The risk factors of gestational diabetes mellitus in patients with polycystic ovary syndrome: What should we care.

ABSTRACT: The influencing factors of gestational diabetes mellitus (GDM) in the polycystic ovary syndrome (PCOS) patients remain unclear, we aimed to investigate the risk factors of GDM in patients with PCOS, to provide reliable evidence for the prevention and treatment of GDM in PCOS patients.PCOS patients treated in our hospital from January 1, 2019 to October 31, 2020 were included. The personal and clinical treatment details of GDM and no GDM patients were analyzed. Logistic regressions were performed to analyze the factors influencing the occurrence of GDM.A total of 196 PCOS patients were included, the incidence of GDM in patients with PCOS was 23.98%. There were significant differences in the age, body mass index, insulin resistance index, fasting insulin, testosterone, androstenedione, and sex hormone-binding protein between GDM and no GDM patients with PCOS (all P < .05), and no significant differences in the family history of GDM, the history of adverse pregnancy, and multiple pregnancies were found (all P > .05). Age ≥30 years (odds ratio (OR) 2.418, 95% confidence interval (CI) 1.181-3.784), body mass index ≥24 kg/m2 (OR 1.973, 95%CI 1.266-3.121), insulin resistance index ≥22.69 (OR 2.491, 95%CI 1.193-4.043), fasting insulin ≥22.71 mIU/L (OR 2.508, 95%CI 1.166-5.057), testosterone ≥2.85 nmol/L (OR 1.821, 95%CI 1.104-2.762), androstenedione ≥6.63 nmol/L (OR 1.954, 95%CI 1.262-2.844), sex hormone-binding protein <64.22 nmol/L (OR 1.497, 95%CI 1.028-2.016) were the independent risk factors of GDM in patients with PCOS (all P < .05). The incidence of preeclampsia, premature delivery, premature rupture of membranes, polyhydramnios, and postpartum hemorrhage in the GDM group was significantly higher than that of the no-GDM group (all P < .05). There was no significant difference in the incidence of oligohydramnios between the 2 groups (P = .057).The incidence of GDM in PCOS patients is high, and the measures targeted at the risk factors are needed to reduce the occurrence of GDM in patients with PCOS.

Risk factors of postpartum stress urinary incontinence in primiparas: What should we care.

ABSTRACT: Stress urinary incontinence (SUI) is a common clinical postpartum complication. It is necessary to explore the risk factors of postpartum SUI in primiparas to provide evidence support for preventing and reducing the occurrence of SUI.Primiparas who were delivered in our hospital from March 2019 to October 2020 were identified, the personal information and related treatment details of SUI and no-SUI primiparas were collected and analyzed. Logistic regression analyses were conducted to identify the risk factors of postpartum SUI in primiparas.A total of 612 primiparas were included, the incidence of SUI in primiparas was 32.03%. There were significant differences in the body mass index (BMI) before pregnancy, diabetes, abortion, delivery method, newborn's weight, epidural anesthesia, and duration of second stage of labor (all P < .05) between SUI and no-SUI group, and there were no significant differences in the age, BMI at admission, hypertension and hyperlipidemia SUI and no-SUI group (all P > .05). Logistic regression analyses indicated that BMI before pregnancy ≥24 kg/m2 (odds ratio [OR]: 2.109, 95% confidence interval [CI]: 1.042-4.394), diabetes (OR: 2.250, 95% CI: 1.891-3.544), abortion history (OR: 3.909, 95% CI: 1.187-5.739), vaginal delivery (OR: 2.262, 95% CI: 1.042-4.011), newborn's weight ≥3 kg (OR: 1.613, 95% CI: 1.095-2.316), epidural anesthesia (OR: 2.015, 95% CI: 1.226-3.372), and duration of second stage of labor ≥90 minutes (OR: 1.726, 95% CI: 1.084-2.147) were the risk factors of postpartum SUI in primiparas (all P < .05).The clinical incidence of SUI in primiparas is relatively high. In clinical practice, medical staff should conduct individualized early screening for those risk factors, and take prevention measures to reduce the occurrence of SUI.

Comparison of zebrafish in vitro and in vivo developmental toxicity assessments of perfluoroalkyl acids (PFAAs).

