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Robust cost efficacy of a novel,validated screening test at 12–20 Weeks gestation for the prediction of preterm birth(PTB)at or before 32 Weeks in singletons

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gynecology and obstetrics Clinical Medicine 2021年第3期1卷 107-111页

作者： Robert H.Lee Carl P.Weiner departments of Population Health University of Kansas School of MedicineUSA departments of obstetrics and gynecology and molecular and integrative physiology University of Kansas School of MedicineKansas CityKS66160USA

Objective:Preterm birth(PTB)at or before 32 weeks complicates up to 2%of United States(US)births and accounts for 80%of perinatal expenditures in the first year of *** screening tests for PTB performed from 12 weeks to 19 weeks 5 days have receiver operated area under the curve(AUC)indices of<80%and at most<70%.We evaluated FutureBIRTH™,a unique maternal screening test comprised of plasma cell-free RNA for the prediction of PTB≦32 weeks due to spontaneous labor(sPTB)with or without preterm premature rupture of the membranes(PPROM)or early-onset pre-eclampsia before 34 weeks(EOP).FutureBIRTH™is supported by multiple validation studies derived from 12 weeks to 19 weeks 5 days gestation achieving AUCs of 84.2%for sPTB and 94.1%for ***:Using the US rates for EOP(0.5%)and sPTB≦32 weeks(1.8%)and adjusting the US pregnancy/neonatal medical costs to US dollars(2017 value),we calculated the cost per 100,000 singletons with or without universal FutureBIRTH™testing before 19 weeks and 6 days using three detection rates and assuming screenpositive women would be treated with and respond to aspirin(assumed 80%efficacy for EOP)and vaginal progesterone(assumed 38%efficacy for sPTB).We also assessed test performance at disease incidence rates below that of the US(down to 0.46%).For considering screening costs,we assumed test costs of$750,and treatment costs of$1000 for patients over 20 weeks gestational ***:The identification and treatment of‘at-risk’pregnancies by FutureBIRTH™with existing therapies would reduce direct healthcare costs by up to$95 million per 100,000 *** projected savings were robust and achievable at each FutureBIRTH™price despite the conservative costs,efficacy,and detection rate *** incidence of PTB≦32 weeks would decline by 40%–50%with a test cost of$750 and an 80%detection ***:The accurate risk assessment provided by universal FutureBIRTH™screening coupled with existing preventative treatments could lea

关键词： Pregnancy Preterm birth Transcriptome Plasma RNA Precision medicine

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Epigenetic marks in zebrafish sperm： insights into chromatin compaction, maintenance of pluripotency, and the role of the paternal genome after fertilization

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Asian Journal of Andrology 2011年第4期13卷 620-621页

作者： Douglas T Carrell Andrology and IVF Laboratories Departments of Surgery （Urology） Obstetrics and Gynecology and Physiology University of Utah School of Medicine Salt Lake City UT 84108 USA

Human sperm chromatin, and the sperm of most mammals, undergoes extensive remodeling during spermiogenesis during which 85%-95% of the histones are removed and replaced with protamines. The replacement of most histones with protamines facilitates a tighter packaging of the chromatin that is necessary for normal sperm function, and may help protect sperm DNA from damage during transport.

关键词： Epigenetic fertilization

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Antisense Oligodeoxynucleotide Inhibits Expression of Re-com binantPorcine Follicle-Stim ulating Horm one Receptor

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Journal of Huazhong University of Science and Technology(Medical Sciences) 1999年第3期19卷 175-180页

作者： ZHU Changhong 1, Mark D. Nixon 2, WANG Yifang 1, Andrew R. LaBarbera 3 1 Center of Reproductive Medicine, Tongji Hospital, Tongji Medical University, Wuhan 430030 2 Department of obstetrics and gynecology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267 0526 3 Department of molecular and Cellular physiology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267 0526 Center of Reproductive Medicine Tongji Hospital Tongji Medical University Wuhan Department of obstetrics and gynecology University of Cincinnati College of Medicine Cincinnati Department of molecular and Cellular physiology University of Cincinnati College of Medicine Cincinnati

