additionally, there were bilateral changes to the temporal bone caused by inwards movement leading to concave morphology, a "clover" sign, and syndactyly from the index finger/second toe to the little finger/little toe. AS was diagnosed by genetic testing, which showed a p.S137W (c.410C>G, chr10:123279677) mutation in the FGFR2 gene. LESSONS: Clinicians should be aware that there are a variety of ultrasound findings for AS. Therefore, genetic testing should be used when appropriate to confirm diagnosis of AS.

Essential thrombocytosis with recurrent spontaneous abortion in the mid trimester: A case report.

RATIONALE: Essential thrombocytosis (ET) is a myeloproliferative neoplasm characterized by clonal proliferation of the megakaryocytic lineage within the bone marrow and phenotypically by an elevated platelet count in peripheral blood. Common vascular complications include thrombosis, microvascular disturbances, and hemorrhage. ET with recurrent spontaneous abortion as the primary symptom is rare. PATIENT CONCERNS: A 30-year-old pregnant woman (gestational age: 8 weeks) with a history of recurrent spontaneous abortion in the mid trimester was admitted to our hospital for further management. DIAGNOSIS: The diagnosis of ET was made based on the platelet count, bone marrow biopsy, and molecular biology testing. INTERVENTIONS: The patient was treated with interferon, heparin, and aspirin. OUTCOMES: The infant was delivered by cesarean section without complication at 28 weeks gestation due to placental abruption. The child remained healthy with no developmental abnormalities during follow-up for 2 years. LESSONS: Recurrent spontaneous abortion in the mid trimester might be associated with ET. Thus, a detailed investigation including blood routine examination to identify an abnormal platelet count is warranted for pregnant patients with such a history in order to facilitate timely treatment.

Exploring prognostic genes in ovarian cancer stage-related coexpression network modules.

Identification of meaningful cluster modules of differential genes or representative biomarkers related to the stages of ovarian cancer (OC) is pivotal, which may help to detect mechanisms of OC progression and evaluate OC patients' prognosis.We downloaded gene expression data and the corresponding clinical information of OC patients from The Cancer Genome Atlas (TCGA) database, which included 379 ovarian cancer patients. Differentially expressed genes (DEGs) of OC patients between stages were picked out using R. There were 731 differential genes between ovarian cancer stage II and stage III (DEGs II-III) and 563 differential genes between ovarian cancer stage III and stage IV (DEGs III-IV), then we performed GO analysis and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analysis using Database for Annotation, Visualization and Integrated Discovery (DAVID). Moreover, CytoHubba was used to detect the top 20 hub genes in DEGs II-III and DEGs III-IV, followed Cytoscape with search tool for the retrieval of interacting genes (STRING) and MCODE plug-in was utilized to construct protein-protein interaction (PPI) modules of these genes. Three important coexpression modules of DEGs II-III and 3 more meaningful modules of DEGs III-IV were detected from PPI network using molecular complex detection (MCODE) tool. In addition, 5 hub genes in these stage-related DEGs modules with worse overall survival were selected, including COL3A1, COL1A1, COL1A2, KRAS, NRAS. This bioinformatics analysis demonstrated that stage-related prognostic DEGs, such as COL3A1, COL1A1, COL1A2, KRAS, and NRAS might play an unfavorable role in the development as well as metastasis of ovarian cancer. Furthermore, they need to be experimentally verified as a new biomarker to predict OC patient prognosis.

Intracytoplasmic sperm injection outcome of ejaculated spermatozoa from a man with mosaic Klinefelter's Syndrome: case report and literature review.

Objective To report a case of abortion after intracytoplasmic sperm injection (ICSI) with ejaculated spermatozoa obtained from a man with mosaic Klinefelter's syndrome. Methods Sperm nuclei from the patient were analyzed by fluorescence in situ hybridization, and the disomy frequencies for chromosome 18 and the sex chromosomes were determined. A literature review of the ICSI outcome of ejaculated sperm in patients with Klinefelter's syndrome was also performed. Results A total of 108 spermatozoa nuclei were analyzed. Of these, 102 sperm cells were normal with an X18 (55.56%) or Y18 (38.89%) chromosome pattern. Three cells with XX18 (2.78%) and three cells with YY18 (2.78%) signals were detected. The fetus stopped developing in the eighth week. The karyotype determined by an analysis of the abortive tissue was 46, XY. The literature review identified a total of 12 patients who were analyzed in 11 reports. The fertilization rate was 80.9%, and the live birth rate per transfer was 71.4%. Conclusions ICSI with ejaculated spermatozoa from men with Klinefelter's syndrome can lead to pregnancy, for which the risk of transmission of chromosomal aneuploidy is low.

Effect of chromosomal polymorphisms of different genders on fertilization rate of fresh IVF-ICSI embryo transfer cycles.

To explore whether chromosomal polymorphisms of different genders affect outcomes of fresh IVF and intracytoplasmic sperm injection (ICSI) embryo transfer cycles differently, 37 couples with chromosomal polymorphisms were identified out of 614 infertile couples undergoing IVF-ICSI treatments. Group 1 included 20 couples in which only the male carried chromosomal polymorphisms; group 2 included 17 couples with female carriers only; group 3 included 19 infertile couples with normal karyotypes randomly selected as controls. A significantly lower fertilization rate was found in group 1 compared with groups 2 and 3 (56.68% in Group 1, 78.02% in group 2 and 71.74% in group 3; group 1 versus group 2, P < 0.001; group 1 versus group 3, P = 0.001; respectively). When stratified according to fertilization method, the fertilization rate in IVF cycles of group 1 was significantly lower than group 3 (50.00% in Group 1, 73.89% in Group 3, P < 0.001). Fertilization rates in ICSI cycles between groups 1 and 3 were not significantly different. This study suggests that male chromosomal polymorphisms adversely influence fertilization rates of IVF cycles. The use of ICSI may improve the success of infertility treatment by increasing the fertilization rate for men with chromosomal polymorphisms.