Fibroblast growth factor 1 ameliorates thin endometrium in rats through activation of the autophagic pathway.

Background: Thin endometrium is a reproductive disorder that affects embryo implantation. There are several therapies available for this disease, however they are not so effective. Fibroblast growth factor 1 (FGF1) is a member of fibroblast growth factor superfamily (FGFs), and it has been demonstrated that FGF1 expression was altered in samples collected from patients with thin endometrium. However, it is unclear if FGF1 could improve thin endometrium. The aim of this study was to investigate whether FGF1 have a therapeutic effect on thin endometrium. Methods: A model of thin endometrium induced by ethanol was constructed to investigate the effect and mechanism of action of FGF1 in thin endometrium. In the characterization experiments, 6-8 weeks female rats (n = 40) were divided into four groups: i) Control group; ii) Sham group; iii) Injured group; (iv) FGF1 therapy group. Endometrial tissues would be removed after three sexuel cycles after molding. Morphology and histology of the endometrium were evaluated by visual and hematoxylin and eosin staining. Masson staining and expression of α-SMA in endometrium showed the degree of endometrial fibrosis. Western blotting (PCNA、vWF and Vim) and immunohistochemistry (CK19 and MUC-1) demonstrated the effect of FGF1 on cell proliferation and angiogenesis. Moreover, immunohistochemistry (ER and PR) was used to explore the function of endometrium. The remaining rats (n = 36) were divided into three groups: i) Injured group; ii) FGF1 therapy group; and iii) 3-methyladenine. Western blotting (p38、p-p38、PI3K 、SQSTM1/p62、beclin-1 and LC3) was used to explore the mechanisms of FGF1. Results: In FGF1 therapy group, the morphology and histology of endometrium improved compared with the model group. Masson staining and the expression level of α-SMA showed that FGF1 could decrease the fibrotic area of endometrium. Besides, changes in ER and PR expression in the endometrium suggested that FGF1 could restore endometrium-related functions. Western blotting and immunohistochemistry revealed that PCNA, vWF, Vim, CK19 and MUC-1 were significantly increased after FGF1 treatment compared with the thin endometrium. In addition, Western blotting showed that p38, p-p38, PI3K, SQSTM1/p62, beclin-1 and LC3 levels were higher in FGF1 group than in the injured group. Conclusion: FGF1 application cured the thin endometrium caused by ethanol through autophagy mechanism.

Perinatal outcomes of twin emergency cerclage: comparison with expectant treatment and singleton emergency cerclage.

The present study aimed to evaluate the perinatal outcomes and influencing factors in twin pregnancies undergoing emergency cervical cerclage. The present retrospective cohort study included clinical data that were recorded between January 2015 and December 2021 at The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University (China). The study included data from 103 pregnancies (26 twin and 77 singleton pregnancies) that underwent emergency cerclage and 17 twin pregnancies that underwent expectant treatment. The median gestational age of twin emergency cerclage was significantly lower than that of singleton emergency cerclage, but higher than that of expectant treatment (28.5, 34.0 and 24.0 weeks, respectively). The median interval to delivery of twin emergency cerclage was significantly lower than that of singleton emergency cerclage, but significantly higher than that of expectantly treated twin pregnancies (37.0, 78.0 and 7.0 days, respectively).IMPACT STATEMENTWhat is already known on this subject? An important cause of premature birth is cervical insufficiency. Cervical cerclage extends the gestational period of women with cervical insufficiency. According to 2019 SOGC's No. 373-Cervical Insufficiency and Cervical Cerclage, both twin and single pregnancies benefit from emergency cerclage. However, there is minimal information about the pregnancy outcomes of emergency cerclage in twin pregnancies.What the results of this study add? This study shows that the outcomes of pregnancy in twin pregnancies undergoing emergency cerclage were better than that of expectant treatment but worse than that in singleton pregnancies undergoing emergency cerclage.What the implications are of these findings for clinical practice and/or further research? In this study, pregnant women with cervical insufficiency in twin pregnancies can benefit from emergency cerclage, we should treat those pregnant women as early as possible.