To assess the role of follicle stimulating hormone receptor(FSHR) gene expression in regulating expression of FSHR protein in the plasma membrane, the effects of a porcine FSHR cDNA antisense oligodeoxynucleotide (ODN) on FSHR mRNA levels and 125 I FSH binding were determined in Chinese hamster ovary cells expression recombinant porcine FSHR (pFSHR CHO cells). An 18 mer phosphorothioate endcapped antisense ODN that corresponded to the region surrounding the translation initiation codon of the porcine FSHR cDNA was synthesized. An 18 mer nonsense sequence of identical nucleotide composition, which had little homology to known DNA sequences, was synthesized for use as a control. pFSHR CHO cells were cultured in 24 well plates (10 5 cells/well) in the absence or presence of 1 20 μmol/L antisense or nonsense ODN for 24 h and then assayed for porcine FSHR mRNA, using quantitative reverse transcription and competitive polymerase chain reaction, and for 125 I FSH binding activity. Treatment with 10 μmol/L antisense ODN caused a paradoxical increase in porcine FSHR mRNA from 0.89±0.06 to 1.64±0.08 ng/mg total RNA ( P <0.05). Transfection with lipofectamine and 0.33 μmol/L antisense ODN caused an increase in porcine mRNA from 0.95±0.08 to 1.53±0.07 ng/mg total RAN. This was probably due to upregulation of mRNA synthesis resulting from inhibition of porcine FSHR protein translation. The nonsense ODN had no effect on porcine FSHR mRNA. Antisense, but not nonsense, ODN (10 μmol/L) inhibited membrane binding of 125 I FSH by 13.6± 0.8 % ( P <0.05) in 24 h. Treatment of cells with antisense ODN (10 μmol/L) for 48 h resulted in a 76±1.5 % ( P <0.05) inhibition of 125 I FSH binding. In contrast, transfection with lipofectamine and 0.33 μmol/L antisense ODN at 0 h caused a 76.1±1.3 % ( P <0.05) reduction in binding within 24 h. Binding had returned to 52.3±2.3 % ( P < 0.05) of normal by 48 h. These results indicate

关键词： follicle stimulating hormone antisense oligodeoxynucleotide folliculogenesis mRNA spermatogenesis

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Stretch-induced human myometrial cytokines enhance immune cell recruitment via endothelial activation

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Cellular & molecular Immunology 2015年第2期12卷 231-242页

作者： Yu-Hui Lee Lunenfeld-Tanenbaum Research Institute Mount Sinai Hospital Toronto Canada Department of physiology University of Toronto Toronto Canada Department of obstetrics & gynecology University of Toronto Toronto Canada

Spontaneous term labour is associated with amplified inflammatory events in the myometrium including cytokine production and leukocyte infiltration; however, potential mechanisms regulating such events are not fully understood. We hypothesized that mechanical stretch of the uterine wall by the growing fetus facilitates peripheral leukocyte extravasation into the term myometrium through the release of various cytokines by uterine myocytes. Human myometrial cells （hTERT-HM） were subjected to static mechanical stretch; stretch-conditioned media was collected and analysed using 48-plex Luminex assay and ELISA. Effect of stretch-conditioned media on cell adhesion molecule expression of human uterine microvascular endothelial cells （UtMVEC-Myo） was detected by quantitative polymerase chain reaction （qPCR） and flow cytometry; functional assays testing leukocyte-endothelial interactions： adhesion of leukocytes to endothelial cells and transendothelial migration of calcein-labelled primary human neutrophils as well as migration of THP-1 monocytic cells were assessed by fluorometry. The current in vitrostudy demonstrated that mechanical stretch （i） directly induces secretion of multiple cytokines and chemokines by hTERT-HM cells （IL-6, CXCL8, CXCL1, migration inhibitory factor （MIF）, VEGF, G-CSF, IL-12p70, bFGF and platelet-derived growth factor subunit B （PDGF-bb）, P〈0.05）; stretch-induced cytokines （ii） enhance leukocyte adhesion to the endothelium of the surrounding uterine microvasculature by （iii） inducing the expression of endothelial cell adhesion molecules and （iv） directing the transendothelial migration of peripheral leukocytes. （vi） Chemokine-neutralizing antibodies and broad-spectrum chemokine inhibitor block leukocyte migration. Our data provide a proof of mechanical regulation for leukocyte recruitment from the uterine blood vessels to the myometrium, suggesting a putative mechanism for the leukocyte infiltrate into the uterus during labour and postpartum involu

