Association of the Verbal Rating Scale-Measured Dysmenorrhea with Nausea and Vomiting in Pregnancy: A Retrospective Cohort Study.

OBJECTIVES: Nausea and vomiting in pregnancy (NVP) is a common condition that reduces the quality of life by negatively affecting work and family life, physical and mental health, and economic well-being. However, its risk factors remain unclear. This study aimed to explore the association between NVP and verbal rating scale (VRS)-measured dysmenorrhea and to explore potential protective factors. METHODS: This retrospective cohort study was conducted from June 2018 to December 2020 at Tongji Hospital in Wuhan. Information on baseline characteristics, pregnancy-related history, periconceptional micronutrient supplementation, and obstetric outcomes were collected. The severity of dysmenorrhea was assessed using VRS. RESULTS: A total of 443 pregnant women were recruited and divided into the NVP group (n = 76) and the control group (n = 367). A significant association was observed between NVP and VRS-measured dysmenorrhea (c2=10.038, P = 0.007). After adjusting for covariates, the association between moderate/severe dysmenorrhea and NVP remained significant (OR 2.384; 95% CI 1.104-5.148, P = 0.004). First-trimester docosahexaenoic acid supplement (OR 0.443; 95% CI 0.205-0.960, P = 0.039) may be beneficial in reducing the risk of NVP. CONCLUSIONS: Women with moderate to severe dysmenorrhea have a higher risk of experiencing NVP during the first trimester. Periconceptional docosahexaenoic acid supplementation may play a protective role.

PINK1-mediated mitophagy induction protects against preeclampsia by decreasing ROS and trophoblast pyroptosis.

INTRODUCTION: Preeclampsia (PE) is a multisystemic disorder attributed to the excessive presentation of placenta-derived immunoinflammatory factors. PTEN-induced putative kinase 1 (PINK1)-mediated mitophagy participates in the development and persistence of the inflammation. We hypothesized that dysregulated mitophagy might be involved in the pathogenesis of PE by promoting the activation of trophoblast pyroptosis that augment inflammation. METHODS: The morphology of mitochondrial in placenta were observed by transmission electron microscopy. The localization of PINK1 in the placenta was determined by immunohistochemistry. The expression levels of PINK1, PARKIN, LC3B, and SQSTM1 and pyroptosis-related molecules were compared between normal pregnancies and PE. We used hypoxia/reoxygenation (H/R) to stimulate the trophoblast hypoxia environment. HTR-8/SVneo cells were transfected with PINK1 plasmid and si-PINK1, respectively, and then were treated with H/R, to determine whether PINK1 regulated ROS and HTR-8/Svneo pyroptosis. Finally, ROS production was inhibited by MitoTEMPO to observe whether the pro-pyroptosis effect of PINK1 knockdown is alleviated. RESULTS: Swollen mitochondrial were accumulated in the PE placentae. PINK1 is localized on villus trophoblast (VTs) and extravillous trophoblast (EVTs). PINK1-mediated mitophagy was abolished in the PE placenta, while the levels of pyroptosis were induced. H/R stimulation aggravated the downregulation of mitophagy and the up-regulation of pyroptosis. Overexpression of PINK1 mitigated H/R-induced upregulation of ROS and pyroptosis while silencing PINK1 did the opposite. Reducing ROS production can effectively resist the pro-pyroptosis effect of PINK1 knockdown. DISCUSSION: This study demonstrated that PINK1-mediated mitophagy might played a protective role in PE by reducing ROS and trophoblast pyroptosis.

Long-term outcomes of offspring from multiple gestations: a two-sample Mendelian randomization study on multi-system diseases using UK Biobank and FinnGen databases.