The effects of intrauterine growth on physical and intellectual development of one-year-old infants: a study on monochorionic twins with selective intrauterine growth restriction.

This study aimed to evaluate physical and intellectual development of one-year-old infants of monochorionic twins with selective intrauterine growth restriction (sIUGR). A total of 31 pairs of sIUGR twins ageing 1 year old were included in the study. Each pair of sIUGR twins was divided into low birthweight-twin group (L-twin group) and high birthweight-twin group (H-twin group) according to twins' birthweight. The differences in height, weight, head circumstance and body mass index (BMI) in each stage were statistically significant for all measures from birth until 1 year old (p < .05), and there was a disappointed catch-up growth in lighter twins. Psychomotor development index (PDI) and mental development index (MDI) at 1 year old were significantly different between the two groups (p < .05). Stepwise regression analysis showed that the effects of weight on both PDI and MDI were statistically significant (p < .05). Intrauterine growth inconsistencies in monochorionic twins with sIUGR persist until the first year of life and affect low-birthweight infants' physical and intellectual development.Impact StatementWhat is already known on this subject? Selective intrauterine growth restriction in monochorionic twins increases the risks of intrauterine foetal demise, preterm birth, caesarean delivery and adverse neonatal outcomes, especially in the smaller foetus.What do the results of this study add? Previous studies have concentrated on the clinical management of sIUGR, while little attention has been paid to the growth and development of twins after birth. Given the adverse neurobiological effects of suboptimal nutrition on the brain development, it is important to determine whether IUGR causes long-term cognitive deficits and physical retardation. The current study has assessed the physical and intellectual development of one-year-old infants of monochorionic twins with sIUGR.What are the implications of these findings for clinical practice and/or further research? Intrauterine growth inconsistencies in monochorionic twins with sIUGR persist until the first year of life and affect low-birthweight infants' physical and intellectual development. Further research on the longer-term effects of sIUGR is needed.

A blood-based miRNA signature for early non-invasive diagnosis of preeclampsia.

BACKGROUND: Preeclampsia (PE) is a multisystemic maternal syndrome with substantial maternal and fetal morbidity and mortality. Currently, there is no clinically viable non-invasive biomarker assay for early detection, thus limiting the effective prevention and therapeutic strategies for PE. METHODS: We conducted a discovery-training-validation three-phase retrospective and prospective study with cross-platform and multicenter cohorts. The initial biomarkers were discovered and verified in tissue specimens by small RNA sequencing and qRT-PCR. A miRNA signature (miR2PE-score) was developed using Firth's bias-reduced logistic regression analysis and subsequently validated in two independent multinational retrospective cohorts and two prospective plasma cohorts. RESULTS: We initially identified five PE-associated differentially expressed miRNAs from miRNA sequencing data and subsequently validated two miRNAs (miR-196b-5p and miR-584-5p) as robust biomarkers by association analysis with clinical characteristics and qRT-PCR in tissue specimens in the discovery phase. Using Firth's bias-reduced logistic regression analysis, we developed the miR2PE-score for the early detection of PE. The miR2PE-score showed a high diagnostic performance with an area under the receiver operating characteristic curve (AUROC) of 0.920, 0.848, 0.864, and 0.812 in training, internal, and two external validation cross-platform and multicenter cohorts, respectively. Finally, we demonstrated the non-invasive diagnostic performance of the miR2PE-score in two prospective plasma cohorts with AUROC of 0.933 and 0.787. Furthermore, the miR2PE-score revealed superior performance in non-invasive diagnosis compared with previously published miRNA biomarkers. CONCLUSIONS: We developed and validated a novel and robust blood-based miRNA signature, which may serve as a promising clinically applicable non-invasive tool for the early detection of PE.

Physical growth and intelligence development of discordant dizygotic twins from birth to preschool age: a prospective cohort study.