关键词： endothelium labour leukocyte infiltration stretch uterus

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The expression of insulin-like growth factor-Ⅰ mRNA and polypeptide in rat osteoblasts with exposure to parathyroid hormone

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Chinese Medical Journal 2003年第12期116卷 1916-1922页

作者：张克勤陈家伟王美莲汪承亚李光富郑肇熙赵人铮 departments of Endocrinology The First Affiliated Hospital of Nanjing Medical University departments of Endocrinology obstetrics & gynecology The First Affiliated Hospital of Nanjing Medical University Institute of molecular Biology and Institute of Applied Toxicology Nanjing Medical University departments of Endocrinology and Pathology The First Affiliated Hospital of Nanjing Medical University Institute of molecular Biology Nanjing Medical University

Objective To investigate the insulin-like growth factor-Ⅰ (IGF-Ⅰ) gene and polypeptide expression in cultured rat osteoblast (ROB) and the role of IGF-Ⅰ in mediating the cell-to-cell communication by mimicking the pharmacokinetics of parathyroid hormone (PTH). Methods The ROB was cultured with three kinds of treatment: (1) Control (Ctr), the cells were cultured without PTH during the first 6 hours and the subsequent 42 hours in a 48-hour cycle; (2) Intermittent exposure to PTH (Itm), the cells were cultured with PTH during the first 6 hours, but without PTH in the subsequent 42 hours; and (3) Continuous exposure to PTH (Ctu), the cells were cultured with PTH during the first 6 hours and the subsequent 42 hours. Results The bone-forming activities of ROB were increased in Itm and inhibited in Ctu. The IGF-Ⅰ mRNA content in Itm cells was elevated only during the first 6 hours and that in Ctu cells was elevated at any time during an incubation cycle. The free IGF-Ⅰ concentration in the medium of Itm cells was generally higher and that of the Ctu cells was generally lower compared with those of the Ctr cells. The IGF-Ⅰ antibody significantly reduced the alkaline phosphatase activity within the cells of Ctr and Itm. Conclusions PTH rapidly and constantly stimulates the IGF-Ⅰ gene transcription of osteoblast. There was an obvious discrepancy between the IGF-Ⅰ mRNA content within the osteoblast and the free IGF-Ⅰ level around the osteoblast in either mode of PTH action. The IGF-Ⅰ might be important for osteoblast-osteoblast communication and bone-forming activity, not only in intermittent PTH administration, but also in the physiological functioning of osteoblasts.

关键词： parathyroid hormone osteoporosis osteoblast cytology insulin-like growth factor-Ⅰ

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Re： Is PAWP the ＇real＇ sperm factor？

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Asian Journal of Andrology 2015年第3期17卷 446-449页

作者： Mahmoud Aarabi Peter Sutovsky Richard Oko Department of Human Genetics School of Medicine McGill University Montreal QC Canada Division of Animal Sciences University of Missouri Columbia MO USA departments of obstetrics Gynecology and Women's Health School of Medicine University of Missouri Columbia MO USA Department of Biomedical and molecular Sciences School of Medicine Queen's University Kingston ON Canada

This letter is in response to an article written by Michail Nomikos, Karl Swann and F. Anthony Lai in the Research Highlights section of the Asian Journal of Andrology （AJA）. The article is entitled, ＂Is PAWP the ＇real＇ sperm factor？＂ and was written in response to our article entitled, ＂Sperm-derived WW domain-binding protein, PAWP, elicits calcium oscillations and oocyte activation in human and mouse＂ published recently in FASEB Jol According to the Science Editor of AJA, ＂Research Highlight＂ pieces are brief articles that are meant to report on publications from the primary literature. Along those lines, we were delighted to read an insightful comment on our FASEB article prepared for AJA by Dr. George L Gerton.