BACKGROUND: Assisted reproductive technologies (ART) have increased the incidence of multiple births, which can have a negative impact on maternal and offspring health. The study aimed to investigate the association between genetically predicted multiple birth and the risk of 42 common diseases of the nervous, psychiatric, cardiovascular, respiratory, digestive, and endocrine systems. METHODS: The study utilized two-sample Mendelian randomization (MR) analysis to explore the potential causal relationship between genetically predicted multiple birth and the genetically predicted risk of diseases. The study used the FinnGen and UK Biobank datasets for analysis. RESULTS: The study found no significant causal relationship between multiple birth and psychiatric disorders. However, the lower limits of the 95% confidence intervals for bipolar affective disorder and anxiety disorders were not robust, indicating a need for further investigation. The study found that multiple birth may be a strong risk factor for infantile cerebral palsy, and caution is necessary in both natural and ART multiple births. The study revealed a potential causal relationship between multiple birth and coronary heart disease, ischemic heart disease, and deep vein thrombosis, which may be related to abnormal intrauterine environments in multiple pregnancies. Surprisingly, multiple birth appears to have a protective effect against some respiratory diseases, such as chronic obstructive pulmonary disease and asthma. CONCLUSIONS: The study highlights the need for caution regarding the risk of infantile cerebral palsy, cardiovascular diseases, and psychiatric disorders in multiple birth. Our study can lead to the development of preventive strategies and improved clinical management for affected infants.

New Interpretation of Neonatal Outcomes by Phenotypically Classified Preterm Syndrome: A Retrospective Cohort Study.

OBJECTIVE: The global aim to lower preterm birth rates has been hampered by the insufficient and incomplete understanding of its etiology, classification, and diagnosis. This study was designed to evaluate the association of phenotypically classified preterm syndromes with neonatal outcomes; to what extent would these outcomes be modified after the obstetric interventions, including use of glucocorticoid, magnesium sulfate, and progesterone. METHODS: This was a retrospective cohort study conducted at Tongji Hospital (composed of Main Branch, Optical Valley Branch and Sino-French New City Branch) in Wuhan. A total of 900 pregnant women and 1064 neonates were retrospectively enrolled. The outcomes were the distribution of different phenotypes among parturition signs and pathway to delivery, the association of phenotypically classified clusters with short-term unfavorable neonatal outcomes, and to what extent these outcomes could be modified by obstetric interventions. RESULTS: Eight clusters were identified using two-step cluster analysis, including premature rupture of fetal membranes (PPROM) phenotype, abnormal amniotic fluid (AF) phenotype, placenta previa phenotype, mixed condition phenotype, fetal distress phenotype, preeclampsia-eclampsia & hemolysis, elevated liver enzymes, and low platelets syndrome (PE-E&HELLP) phenotype, multiple fetus phenotype, and no main condition phenotype. Except for no main condition phenotype, the other phenotypes were associated with one or more complications, which conforms to the clinical practice. Compared with no main condition phenotype, some phenotypes were significantly associated with short-term adverse neonatal outcomes. Abnormal AF phenotype, mixed condition phenotype, PE-E&HELLP phenotype, and multiple fetus phenotype were risk factors for neonatal small-for gestation age (SGA); placenta previa phenotype was not associated with adverse outcomes except low APGAR score being 0-7 at one min; mixed condition phenotype was associated with low APGAR scores, SGA, mechanical ventilation, and grade HI-W intraventricular hemorrhage (IVH); fetal distress phenotype was frequently associated with neonatal SGA and mechanical ventilation; PE-E&HELLP phenotype was correlated with low APGAR score being 0-7 at one min, SGA and neonatal intensive care unit (NICU) admission; multiple fetus phenotype was not a risk factor for the outcomes included except for SGA. Not all neonates benefited from obstetric interventions included in this study. CONCLUSION: Our research disclosed the independent risk of different preterm phenotypes for adverse pregnancy outcomes. This study is devoted to putting forward the paradigm of classifying preterm birth phenotypically, with the ultimate purpose of defining preterm phenotypes based on multi-center studies and diving into the underlying mechanisms.

Regulatory mechanisms underlying endoplasmic reticulum stress involvement in the development of gestational diabetes mellitus entail the CHOP-PPARα-NF-κB pathway.