BACKGROUND: The majority of studies are limited to adverse perinatal outcomes and poor cognitive abilities in the short term in discordant monochorionic twins. METHODS: To determine whether small and large discordant dizygotic twins differ in physical growth and intelligence development and weight and height from birth up to 6 years of age were measured in 34 dizygotic twin pairs with ≥ 20% birth weight discordance. Mental developmental index (MDI) and psychomotor developmental index (PDI) were calculated at 1 year, while the Wechsler Intelligence Scale for Children-IV (WISC-IV) full-scale intelligence quotient (IQ) was assessed at the age of 6. RESULTS: The difference in height and weight in each stage differed significantly from birth to 72-months-old (P < 0.05), although there was disappointing catch-up growth in smaller twins. PDI but not MDI at 1 year of age was significantly different between the two groups (P < 0.05), and smaller twins experienced higher psychomotor retardation rates (P < 0.05). Also, the influence of height and weight on PDI was statistically significant (P < 0.05). No significant difference was detected in the WISC-IV full-scale IQ at the age of 6; however, the full-scale IQ may be affected by the history of suffocation and the S/D value (P = 0.011, P = 0.022). CONCLUSIONS: Intrauterine fetal growth and development lead to birth weight differences in twins and sustain an impact on the children's physical growth in height and weight from birth to preschool age, causing psychomotor developmental differences at 1 year of age. However, the differences in psychomotor development decrease gradually by the age of 6.

Leydig cell function in adult male rats is disrupted by perfluorotetradecanoic acid through increasing oxidative stress and apoptosis.

Perfluorotetradecanoic acid (PFTeDA) is a long-chain perfluoroalkyl compound with increased applications. Its effect on Leydig cell function and its underlying mechanism remain unclear. Male Sprague-Dawley rats (60 days old) were gavaged with PFTeDA at doses of 0, 1, 5, and 10 mg/kg/day from 60 to 87 days after birth. PFTeDA significantly reduced serum testosterone levels at 1 mg/kg and higher doses, while markedly increasing serum luteinizing hormone level at 10 mg/kg and follicle-stimulating hormone at ≥1 mg/kg. PFTeDA significantly reduced the sperm number at the cauda of epididymis at ≥1 mg/kg. PFTeDA also reduced the number of CYP11A1-positive Leydig cells due to increased apoptosis shown by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. PFTeDA significantly repressed the expression of Cyp17a1 and Star and their proteins at 1-10 mg/kg, while it increased the expression of Srd5a1 and its protein (an immature Leydig cell biomarker) at 10 mg/kg. PFTeDA markedly increased testicular malondialdehyde level, while inhibiting antioxidants (SOD1, SOD2, and CAT), triggering oxidative stress, thereby further inducing BAX and CASP3 while inhibiting BCL2, which led to cell apoptosis. PFTeDA also reduced DHH level secreted by Sertoli cells, which indirectly affected Leydig cell function. PFTeDA inhibited testosterone secretion in primary Leydig cells in vitro by increasing reactive oxygen species and inducing apoptosis at 50 µM. In conclusion, PFTeDA inhibits the function of Leydig cells by inducing oxidative stress and subsequently stimulating cell apoptosis.

Subclinical Hypothyroidism with Negative for Thyroid Peroxidase Antibodies in Pregnancy: Intellectual Development of Offspring.