Perfluoroalkyl acids (PFAAs) are persistent environmental contaminants that are associated with various adverse health outcomes. Perfluorooctanoic acid (PFOA) is one of the most prominently detected PFAAs in the environment, which is now replaced with shorter chain carbon compounds including perfluorohexanoic acid (PFHxA) and perfluorobutyric acid (PFBA). The aim of this study was to compare the toxicity of four PFAAs as a function of chain length and head group (carboxylate versus sulfonate) with in vitro and in vivo zebrafish assessments, which were subsequently compared to other cell and aquatic models. Mortality rate increased with chain length (PFOA > PFHxA ≫ PFBA) in both whole embryo/larvae and embryonic cell models. The sulfonate group enhanced toxicity with perfluorobutane sulfonate (PFBS) showing higher toxicity than PFBA and PFHxA in both larvae and cells. Toxicity trends were similar among different aquatic models, but sensitivities varied. Discrepancies with other zebrafish studies were confirmed to be associated with a lack of neutralization of acidic pH of dosing solutions in these other investigations, demonstrating the need for rigor in reporting pH of exposure solutions in all experiments. The zebrafish embryonic cell line was also found to be similar to most other cell lines regardless of exposure length. Overall, results agree with findings in other cell lines and organisms where longer chain length and sulfonate group increase toxicity, except in investigations not neutralizing the exposure solutions for these acidic compounds.

Myclobutanil developmental toxicity, bioconcentration and sex specific response in cholesterol in zebrafish (Denio rerio).

The fungicide myclobutanil (MYC) is a common contaminant found in surface water. The aim of this study was to determine the acute toxicity, developmental effects, bioconcentration factor (BCF) and potential bio-molecular mechanisms of MYC toxicity in zebrafish. Susceptibility to MYC toxicity was life-stage dependent with adult fish being the most sensitive (96 h-LC50, 6.34 mg/L) followed by 72 h post-hatch (hph) larvae (8.90 mg/L), 12 hph larvae (20.53 mg/L) and embryos (42.54 mg/L). Zebrafish embryos and larvae (12 hph) responded with decreased hatching, heartbeat and growth, as well as abnormal spontaneous movement and development. BCFs were calculated by quantifying MYC concentrations from different tissues of adult zebrafish exposed to MYC for up to 11 days. Highest BCFs were obtained from gills (18.25 ±â€¯0.07), followed by viscera (16.78 ±â€¯0.04), head (13.13 ±â€¯0.08) and muscle (8.96 ±â€¯0.10). MYC (0.5 mg/L) inhibited gene expression related to cholesterol synthesis pathway, including 24-dehydrocholesterol reductase (DHCR24), 7-dehydrocholesterol reductase (DHCR7), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCRa), HMGCRb, farnesyl-diphosphate farnesyltransferase 1(FDFT1), squa-lene epoxidase (SQLE), isopentenyl-diphosphate delta isomerase 1 (IDI1) and CYP51, while no cholesterol changes were observed in the MYC treated group. These results will contribute to the literature assessing the environmental risk of MYC in aquatic environment.

Insight into the endocrine disrupting effect and cell response to butyltin compounds in H295R cell: Evaluated with proteomics and bioinformatics analysis.

The widespread use of organotin compounds (OTs) as biocides in antifouling paints and agricultural applications poses a serious threat to the ecosystem and humans. Butyltin compounds (BTs), especially tributyltin (TBT), are considered to be endocrine disrupting chemicals in marine organisms. The underlying mechanism of disrupting effects on mammals, however, has not been sufficiently investigated. To determine the effect and action of these biocides, the present study evaluated the effects of BTs on human adrenocortical carcinoma cells (H295R) with a focus on endocrine disrupting effect. Two-dimensional electrophoresis (2-DE) and subsequent mass finger printing were used to identify proteins expression profiles from the cells after exposure to 0.1µM BTs for 48h. In total, 89 protein spots showed altered expression in at least two treatment groups and 69 of these proteins were subsequently identified. Bioinformatic analysis of the proteins indicated that BTs involved in the regulation of hormone homeostasis, lipid metabolism, cell death, and energy production. IPA analysis revealed LXR/RXR (liver X receptor/retinoid X receptor) activation, FXR/RXR (farnesoid X receptor/retinoid X receptor) activation and fatty acid metabolism were the top three categories on which BTs acted and these systems play vital roles in sterol, glucose and lipid metabolism. The expression of LXR and FXR mRNA in H295R cells was stimulated by TBT, confirming the ability of TBT to activate this nuclear receptor. In summary, the differentially expressed proteins discovered in this study may participate in the toxic actions of BTs, and nuclear receptor activation and lipid metabolism may play important roles in such actions of BTs.