关键词： @@

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Expression Compilation of Several Putative Cancer Stem Cell Markers by Primary Ovarian Carcinoma

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Journal of Cancer Therapy 2010年第4期1卷 165-173页

作者： Di Jiabo Yigit Refika G. Figdor Carl Duiveman-de Boer Tjitske Massuger Leon Torensma Ruurd Department of obstetrics and gynecology Nijmegen Centre for Molecular Life Sciences Radboud University Nijmegen Medical Centre Nijmegen the Netherlands departments of Tumor Immunology

Cancer stem cells (CSCs) or tumor initiating cells are rare cells that are able to establish a tumor or metastasis. Identification of those CSCs is, however, cumbersome even in established cell lines. Several cancer stem cell markers were reported to be expressed by ovarian cancer. Those cancer stem cells are gifted with lower vulnerability to irradiation and cytostatic drugs explaining the high incidence of recurrence after treatment. A variety of different cancer stem cell markers were described for epithelial tumors. Also, cancer cell lines were assessed for stem cell markers with no common denominator. The expression of CD24, CD44, CD117, CD133, ABCG2, ALDH was determined for cells from 22 patients. Ovarian cancer cells were collected from ascites. Part of the tumor cells were analyzed immediately and stained for the above mentioned cancer stem cell markers. The remainder of the cells was cultured for several weeks using standard stem cell culture conditions. We observed a large variety in expression of putative stem cell markers for primary tumors. After two weeks of culture spheres were seen in several cultures, indicative for cancer stem cells, though not all patients’ cells were able to form spheres. Our data show for the first time the heterogeneity in marker display in primary tumors. Also for the cultured cells stem cell markers were determined. None of the stem cell markers was expressed by all patients’ cells. No correlation with tumor type was demonstrated. The complexity of expression challenges the isolation of cancer stem

关键词： Ovarian Cancer Cancer Stem Cells Stem cell markers

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Negative biomarker-based male fertility evaluation： sperm phenotypes associated with molecular-level anomalies

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Asian Journal of Andrology 2015年第4期17卷 554-560页

作者： Peter Sutovsky Mahmoud Aarabi Antonio Miranda-Vizuete Richard Oko Division of Animal Science and departments of obstetrics Gynecology and Women's Health University of Missouri Columbia Missouri USA Department of HumanGenetics McGill University Quebec Canada Department of Biomedical and molecular Sciences Institute de Biomedicina de Sevilla Hospital Universitario Virgen delRocb/CSIC/Universidad de Sevilla Sevilla Spain Queens University Kingston Ontario Canada.

Biomarker-based sperm analysis elevates the treatment of human infertility and ameliorates reproductive performance in livestock. The negative biomarker-based approach focuses on proteins and ligands unique to defective spermatozoa, regardless of their morphological phenotype, lending itself to analysis by flow cytometry （FC）. A prime example is the spermatid specific thioredoxin SPTRX3/TXNDC8, retained in the nuclear vacuoles and superfluous cytoplasm of defective human spermatozoa. Infertile couples with high semen SPTRX3 are less likely to conceive by assisted reproductive therapies （ART） and more prone to recurrent miscarriage while low SPTRX3 has been associated with multiple ART births. Ubiquitin, a small, proteolysis-promoting covalent posttranslational protein modifier is found on the surface of defective posttesticular spermatozoa and in the damaged protein aggregates, the aggresomes of spermiogenic origin. Semen ubiquitin content correlates negatively with fertility and conventional semen parameters, and with sperm binding of lectins LCA （Lens culinaris agglutinin; reveals altered sperm surface） and PNA （Arachis hypogaealpeanut agglutinin; reveals acrosomal malformation or damage）. The Postacrosomal Sheath WWl Domain Binding Protein （PAWP）, implicated in oocyte activation during fertilization, is ectopic or absent from defective human and animal spermatozoa. Consequently, FC-parameters of PAWP correlate with ART outcomes in infertile couples and with fertility in bulls. Assays based on the above biomarkers have been combined into multiplex FC semen screening protocols, and the surface expression of lectins and ubiquitin has been utilized to develop nanoparticle-based bull semen purification method validated by field artificial insemination trials. These advances go hand-in-hand with the innovation of FC-technology and genomics/proteomics-based biomarker discovery.