Background: The adverse impact of maternal negative TPOAb of gestational subclinical hypothyroidism (SCH-TPOAb-) on the development of the offspring has not yet been clearly identified. A lingering controversy exists over the treatment of SCH-TPOAb- diagnosed during pregnancy. Therefore, this study was designed to evaluate the intellectual development of children of mothers who had SCH-TPOAb-. Methods: A number of 139 children were recruited; 112 children were born to SCH TPOAb- and 27 children were born to euthyroid TPOAb- mothers. Based on the mothers' thyrotropin (TSH) levels during pregnancy and whether or not they received levothyroxine (LT4) treatment, the children were assigned to four groups: Group A (2.5 mIU/L < TSH ≤4.0 mIU/L, n = 31) and Group B (4.0 mIU/L < TSH ≤10.0 mIU/L, n = 26), whose mothers were treated with LT4 before eight gestational weeks, and Group C (2.5 mIU/L < TSH ≤4.0 mIU/L, n = 27) and Group D (4.0 mIU/L < TSH ≤10.0 mIU/L, n = 28), whose mothers received no treatment. A total number of 27 children whose mother's serum TSH was <2.5 mIU/L and were TPOAb- during their pregnancy served as the control group (Group E). The intellectual development of two-year-old children was assessed and compared using the Gesell Development Diagnosis Scale. Results: The developmental quotient (DQ) in Group D was 8.67 lower than this in Group E (p < 0.001). More specifically, gross motor quotient, fine motor quotient, adaptability quotient (ABQ), language quotient (LQ), and individual social behavior quotient (ISBQ) of DQ in Group D were significantly lower than those in Group E. No significant differences were observed in DQ among Group A, Group B, Group C, and Group E (p > 0.05). Spearman's rank correlation analysis showed that DQ, FMQ, ABQ, LQ, and ISBQ were significantly negatively correlated with the TSH level (r = -0.417, -0.253, -0.273, -0.436, and -0.272; p < 0.05). In addition, multivariate logistic regression analysis revealed that mothers' education (short education), mothers' education (medium education), and TSH level (4.0 mIU/L < TSH ≤10.0 mIU/L) were both risk factors affecting the intellectual development of the offspring (p < 0.05). Conclusion: The effects of the intellectual development of the offspring with SCH-TPOAb- are related to the level of TSH. Standardized treatment for SCH-TPOAb- pregnant women before eight gestational weeks, whose TSH level was from 4.0 to 10.0 mIU/L, may significantly improve the intellectual development levels of the approximately two-year-old offspring. Although our study was a historical cohort study, the data analyzed provide the foundation for further investigation. Further prospective intervention trials with large numbers of participants are needed to confirm our conclusions. The Clinical Trial Registration number is 2021-K-84-02.

Inflammation/coagulopathy/fibrinolysis: Dynamic indicators of COVID-19 progression in patients with moderate COVID-19 in Wenzhou, China.

BACKGROUND: The majority of the coronavirus disease 2019 (COVID-19) non-survivors meet the criteria for disseminated intravascular coagulation (DIC). Although timely monitoring of clotting hemorrhagic development during the natural course of COVID-19 is critical for understanding pathogenesis, diagnosis, and treatment of the disease, however, limited data are available on the dynamic processes of inflammation/coagulopathy/fibrinolysis (ICF). METHODS: We monitored the dynamic progression of ICF in patients with moderate COVID-19. Out of 694 COVID-19 inpatients from 10 hospitals in Wenzhou, China, we selected 293 adult patients without comorbidities. These patients were divided into different daily cohorts according to the COVID-19 onset-time. Furthermore, data of 223 COVID-19 patients with comorbidities and 22 critical cases were analyzed. Retrospective data were extracted from electronic medical records. RESULTS: The virus-induced damages to pre-hospitalization patients triggered two ICF fluctuations during the 14-day course of the disease. C-reactive protein (CRP), fibrinogen, and D-dimer levels increased and peaked at day 5 (D) 5 and D9 during the 1st and 2nd fluctuations, respectively. The ICF activities were higher during the 2nd fluctuation. Although 12-day medication returned high CRP concentrations to normal and blocked fibrinogen increase, the D-dimer levels remained high on days 17 ±â€¯2 and 23 ±â€¯2 days of the COVID-19 course. Notably, although the oxygenation index, prothrombin time and activated partial thromboplastin time were within the normal range in critical COVID-19 patients at administration, 86% of these patients had a D-dimer level > 500 µg/L. CONCLUSION: COVID-19 is linked with chronic DIC, which could be responsible for the progression of the disease. Understanding and monitoring ICF progression during COVID-19 can help clinicians in identifying the stage of the disease quickly and accurately and administering suitable treatment.

Diagnostic value of pulse oximetry combined with cardiac auscultation in screening congenital heart disease in neonates.