Methylmercury exposure alters RNA splicing in human neuroblastoma SK-N-SH cells: Implications from proteomic and post-transcriptional responses.

The neurotoxic effects of methylmercury (MeHg) have been intensively studied. However, the molecular mechanisms responsible for the neurotoxicity of MeHg are not fully understood. To decipher these mechanisms, proteomic and high-throughput mRNA sequencing (RNA-seq) technique were utilized, comprehensively evaluating the cellular responses of human neuroblastoma SK-N-SH cells to MeHg exposure. Proteomic results revealed that MeHg exposure interfered with RNA splicing via splicesome, along with the known molecular mechanisms of mercury-related neurotoxicity (e.g. oxidative stress, protein folding, immune system processes, and cytoskeletal organization). The effects of MeHg on RNA splicing were further verified using RNA-seq. Compared to control, a total of 658 aberrant RNA alternative splicing (AS) events were observed after MeHg exposure. Proteomics and RNA-seq results also demonstrated that mercury chloride (HgCl2) influenced the expression levels of several RNA splicing related proteins and 676 AS events compared to control. These results suggested that RNA splicing could be a new molecular mechanism involved in MeHg and HgCl2 neurotoxicity.

Improved Biocompatibility of Black Phosphorus Nanosheets by Chemical Modification.

Black phosphorus nanosheets (BPs) show great potential for various applications including biomedicine, thus their potential side effects and corresponding improvement strategy deserve investigation. Here, in vitro and in vivo biological effects of BPs with and without titanium sulfonate ligand (TiL4 ) modification are investigated. Compared to bare BPs, BPs with TiL4 modification (TiL4 @BPs) can efficiently escape from macrophages uptake, and reduce cytotoxicity and proinflammation. The corresponding mechanisms are also discussed. These findings may not only guide the applications of BPs, but also propose an efficient strategy to further improve the biocompatibility of BPs.

Gonadal intersex in smallmouth bass Micropterus dolomieu from northern Indiana with correlations to molecular biomarkers and anthropogenic chemicals.

Over the past decade, studies have shown that exposure to endocrine disrupting chemicals (EDCs) can cause gonadal intersex in fish. Smallmouth bass (Micropterus dolomieu) males appear to be highly susceptible to developing testicular oocytes (TO), the most prevalent form of gonadal intersex, as observed in various areas across the U.S. In this study, prevalence and severity of TO was quantified for smallmouth bass sampled from the St. Joseph River in northern Indiana, intersex biomarkers were developed, and association between TO prevalence and organic contaminants were explored. At some sites, TO prevalence reached maximum levels before decreasing significantly after the spawning season. We examined the relationship between TO presence and expression of gonadal and liver genes involved in sex differentiation and reproductive functions (esr1, esr2, foxl2, fshr, star, lhr and vtg). We found that vitellogenin (vtg) transcript levels were significantly higher in the liver of males with TO, but only when sampled during the spawning season. Further, we identified a positive correlation between plasma VTG levels and vtg transcript levels, suggesting its use as a non-destructive biomarker of TO in this species. Finally, we evaluated 43 contaminants in surface water at representative sites using passive sampling to look for contaminants with possible links to the observed TO prevalence. No quantifiable levels of estrogens or other commonly agreed upon EDCs such as the bisphenols were observed in our contaminant assessment; however, we did find high levels of herbicides as well as consistent quantifiable levels of PFOS, PFOA, and triclosan in the watershed where high TO prevalence was exhibited. Our findings suggest that the observed TO prevalence may be the result of exposures to mixtures of nonsteroidal EDCs.

Protein Corona Analysis of Silver Nanoparticles Exposed to Fish Plasma.

Nanoparticles (NPs) in contact with biological fluids experience changes in surface chemistry that can impact their biodistribution and downstream physiological impact. One such change involves the formation of a protein corona (PC) on the surface of NPs. Here we present a foundational study on PC formation following the incubation of polyvinylpyrrolidone-coated AgNPs (PVP-AgNPs, 50 nm) in the plasma of smallmouth bass (Micropterus dolomieu). PC formation increases with exposure time and is also affected by gender, with AgNPs incubated in male plasma having slightly thinner PCs and less negative zeta potentials than those incubated in female plasma. Proteomic analysis also revealed gender-specific differences in PC composition: in particular, egg-specific proteins (vitellogenin (VTG) and zona pellucida (ZP) were identified only in PCs derived from female plasma, raising the possibility of their roles in AgNP-related reproductive toxicity by promoting their accumulation in developing oocytes.