OBJECTIVE: We investigated the proinflammatory functions of endoplasmic reticulum stress and peroxisome proliferator-activated receptor α (PPARα) in the development of gestational diabetes mellitus (GDM) and their relationship in regulating inflammation in GDM. METHODS: This study was performed on placentas of normal pregnant women, women with GDM, and HTR8 cells. Transmission electron microscopy, immunohistochemistry, Western blot analysis, and RT-PCR were performed to analyze ERS and PPARα expression on both normal and GDM pregnancy placentas. ELISA was performed to analyze inflammatory biomarkers. To generate models of the GDM-like state, placentas of normal pregnancy were treated with LPS and polyinosinic-polycytidylic acid (poly [I:C]). TG, CHOP plasmid, and CHOP siRNA were assessed as to their regulation of HTR8 cells to discern the relationship between ERS and PPARα in regulating the inflammation associated with GDM. RESULTS: ERS was elevated in GDM placentas, induced the secretion of IL-6 and TNF-α, and attenuated the expression of GLUT-4. PPARα was diminished in GDM placentas and inhibited the inflammatory responses via the NF-κB nuclear-transport process. 4-PBA reduced CHOP and augmented PPARα, and it decreased IL-6 and TNF-α in our GDM-like explant. However, with both 4-PBA and MK886 treatment, we noted no significant difference in CHOP expression. The level of PPARα was reduced, and that of NF-κB p65 in the nucleus was elevated with TG treatment in the HTR8/Svneo. Knockdown of CHOP increased PPARα and reduced NF-κB p65, while expression of PPARα declined, and that of NF-κB p65 rose with the application of CHOP when HTR8 cells were treated with TG. CONCLUSIONS: ERS contributes to the pathophysiology of GDM in pregnancy via the CHOP-PPARα-NF-κB-signalling pathway by inducing aberrant activation of inflammation and insulin resistance.

The role of chemerin in the regulation of cGAS-STING pathway in gestational diabetes mellitus placenta.

Recent studies already confirmed that placenta mitochondrial dysfunction is associated with the progression of gestational diabetes mellitus (GDM). Besides, a possible relationship between adipokine chemerin and disulfide-bond A oxidoreductase-like protein (DsbA-L) had been revealed, whereas the potential interaction remains unclear. In addition, very little is still known about the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway and its mechanisms of action in the context of GDM. The present study aims to investigate the underlying mechanism of cGAS-STING pathway and its regulatory relationship with chemerin in GDM. A total of 50 participants, including 25 cases of GDM patients and 25 pregnant women with normal glucose tolerance, were enrolled, and their placenta tissues at term labor were collected. Besides, an insulin resistance cell model was established on the human trophoblastic cell line to explore the molecular mechanism of chemerin on cGAS-STING pathway. Results showed that there were mitochondrial pathological changes in GDM placenta, accompanied by the decreased expression of DsbA-L, increased level of chemerin, and the activation of cGAS-STING pathway. In the insulin resistant cell model, overexpression of chemerin upregulated protein expression of DsbA-L, and recombinant chemerin presented time-dependent inhibition on the cGAS-STING pathway, but this effect was not dependent on DsbA-L. In conclusion, elevated chemerin is probably a protective mechanism, which may be a potential therapeutic strategy for GDM.

Role of melatonin receptor 1B gene polymorphism and its effect on the regulation of glucose transport in gestational diabetes mellitus.