关键词： artificial insemination biomarker fertility fertilization flow cytometry infertility nanotechnology oocyte activation Postacrosomal Sheath WWI Domain Binding Protein sperm SPTRX3 thioredoxin ubiquitin

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Leukocyte driven-decidual angiogenesis in ***

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Cellular & molecular Immunology 2014年第6期11卷 522-537页

作者： Patricia DA Lima Jianhong Zhang Caroline Dunk Stephen J Lye B Anne Croy Ottawa Hospital Research Institute The Ottawa Hospital General Campus Critical Care Wing Ottawa ON Canada Research Centre for Women's and Infants' Health Lunenfeld-Tanenbaum Research Institute Mount Sinai Hospital Toronto ON Canada Department of physiology and University of Toronto Toronto ON Canada Department of obstetrics and gynecology University of Toronto Toronto ON Canada Department of Biomedical and molecular Sciences Queen's University Kingston ON Canada

Successful pregnancy and long-term, post-natal maternal and offspring cardiac, vascular and metabolic health require key maternal cardiovascular adaptations over gestation. Within the pregnant decidualizing uterus, coordinated vascular, immunological and stromal cell changes occur. Considerable attention has been given to the roles of uterine natural killer （uNK） cells in initiating decidual spiral arterial remodeling, a process normally completed by mid-gestation in mice and in humans. However, leukocyte roles in much earlier, region specific, decidual vascular remodeling are now being defined. Interest in immune cell-promoted vascular remodeling is driven by vascular aberrations that are reported in human gestational complications such as infertility, recurrent spontaneous abortion, preeclampsia （PE） and fetal growth restriction. Appropriate maternal cardiovascular responses during pregnancy protect mothers and their children from later cardiovascular disease risk elevation. One of the earliest uterine responses to pregnancy in species with hemochorial placentation is stromal cell decidualization, which creates unique niches for angiogenesis and leukocyte recruitment. In early decidua basalis, the aspect of the implantation site that will cradle the developing placenta and provide the major blood vessels to support mature placental functions, leukocytes are greatly enriched and display specialized properties. UNK cells, the most abundant leukocyte subset in early decidua basalis, have angiogenic abilities and are essential for normal early decidual angiogenesis. The regulation of uNK cells and their roles in determining maternal and progeny cardiovascular health over ore^nancv and PostPartum are discussed.

关键词： angiokines blood vessel decidua endometrium natural killer cell receptors uterine natural killer cell

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The role of the gut microbiome and its metabolites in metabolic diseases

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Protein & Cell 2021年第5期12卷 360-373页

作者： Jiayu Wu Kai Wang Xuemei Wang Yanli Pang Changtao Jiang Department of obstetrics and gynecology Center for Obesity and Metabolic Disease ResearchSchool of Basic Medical SciencesThird HospitalPeking UniversityBeijing 100191China Center of Basic Medical Research Institute of Medical Innovation and ResearchPeking University Third HospitalBeijing 100191China Department of physiology and Pathophysiology School of Basic Medical SciencesPeking UniversityKey Laboratory of Molecular Cardiovascular ScienceMinistry of EducationBeijing 100191China

It is well known that an unhealthy lifestyle is a major risk factor for metabolic diseases,while in recent years,accumulating evidence has demonstrated that the gut microbiome and its metabolites also play a crucial role in the onset and development of many metabolic diseases,including obesity,type 2 diabetes,nonalcoholic fatty liver disease,cardiovascular disease and so *** microorganisms dwell in the gastrointestinal tract,which is a key interface for energy acquisition and can metabolize dietary nutrients into many bioactive substances,thus acting as a link between the gut microbiome and its *** gut microbiome is shaped by host genetics,immune responses and dietary *** metabolic and immune potential of the gut microbiome determines its significance in host health and ***,targeting the gut microbiome and relevant metabolic pathways would be effective therapeutic treatments for many metabolic diseases in the near *** review will summarize information about the role of the gut microbiome in organism metabolism and the relationship between gut microbiome-derived metabolites and the pathogenesis of many metabolic ***,recent advances in improving metabolic diseases by regulating the gut microbiome will be discussed.

关键词： gut microbiome metabolism metabolite immune regulation metabolic diseases

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