OBJECTIVE: This study aimed to investigate the feasibility and reliability of pulse oximetry combined with cardiac auscultation in screening neonatal congenital heart disease (CHD). METHODS: This was a retrospective, observational, screening study. All newborns included in the study were at the Second Affiliated Hospital of Wenzhou Medical University from July 2019 to January 2020. Primary screening of CHD was conducted by pulse oximetry combined with cardiac auscultation assays. Indices, including sensitivity, specificity, the positive/negative predictive value, the positive/negative likelihood ratio, and the diagnostic odds ratio, were calculated. The area under the relative operating characteristic curve of the subjects was measured. RESULTS: A total of 3327 neonates were enrolled, among whom 139 were diagnosed with CHD and the incidence of CHD was 4.2%. The sensitivity, specificity, diagnostic odds ratio, and area under the relative operating characteristic curve of pulse oximetry combined with cardiac auscultation were 89.9%, 94.7%, 169.0, and 0.923, respectively. CONCLUSIONS: Pulse oximetry combined with cardiac auscultation is a novel screening method with acceptable accuracy and feasibility for neonatal CHD. This combination method is worth promoting widely.

Sex- and age-specific clinical and immunological features of coronavirus disease 2019.

To simultaneously determine clinical and immunological responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in young and old females and males, 681 coronavirus disease 2019 (COVID-19) patients and 369 normal controls (NCs) were analyzed based on age and sex classifications using multiple linear regression analysis. Compared to the age-matched NCs, both young and old male and female non-comorbid COVID-19 patients had lower lymphocyte counts and alanine aminotransferase (ALT) concentration, and only young male and female patients had lower neutrophil counts. Compared to young patients, both old males and females had significantly higher plasma ALT and AST concentrations. Compared to young and old females, age-matched males had higher plasma ALT and AST concentrations, but only young males had higher C-reactive protein (CRP) concentration. Compared to females, old males, but not young males, showed higher incidence of critical illness. Compared to young patients, old females had more leukocyte and neutrophil counts above the normal upper limit and B cell count below the normal lower limit (NLL), while old males had more lymphocyte and natural killer (NK) cell counts below the NLL. No sex or age associations with B cell and NK cell counts were observed. However, there were age-dependent decreases in CD8+ T-cell counts in both male and female COVID-19 patients. Age was negatively associated with CD8+ T cell counts but positively associated with neutrophil count, CRP, ALT, and AST concentrations, and sex (females) was negatively associated with neutrophil count, CRP, ALT, and AST concentrations. The present study suggests that SARS-CoV-2 infection mainly induced 1) beneficial sex (female)-related differences regarding reduced COVID-19 disease severity and negative associations with inflammatory responses and liver damage, and 2) harmful age-related differences relating to negative associations with CD8+ T cell count and positive associations with inflammatory responses and liver damage. Thus, sex and age are biological variables that should be considered in the prevention and treatment of COVID-19.

Age cohorts stratified according to age-distributions of COVID-19 morbidity statistics identify uniquely age-dependent CD3+CD8+ T-cell lymphocytopenia in COVID-19 patients without comorbidities on admission.

If age boundaries are arbitrarily or roughly defined, age-related analyses can result in questionable findings. Here, we aimed to delineate the uniquely age-dependent immune features of coronavirus disease 2019 (COVID-19) in a retrospective study of 447 patients, stratified according to age distributions of COVID-19 morbidity statistics into well-defined age-cohorts (2-25y, 26-38y, 39-57y, 58-68y, and 69-79y). Age-dependent susceptibilities and severities of the disease were observed in COVID-19 patients. A comparison of the lymphocyte counts among the five age-groups indicated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection led to age-dependent lymphopenia. Among the lymphocyte subsets, the CD8+ T cell count alone was significantly and age-dependently decreased (520, 385, 320, 172, and 139 n/µl in the five age-groups, respectively). In contrast, the CD4+ T cell, B cell, and natural killer cell counts did not differ among age-cohorts. Age and CD8+ T cell counts (r=‒0.435, p<0.0001) were negatively correlated in COVID-19 patients. Moreover, SARS-CoV-2 infection age-dependently increased the plasma C-reactive protein concentrations (2.0, 5.0, 9.0, 11.6, and 36.1 mg/L in the five age-groups, respectively). These findings can be used to elucidate the role of CD8+ T cells in age-related pathogenesis and to help develop therapeutic strategies for COVID-19.