Melatonin receptor 1B (MT2, encoded by the MTNR1B gene), a high-affinity receptor for melatonin, is associated with glucose homeostasis including glucose uptake and transport. The rs10830963 variant in the MTNR1B gene is linked to glucose metabolism disorders including gestational diabetes mellitus (GDM); however, the relationship between MT2-mediated melatonin signaling and a high birth weight of GDM infants from maternal glucose abnormality remains poorly understood. This article aims to investigate the relationship between rs10830963 variants and GDM development, as well as the effects of MT2 receptor on glucose uptake and transport in trophoblasts. TaqMan-MGB (minor groove binder) probe quantitative real-time polymerase chain reaction (qPCR) assays were used for rs10930963 genotyping. MT2 expression in the placenta of GDM and normal pregnant women was detected by immunofluorescence, western blot, and qPCR. The relationship between MT2 and glucose transporters (GLUTs) or peroxisome proliferator-activated receptor γ (PPARγ) was established by western blot, and glucose consumption of trophoblasts was measured by a glucose assay kit. The results showed that the genotype and allele frequencies of rs10830963 were significantly different between GDM and normal pregnant women (P<0.05). The fasting, 1-h and 2-h plasma glucose levels of G-allele carriers were significantly higher than those of C-allele carriers (P<0.05). Besides, the protein and messenger RNA (mRNA) expression of MT2 in the placenta of GDM was significantly higher than that of normal pregnant women (P<0.05). Melatonin could stimulate glucose uptake and GLUT4 and PPARγ protein expression in trophoblasts, which could be attenuated by MT2 receptor knockdown. In conclusion, the rs10830963 variant was associated with an increased risk of GDM. The MT2 receptor is essential for melatonin to raise glucose uptake and transport, which may be mediated by PPARγ.

Low-dose asprin use during pregnancy may be a potential risk for postpartum hemorrhage and increased blood loss: a systematic review and meta-analysis.

OBJECTIVE: The association between aspirin use during pregnancy and the risk of postpartum hemorrhage remains unclear. This study aimed to explore the incidence of postpartum hemorrhage and the amount of postpartum blood loss among women who used aspirin during pregnancy. DATA SOURCES: From inception to October 2022, this study searched the following databases: MEDLINE, Web of Science, Embase, and the Cochrane Central Register of Controlled Trials. STUDY ELIGIBILITY CRITERIA: Studies comparing pregnancy outcomes that covered the incidence of postpartum hemorrhage or the amount of postpartum blood loss in pregnancies with aspirin vs placebo (or no aspirin) were included. METHODS: Reviewers separately ascertained studies, obtained data, and gauged study quality. The meta-analysis was conducted using a random effects model owing to the probable heterogeneity of the included studies. The rates of postpartum hemorrhage or the mean amounts of postpartum blood loss were compared, and the odds ratios or mean differences with 95% confidence intervals were estimated. Of note, 2 parts performed both a pooled analysis of randomized controlled trials and cohort studies and a separate analysis of randomized controlled trials. RESULTS: Overall, 21 studies with 373,926 women were included in the postpartum hemorrhage part, and 7 studies with 10,163 women were included in the postpartum blood loss part. The results suggested that aspirin (dose 60-150mg a day) use during pregnancy was associated with an increased incidence of postpartum hemorrhage (odds ratio, 1.20; 95% confidence interval, 1.07-1.34). When only randomized controlled trials were retained, the results remained significant (odds ratio, 1.12; 95% confidence interval, 1.00-1.25). In the second part, higher total blood loss after delivery was obtained (mean difference, 12.85 mL; 95% confidence interval, 3.28-22.42), and the result was unaltered when cohort studies were eliminated (mean difference, 13.72 mL; 95% confidence interval, 4.63-22.81). The conclusions are more likely to be obtained in developed countries. CONCLUSION: Low-dose aspirin use during pregnancy is a potential risk of postpartum hemorrhage and does slightly increase the amount of postpartum blood loss. Without denying the combined value of aspirin, our conclusions raised an alarm for clinicians about postpartum hemorrhage in women using aspirin during pregnancy.

miR-17-5p Promotes Glucose Uptake of HTR8/SVneo Trophoblast Cells by Inhibiting TXNIP/NLRP3 Inflammasome Pathway.