Vascular toxicity of silver nanoparticles to developing zebrafish (Danio rerio).

Nanoparticles (NPs, 1-100 nm) can enter the environment and result in exposure to humans and other organisms leading to potential adverse health effects. The aim of the present study is to evaluate the effects of early life exposure to polyvinylpyrrolidone-coated silver nanoparticles (PVP-AgNPs, 50 nm), particularly with respect to vascular toxicity on zebrafish embryos and larvae (Danio rerio). Previously published data has suggested that PVP-AgNP exposure can inhibit the expression of genes within the vascular endothelial growth factor (VEGF) signaling pathway, leading to delayed and abnormal vascular development. Here, we show that early acute exposure (0-12 h post-fertilization, hpf) of embryos to PVP-AgNPs at 1 mg/L or higher results in a transient, dose-dependent induction in VEGF-related gene expression that returns to baseline levels at hatching (72 hpf). Hatching results in normoxia, negating the effects of AgNPs on vascular development. Interestingly, increased gene transcription was not followed by the production of associated proteins within the VEGF pathway, which we attribute to NP-induced stress in the endoplasmic reticulum (ER). The impaired translation may be responsible for the observed delays in vascular development at later stages, and for smaller larvae size at hatching. Silver ion (Ag(+)) concentrations were < 0.001 mg/L at all times, with no significant effects on the VEGF pathway. We propose that PVP-AgNPs temporarily delay embryonic vascular development by interfering with oxygen diffusion into the egg, leading to hypoxic conditions and ER stress.

Nanosilver-coated socks and their toxicity to zebrafish (Danio rerio) embryos.

Silver nanoparticles (AgNPs) are being incorporated and are known to be released from various consumer products such as textiles. However, no data are available on the toxicity of AgNPs released from any of these commercial products. In this study, we quantified total silver released from socks into wash water by inductively coupled plasma mass spectrometry (ICP-MS) and determined the presence of AgNPs using transmission electron microscopy (TEM). We then exposed zebrafish (Danio rerio) embryos for 72 h to either this leachate ("sock-AgNP") or to the centrifugate ("spun-AgNP") free of AgNPs and compared their toxicity to that of ionic silver (Ag(+)). Our data suggest that AgNPs do get released into the wash water, and centrifugation eliminated AgNPs but did not decrease total silver concentrations, indicating that most of the silver in the sock-AgNP solution was in the ionic form. All embryos died during the first 24 h when exposed to undiluted sock-AgNP and spun-AgNP solutions resulting in significantly lower LC50 values (0.14 and 0.26 mg L(-1)) compared to AgNO3 (0.80 mg L(-1)). Similarly, at 72 hpf, both sock-derived solutions were more potent at affecting hatching and inducing abnormal development. These results suggest that both sock-AgNP and spun-AgNP solutions were more toxic than AgNO3. Previous studies have consistently shown the opposite, i.e., AgNPs are about 10 times less toxic that Ag(+). All together our results show that the high toxicity induced by the leachate of these socks is likely not caused by AgNPs or Ag(+). More studies are needed to evaluate the toxicity of the myriad of AgNP-coated commercial products that are now estimated to be close to 500.

Evaluation of acute and developmental effects of difenoconazole via multiple stage zebrafish assays.

Zebrafish, during embryo, larvae and adult stages were selected to investigate the potential environmental risk and aquatic toxicity of a widely used fungicide, difenoconazole. In addition to mortality, embryo development endpoints, teratogenic effects and behavior abnormity were measured. Finally, the developmental parameters of the adult fish were assessed after 14 days' exposure. This study concluded that the acute toxicity of difenoconazole to the three phases of zebrafish were larvae (1.17 mg/L) > adult fish (1.45 mg/L) > embryo (2.34 mg/L). A large suite of symptoms was induced in embryonic development by different dosages of difenoconazole, including hatching inhibition, abnormal spontaneous movement, slow heart rate, growth regression and morphological deformities. 0.50 mg/L of difenoconazole could cause significant body color blackening and decrease in the heart rate of zebrafish larvae over 24 h. In addition, 0.25 mg/L of difenoconazole apparently inhibited the growth weight of adult zebrafish measured after 14 days' exposure.