Kiwi Root Extract Inhibits the Development of Endometriosis in Mice by Downregulating Inflammatory Factors.

PURPOSE: To determine whether the kiwi root extract inhibits the development of endometriosis in mice by suppressing inflammatory factors. MATERIALS AND METHODS: The mouse model of endometriosis was induced by surgery after which the mice were continuously injected with the drug for 14 days. On the 14th day, the mice were sacrificed, and the peritoneal fluid was obtained for enzyme-linked immunosorbent assay. Endometrial ectopic tissue was weighed and analyzed by tissue immunochemistry, RT-PCR, western blotting, and gelatin zymography experiment. RESULTS: Kiwi root extract significantly reduced endometriotic lesion volume and downregulated the proinflammatory cytokines IL-6, IL-8, IL-1ß, and TNF-α, as well as the angiogenic factor VEGF-A. It also inhibited the mRNA and protein expression of COX-1 and COX-2, IL-6, TGF-ß1, EP2 receptor, and ER-ß in endometriotic lesions but did not affect the expression of MMP-9 and MMP-2. CONCLUSIONS: Kiwi root extract could significantly inhibit the growth of surgery-induced endometriosis in mice. Our results suggest that the kiwi root extract may inhibit the development and progression of ectopic endometrium through disruption of neovascularization and reducing inflammation, which may be beneficial in treating this common gynecological disease.

Meta-analysis of the genetic association between maternal GNB3 C825T polymorphism and risk of pre-eclampsia.

BACKGROUND: The relationship between the C825T polymorphism of GNB3 (encoding G-protein ß3 subunit) and pre-eclampsia risk is unclear. OBJECTIVE: To systematically explore the association between GNB3 C825T and pre-eclampsia. SEARCH STRATEGY: PubMed, EMBASE, Google Scholar, and Chinese National Knowledge Infrastructure (CNKI) databases were searched to September 1, 2020, using keywords including "GNB3 C825T" and "pre-eclampsia". SELECTION CRITERIA: Case-control and cohort studies investigating the relationship between GNB3 C825T polymorphism and pre-eclampsia were included. DATA COLLECTION AND ANALYSIS: Two reviewers collected the data independently and calculate odds ratios (ORs) with 95% confidence intervals (CIs). MAIN RESULTS: The meta-analysis involved eight studies from seven publications, including 2071 cases and 3419 controls. Overall analysis showed that GNB3 C825T was associated with increased pre-eclampsia risk in the recessive model (OR, 1.21; 95% CI, 1.01-1.44; P = 0.04). Subgroup analysis stratified by Hardy-Weinberg equilibrium revealed a relationship between GNB3 C825T and increased risk of pre-eclampsia in the allelic (OR, 1.66; 95% CI, 1.34-2.05; P < 0.001), homozygous (OR, 2.12, 95% CI, 1.04-4.32; P  = 0.04), dominant (OR, 1.91; 95% CI, 1.18-3.11; P = 0.009), and recessive (OR, 1.70; 95% CI, 1.03-2.81; P = 0.04) models. CONCLUSIONS: Maternal GNB3 C825T polymorphism seems to be a risk factor for pre-eclampsia.

Lipoxin A4 inhibits the development of endometriosis in a mouse model by suppressing local estradiol synthesis.