Introduction: Gestational diabetes mellitus (GDM) is one of the common metabolic disorders of pregnancy and results in poor pregnancy outcomes for both mother and fetus. MiR-17-5p is considered as the strongest predictor of metabolic syndrome status, but the relationship between GDM and miR-17-5p remains unclear. TXNIP, which leads to activation of NLRP3, is considered as a potential target of miR-17-5p, and the miR-17-5p/TXNIP/NLRP3 axis has been shown to play a major role in the occurrence and development of many metabolic diseases but has not been validated in GDM. Methods: MiR-17-5p was detected by RT-qPCR. The expression of TXNIP and NLRP3 in placenta was detected by immunofluorescence, RT-qPCR and Western blot. To explore the effect of miR-17-5p on TXNIP and NLRP3 and glucose uptake of HTR8/SVneo cells, miR-17-5p mimic and miR-17-5p inhibitor were transfected to achieve overexpression and inhibition. The interaction between miR-17-5p and TXNIP was confirmed by dual-luciferase reporter assay. Besides, glucose consumption of trophoblast cells was detected by glucose assay kit. Results: MiR-17-5p expression was down-regulated, while the expression of TXNIP and NLRP3 was up-regulated in GDM placental tissues. MiR-17-5p targeted TXNIP and inhibited its expression. MiR-17-5p also regulated NLRP3 expression and glucose uptake of HTR8/SVneo cells, which could be reversed by overexpression of TXNIP, suggesting that miR-17-5p improved glucose uptake of HTR8/SVneo cells by TXNIP/NLRP3 axis. The results were consistent with the above findings in high-glucose treated HTR8/SVneo cells. Conclusion: Our results suggested that miR-17-5p ameliorates the glucose uptake of HTR8/SVneo cells by TXNIP/NLRP3 axis, which may provide a new idea for offspring health of GDM patients.

Effects of KCa channels on biological behavior of trophoblasts.

The Ca2+-activated potassium (KCa) channels are involved in many cellular functions, but their roles in trophoblasts are unclear. This study aimed to clarify the effects of KCa channels on the biological behavior of trophoblasts. The localization and expression of the three types of KCa channels, including large-conductance KCa channels (BKCa), intermediate-conductance KCa channels (IKCa), and small-conductance KCa channels (SKCa), were detected in human chorionic villi taken from pregnant women between 5 and 8 weeks of gestation (n = 15) and HTR-8/SVneo cells. The effects of KCa channels on proliferation, apoptosis, and migration of HTR-8/SVneo cells were examined by using the activators or inhibitors of KCa channels. Results showed that KCa channels were mainly localized on the membrane and in the cytoplasm of trophoblasts in human chorionic villi and HTR-8/SVneo cells. The proliferation and migration of HTR-8/SVneo cells were inhibited by activating KCa channels. Apoptosis of trophoblasts was promoted through activating BKCa channels but was not affected by neither activating nor inhibiting IKCa and SKCa channels. This study substantiated the abovementioned biological roles of KCa channels in trophoblast cells, which is fundamental to further research on whether dysfunction of KCa channels is involved in the pathogenesis of pregnancy-related complications.

Immunopathogenesis of patients with COVID-19: from the perspective of immune system 'evolution' and 'revolution'.

The pandemic caused by severe acute respiratory syndrome coronavirus 2 is sweeping the world, threatening millions of lives and drastically altering our ways of living. According to current studies, failure to either activate or eliminate inflammatory responses timely and properly at certain stages could result in the progression of the disease. In other words, robust immune responses to coronavirus disease 2019 (COVID-19) are critical. However, they do not theoretically present in some special groups of people, including the young, the aged, patients with autoimmunity or cancer. Differences also do occur between men and women. Our immune system evolves to ensure delicate coordination at different stages of life. The innate immune cells mainly consisted of myeloid lineage cells, including neutrophils, basophils, eosinophils, dendritic cells and mast cells; they possess phagocytic capacity to different degrees at different stages of life. They are firstly recruited upon infection and may activate the adaptive immunity when needed. The adaptive immune cells, on the other way, are comprised mainly of lymphoid lineages. As one grows up, the adaptive immunity matures and expands its memory repertoire, accompanied by an adjustment in quantity and quality. In this review, we would summarise and analyse the immunological characteristics of these groups from the perspective of the immune system 'evolution' as well as 'revolution' that has been studied and speculated so far, which would aid the comprehensive understanding of COVID-19 and personalised-treatment strategy.

TREM-1 amplifies trophoblastic inflammation via activating NF-κB pathway during preeclampsia.

INTRODUCTION: Excessive activation of maternal systemic inflammation is one of the underlying causes of pathology during the disease course of preeclampsia (PE). The triggering receptor expressed on myeloid cells-1 (TREM-1) participates in the development and persistence of inflammation. We hypothesized that dysregulated TREM-1 may be involved in the pathogenesis of PE by promoting the secretion of trophoblastic pro-inflammatory cytokines that augment inflammation. METHODS: The localization of TREM-1 in placenta and the extravillous trophoblast cell line (TEV-1) was determined by immunohistochemical staining. The expression level of TREM-1 and pro-inflammatory cytokines in placentas were compared between normal pregnancies and PE. We used lipopolysaccharide (LPS) to simulate trophoblastic inflammation. TEV-1 cells were transfected with TREM-1 plasmid and si-TREM-1 respectively, and then were incubated with LPS. The expression levels of pro-inflammatory cytokines and key molecules featured in nuclear transcription factor-kappaB (NF-κB) pathway were detected. Transwell assays were used to detect the effects of TREM-1 on cell migration and invasion. RESULTS: TREM-1 was localized on both villous trophoblasts (VTs) and extravillous trophoblasts (EVTs). TREM-1 and pro-inflammatory cytokines were up-regulated in preeclamptic placenta. Overexpression of TREM-1 promoted the activation of NF-κB pathway and the release of pro-inflammatory factors induced by LPS, and enhanced migration and invasion of TEV-1 cells. Inhibition of TREM-1 significantly attenuated LPS-induced effects and suppressed migration and invasion. DISCUSSION: This study suggested that TREM-1 was up-regulated in PE, and may promote the production of downstream inflammatory factors by activating NF-κB pathway in trophoblastic cells, thus exerting pro-inflammatory effects in the pathogenesis of PE.

Exploring the Immunopathogenesis of Pregnancy With COVID-19 at the Vaccination Era.

Since December 2019, Wuhan, China, has experienced an outbreak of coronavirus disease (COVID-19), which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Pregnant women are deductively considered to be in immunosuppressive condition for the safety of semi-allograft fetuses, which increases the risk of being infected by the virus. In this review, we analyzed the unique immunological characteristics of pregnant women and reviewed their known outcomes at different trimesters from the perspective of underlying mechanisms that have been studied and speculated so far.

Molecular evidence suggesting the persistence of residual SARS-CoV-2 and immune responses in the placentas of pregnant patients recovered from COVID-19.

OBJECTIVES: Recent studies have shown the presence of SARS-CoV-2 in the tissues of clinically recovered patients and persistent immune symptoms in discharged patients for up to several months. Pregnant patients were shown to be a high-risk group for COVID-19. Based on these findings, we assessed SARS-CoV-2 nucleic acid and protein retention in the placentas of pregnant women who had fully recovered from COVID-19 and cytokine fluctuations in maternal and foetal tissues. MATERIALS AND METHODS: Remnant SARS-CoV-2 in the term placenta was detected using nucleic acid amplification and immunohistochemical staining of the SARS-CoV-2 protein. The infiltration of CD14+ macrophages into the placental villi was detected by immunostaining. The cytokines in the placenta, maternal plasma, neonatal umbilical cord, cord blood and amniotic fluid specimens at delivery were profiled using the Luminex assay. RESULTS: Residual SARS-CoV-2 nucleic acid and protein were detected in the term placentas of recovered pregnant women. The infiltration of CD14+ macrophages into the placental villi of the recovered pregnant women was higher than that in the controls. Furthermore, the cytokine levels in the placenta, maternal plasma, neonatal umbilical cord, cord blood and amniotic fluid specimens fluctuated significantly. CONCLUSIONS: Our study showed that SARS-CoV-2 nucleic acid (in one patient) and protein (in five patients) were present in the placentas of clinically recovered pregnant patients for more than 3 months after diagnosis. The immune responses induced by the virus may lead to prolonged and persistent symptoms in the maternal plasma, placenta, umbilical cord, cord blood and amniotic fluid.