We investigated whether lipoxin A4 (LXA4) inhibits the development of endometriosis by suppressing local estradiol synthesis. An endometriosis mouse model was constructed by surgical transplantation to subcutanous tissue sites. The treatment group received daily injections of LXA4 (10 µg/Kg) for 21days after which lesions were recovered. We measured 17ß-HSD1, 17ß-HSD2, CYP11A1, CYP19A1, CYP17A1, and estrogen receptor mRNA expression levels using real-time RT-PCR. In addition, immunohistochemistry was performed to determine protein expression and localization. After LXA4 administration, the volume of endometrial lesions was significantly reduced. Administration of LXA4 resulted in a more rudimentary architecture with a reduced number of developed glands surrounded by a small amount of stroma. LXA4 downregulated the mRNA and protein expression levels of 17ß-HSD1, CYP11A1, CYP19A1, CYP17A1, ERα, and ERß. Furthermore, LXA4 downregulated the expression of ERß, aromatase expression, and 17ß-HSD1 enzyme activity, which affected local estradiol production, resulting in reduced endometriosis. Results from our endometriosis mouse model showed that treatment with LXA4 reduced expression of enzymes and receptors associated or implicated with estrogen-dependent regulation of extra-uterine tissue. We believe that LXA4 has a potential therapeutic value for the treatment of endometriosis.

Healthy neonate born to a SARS-CoV-2 infected woman: A case report and review of literature.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly discovered coronavirus that has generated a worldwide outbreak of infections. Many people with coronavirus disease-2019 (COVID-19) have developed severe illness, and a significant number have died. However, little is known regarding infection by the novel virus in pregnant women. We herein present a case of COVID-19 confirmed in a woman delivering a neonate who was negative for SARS-CoV-2 and related it to a review of the literature on pregnant women and human coronavirus infections. CASE SUMMARY: The patient was a 36-year-old pregnant woman in her third trimester who had developed progressive clinical symptoms when she was confirmed as infected with SARS-CoV-2. Given the potential risks for both the pregnant woman and the fetus, an emergency cesarean section was performed, and the baby and his mother were separately quarantined and cared for. As a result, the baby currently shows no signs of SARS-CoV-2 infection (his lower respiratory tract samples were negative for the virus), while the mother completely recovered from COVID-19. CONCLUSION: Although we presented a single case, the successful result is of great significance for pregnant women with SARS-CoV-2 infection and with respect to fully understanding novel coronavirus pneumonia.

Association between fetal growth restriction and maternal exposure to polybrominated diphenyl ethers.

Humans are exposed to polybrominated diphenyl ethers (PBDEs) via ingestion of food, dust inhalation, and dermal absorption. Exposure to PBDEs via the placenta and breast milk is a special and important pathway in infants. This nested case-control study aimed to investigate the levels of PBDEs in maternal serum and colostrum, and to assess the association between the occurrence of fetal growth restriction (FGR) and prenatal exposure to PBDEs. We recruited 293 mother-newborn pairs, including 98 FGR cases and 195 healthy controls in Wenzhou, China. Maternal serum and colostrum samples were collected during pregnancy and after delivery, respectively, and the levels of PBDEs were measured by gas chromatography-tandem mass spectrometry. The total levels of PBDEs in maternal serum and colostrum were found to be in equilibrium, but congener profiles of PBDEs in these matrices were different. Increased BDE-207, BDE-209, ∑BDE196-209 and ∑PBDEs levels in maternal serum and BDE-99, ∑BDE17-154 and ∑PBDEs levels in colostrum were correlated with decreased birth weight Z score. Increased concentrations of higher brominated BDEs in maternal serum (odds ratio (OR) = 1.010, 95%CI = 1.003-1.018) and low-to moderately brominated BDEs in colostrum (OR = 1.004, 95%CI = 1.000-1.009) were associated with increased risk of FGR, which showed an exposure-response relationship. In addition, infants with FGR were more exposed to PBDEs in colostrum after birth than healthy infants. Longitudinal birth cohort studies are needed to determine the prolonged effect of PBDEs exposure on the growth of FGR infants in the future.

Differentiation of human umbilical cord mesenchymal stem cells into Leydig-like cells with defined molecular compounds.