A Participant-assigned Interventional Research of Precesarean Internal Iliac Artery Balloon Catheterization for Managing Intraoperative Hemorrhage of Placenta Previa and Placenta Accreta Spectrum Disorders After Cesarean Section.

Placenta accreta spectrum disorder (PASD) and placenta previa (PP) are two of the most hideous obstetric complications which are usually associated with a history of cesarean section (CS). Moreover, women with PASD, PP and/or a cesarean scarred uterus are more likely to have adverse pregnancy outcomes, including blood transfusion, hysterectomy, pelvic organs damage, postpartum hemorrhage, disseminated intravascular coagulation, multi-organ dysfunction syndrome and even maternal or fetal death. This study aimed to investigate the efficacy of precesarean internal iliac artery balloon catheterization (BC) for managing severe hemorrhage caused by PASD and PP with a history of CS. This participant-assigned interventional study was conducted in Tongji Hospital. We recruited 128 women with suspected PASD, PP and a history of CS. Women in the BC group accepted precesarean BC of bilateral internal iliac arteries before the scheduled cesarean delivery. Women in the control group underwent a conventional cesarean delivery. Intraoperative hemorrhage, transfusion volume, radiation dose, exposure time, complications and neonatal outcomes were discussed. There were significant differences in calculated blood loss (CBL) between BC group and control group (1015.0±144.9 vs. 1467.0±171.0 mL, P=0.04). Precesarean BC could reduce intraoperative red blood cell (RBC) transfusion as compared with control group (799.5±136.1 vs. 1286.0±161.6 mL, P=0.02) and lessen the rate of using blood products (57.1% vs. 76.4%, P=0.02). The incidence of hysterectomy was also lower in BC group than in control group. Postpartum outcomes showed no significant differences between the two groups, except that postoperation hospitalization was longer in BC group than in control group (6.7±0.4 vs. 5.8±0.2 days, P=0.03). Precesarean BC of internal iliac artery is an effective method for managing severe hemorrhage caused by PASD and PP with a cesarean scarred uterus, as it could reduce intraoperative blood loss, lessen intraoperative RBC transfusions and potentially decrease hysterectomies.

Integrated analysis of multiple microarray studies to identify potential pathogenic gene modules in preeclampsia.

BACKGROUND: Preeclampsia is a life-threatening hypertensive disorder during pregnancy, while underlying pathogenesis and its diagnosis are incomplete. METHODS: In this study, we utilized the Robust Rank Aggregation method to integrate 6 eligible preeclampsia microarray datasets from Gene Expression Omnibus database. We used linear regression to assess the associations between significant differentially expressed genes (DEGs) and blood pressure. Functional annotation, protein-protein interaction, Gene Set Enrichment Analysis (GSEA) and single sample GSEA were employed for investigating underlying pathogenesis in preeclampsia. RESULTS: We filtered 52 DEGs and further screened for 5 hub genes (leptin, pappalysin 2, endoglin, fms related receptor tyrosine kinase 1, tripartite motif containing 24) that were positively correlated with both systolic blood pressure and diastolic blood pressure. Receiver operating characteristic indicated that hub genes were potential biomarkers for diagnosis and prognosis in preeclampsia. GSEA for single hub gene revealed that they were all closely related to angiogenesis and estrogen response in preeclampsia. Moreover, single sample GSEA showed that the expression levels of 5 hub genes were correlated with those of immune cells in immunologic microenvironment at maternal-fetal interface. CONCLUSIONS: These findings provide new insights into underlying pathogenesis in preeclampsia; 5 hub genes were identified as biomarkers for diagnosis and prognosis in preeclampsia.