95% of the body's testosterone is produced by the Leydig Cells (LCs) in adult testis, and LC functional degradation can cause testosterone deficiency ultimately leading towards hypogonadism. The transplantation of LCs derived from stem cells is a very promising therapy to overcome the testosterone deficiency. The isolated umbilical cord mesenchymal stem cells (UMSCs) were identified by flow cytometry and adipogenic and osteogenic differentiation. Western blotting and reverse transcription polymerase chain reaction (RT-PCR) were used for the differentiated Leydig-like cell identification. The comparisons of the testosterone levels, gene expression levels, and cyclic adenosine monophosphate (cAMP) productions were performed through radioimmunoassay, quantitative polymerase chain reaction (qPCR), and cAMP assay kit, respectively. Here, it is stated that our isolated human UMSCs, which could positively express CD29, CD44, CD59, CD90, CD105, and CD166 but negatively express CD34 as well as could be differentiated into adipocytes and osteocytes, could be differentiated into Leydig-like cells (UMSC-LCs) using a novel differentiation method based on molecular compounds. The enrichment UMSC-LCs could secrete testosterone into the medium supernatant and produce considerable cAMP at the stimulation of luteinizing hormone (LH), and positively expressed LC lineage-typical markers LHCGR, SCARB1, SATR, CYP11A1, CYP17A1, HSD3B1, HSD17B3, and SF-1 as well as negatively expressed mesenchymal stem cell typical markers CD29, CD44, and CD105. The expression levels of NR3C4, PDGFRA, and NR3A1 in UMSC-LCs were higher than those of UMSCs and were comparable with LCs. These results illuminated that UMSCs could be differentiated into Leydig-like cells using the defined molecular compounds, which might further support MSC-derived Leydig cell transplantation therapy for testosterone insufficiency.

Differentiation of human adipose derived stem cells into Leydig-like cells with molecular compounds.

Leydig cells (LCs) are the primary source of testosterone in the testis, and testosterone deficiency caused by LC functional degeneration can lead to male reproductive dysfunction. LC replacement transplantation is a very promising approach for this disease therapy. Here, we report that human adipose derived stem cells (ADSCs) can be differentiated into Leydig-like cells using a novel differentiation method based on molecular compounds. The isolated human ADSCs expressed positive CD29, CD44, CD59 and CD105, negative CD34, CD45 and HLA-DR using flow cytometry, and had the capacity of adipogenic and osteogenic differentiation. ADSCs derived Leydig-like cells (ADSC-LCs) acquired testosterone synthesis capabilities, and positively expressed LC lineage-specific markers LHCGR, STAR, SCARB1, SF-1, CYP11A1, CYP17A1, HSD3B1 and HSD17B3 as well as negatively expressed ADSC specific markers CD29, CD44, CD59 and CD105. When ADSC-LCs labelled with lipophilic red dye (PKH26) were injected into rat testes which were selectively eliminated endogenous LCs using ethylene dimethanesulfonate (EDS, 75 mg/kg), the transplanted ADSC-LCs could survive and function in the interstitium of testes, and accelerate the recovery of blood testosterone levels and testis weights. These results demonstrated that ADSCs could be differentiated into Leydig-like cells by few defined molecular compounds, which might lay the foundation for further clinical application of ADSC-LC transplantation therapy.

Formyl-peptide receptor 2 suppresses proliferation, migration and invasion in human extravillous trophoblastic cells.

Although FPR2 receptor is distributed in the endometrium and placenta, its function in human extravillous trophoblastic (TEV-1) cells still remains enigmatic. In this study, overexpression of FPR2 was performed in TEV-1 cells. Then, CCK8 transwell and wound healing assays were used to assess the cell proliferation, migration and invasion, respectively. The results showed that FPR2 overexpression significantly inhibited proliferation, invasion and migration in TEV-1 cells. In addition, FPR2 overexpression significantly decreased mRNA and protein levels of integrin-linked kinase (ILK), nuclear factor-kappa B (NF--κB), matrix metalloproteinase 9 (MMP9) and vascular endothelial growth factor (VEGF) in TEV-1 cells. These findings indicated that FPR2 overexpression alters proliferation, migration and invasion in human extravillous trophoblastic cellsthrough the ILK/NF-κB signaling pathway; ideal FPR2 levels are important for TEV-1 cells functions.