The prenatal diagnosis and genetic counseling of chromosomal micro-duplication on 10q24.3 in a fetus: A case report and a brief review of the literature.

RATIONALE: Split-hand/split-foot malformation (SHFM), also known as ectrodactyly, is a congenital limb malformation affecting the central rays of the autopod extending to syndactyly, median clefts of the hands and feet, aplasia/hypoplasia of phalanges, metacarpals and metatarsals. Duplication of this 10q24 region is associated with SHFM3. While the clinical and genetic heterogeneity of SHFM makes the prenatal diagnosis and genetic counseling more challenging and difficult. PATIENT CONCERNS: A physically normal pregnant woman had a systemic ultrasound at the second trimester, only identified the deformity of both hands and feet on the fetus. DIAGNOSES: The fetus was diagnosed as sporadic SHFM3. INTERVENTIONS: After seeking advice from genetic counseling, she decided to terminate the pregnancy. The induction of infant was done after appearance of bipedal clefts, lobster-claw appearance and partial loss of phalanges and metacarpals, leaving behind 2nd finger in the left hand and the 5th in the right hand. Furthermore, collection of umbilical cord is recommended to this fetus for genome-wide detection. OUTCOMES: An outcome of the gene detection from abortion shows that there is variation in copy number in genome of chromosome 1 and chromosome 10. LESSONS: This case study confirms an association between SHFM3 and chromosomal micro-duplication on 10q24.3, and the extension of clinical spectrum of SHFM3. It also proposes some prenatal diagnosis and genetic counseling to help in planning and management in affected pregnancy. This will reduce the congenital and development abnormalities in birth rate, as well as relive the economic, psychological, and physical burden to the affected families.

Correction to: HSP20 Exerts a Protective Effect on Preeclampsia by Regulating Function of Trophoblast Cells Via Akt Pathways.

Li F, Xie Y, Wu Y, et al. HSP20 exerts a protective effect on preeclampsia by regulating function of trophoblast cells via Akt pathways. Reproduct Sci. 2019;26:961-971. doi:10.1177/1933719118802057.

Silencing of DsbA-L gene impairs the PPARγ agonist function of improving insulin resistance in a high-glucose cell model.

Disulfide-bond A oxidoreductase-like protein (DsbA-L) is a molecular chaperone involved in the multimerization of adiponectin. Recent studies have found that DsbA-L is related to metabolic diseases including gestational diabetes mellitus (GDM), and can be regulated by peroxisome proliferator-activated receptor γ (PPARγ) agonists; the specific mechanism, however, is uncertain. Furthermore, the relationship between DsbA-L and the novel adipokine chemerin is also unclear. This article aims to investigate the role of DsbA-L in the improvement of insulin resistance by PPARγ agonists in trophoblast cells cultured by the high-glucose simulation of GDM placenta. Immunohistochemistry and western blot were used to detect differences between GDM patients and normal pregnant women in DsbA-L expression in the adipose tissue. The western blot technique was performed to verify the relationship between PPARγ agonists and DsbA-L, and to explore changes in key molecules of the insulin signaling pathway, as well as the effect of chemerin on DsbA-L. Results showed that DsbA-L was significantly downregulated in the adipose tissue of GDM patients. Both PPARγ agonists and chemerin could upregulate the level of DsbA-L. Silencing DsbA-L affected the function of rosiglitazone to promote the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (PKB)/AKT pathway. Therefore, it is plausible to speculate that DsbA-L is essential in the environment of PPARγ agonists for raising insulin sensitivity. Overall, we further clarified the mechanism by which PPARγ agonists improve insulin resistance.