Associations between phthalate metabolites and cytokines in the follicular fluid of women undergoing in vitro fertilization.

Many studies have showed that phthalates have reproductive and embryonic toxicity, while the potential mechanisms are mostly unknown. Inflammation may play a mediating part in phthalate exposure and adverse reproductive endpoints. A cross-sectional survey was conducted to investigate the associations of phthalate metabolites with inflammatory cytokines in the follicular fluid (FF) of women undergoing in vitro fertilization (IVF). We determined the levels of eight phthalate metabolites and five cytokines in the FF of 76 women, including interleukin (IL)- 6, IL-8, IL-10, monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α). The associations of individual phthalate exposure with cytokines in FF samples were explored by multiple linear regression. We further evaluated the combined effects of multiple phthalate exposures on FF levels of cytokines by using Bayesian kernel machine regression (BKMR) models. We found that there was a positive relationship between mono-ethyl phthalate (MEP) and IL-6 in the FF (percent change:12.4%; 95% CI: 1.3%, 24.9%). In contrast, elevated mono-benzyl phthalate (MBzP), mono(2-ethylhexyl) phthalate (MEHP) and %MEHP levels were associated with decreased MCP-1. In the BKMR models, phthalate metabolite mixtures were positively associated with TNF-α when the mixtures were lower than 65th percentile compared with their medians. In the stratified analyses, MEHP was inversely associated with MCP-1 among women with BMI ≥ 23 kg/m2 (test for interaction <0.05). Our results suggest that certain phthalate metabolites or their mixtures may alter levels of inflammatory cytokines in the FF, and further research is necessary to elucidate the mechanisms underlying the relationship between phthalates exposure, ovarian dysfunction and adverse pregnancy outcomes.

Genetic analysis of developmental and epileptic encephalopathy caused by novel biallelic SZT2 gene mutations in three Chinese Han infants: a case series and literature review.

BACKGROUND: Developmental and epileptic encephalopathy (DEE) exhibits phenotypic and genetic heterogeneity. Biallelic variants of the SZT2 gene can lead to DEE18, of which few cases have been reported. This study aimed to analyze the potential pathogenic factors in three cases of DEE18. METHODS: Trio-whole exome sequencing and crystal structure simulation analysis were performed, along with a literature review of DEE18 cases. RESULTS: All three patients had compound heterozygous variants in the SZT2 gene (patient 1, c.2887A > G/c.7970G > A; patient 2, c.3508A > G/c.7936C > T; and patient 3, c.2489G > T/c.8640_8641insC). The variants were predicted to have structural effects on the protein. Particularly, c.3508A > G/p.Ser1170Gly may lead to impaired binding of SZT2 to GATOR1, potentially resulting in the overactivation of the mTORC1 signaling pathway, causing seizures. Through the literature review, we observed that 27 patients with DEE had different degrees of intellectual and developmental disorders (DDs), and the variants leading to protein truncation cause severe DD and refractory epilepsy. Therefore, the phenotypic severity of patients may be related to the residual activity of variant SZT2 protein. CONCLUSION: We provide recently developed knowledge on the DEE18 genotype-phenotype spectrum and suggest that gene detection is of great value for the accurate diagnosis of patients with early-onset epilepsy. Further research is required for the development of individualized interventions for patients with DEE.

Associations between exposure to phthalates and liver function among women undergoing assisted reproductive technology.

Phthalates can induce hepatotoxicity in animal studies. We aimed to assess the associations of individual and mixture of urinary phthalate metabolites with serum liver function indicators among 764 women undergoing assisted reproductive technology (ART). In linear models, we observed inverse correlations between urinary mono-benzyl phthalate and serum total protein (TP) as well as globulin (ß=-0.27 and -0.23, respectively, P<0.05). Additionally, negative associations were identified between mono-isobutyl phthalate and mono-butyl phthalate (MBP) and aspartate aminotransferase-to-alanine transaminase ratio (AST/ALT) (P<0.05). MBP and the sum of all phthalate metabolites (∑all.phth.m) were positively associated with bilirubin, with ß ranging from 0.14 to 0.47. Most phthalate metabolites were also positively related to gamma-glutamyl transferase (GGT) (all P<0.05). In Bayesian kernel machine regression models, phthalate mixture was positively associated with bilirubin and GGT, whereas inversely associated with AST/ALT and TP. Our results suggest that phthalate exposure may impair liver function among women undergoing ART.

Associations of personal care products use with reproductive outcomes of IVF/ICSI treatment.

Introduction: Personal care products (PCPs) contain a number of endocrine-disrupting chemicals (EDCs) that could potentially affect the reproductive function in women of childbearing age. However, studies focused on the effects of PCPs use on reproductive outcomes are very limited. The current study aimed to explore the relationships between PCPs use patterns and reproductive outcomes in women undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment. Methods: A total of 1500 women from the Tongji Reproductive and Environmental (TREE) study between December 2018 and January 2020 were included in this study. Participants provided characteristics of PCPs use within the previous three months. Retrieved oocyte number, mature oocyte number, two distinct pronuclei (2PN) zygote number, fertilization rate, cleavage rate, blastocyst formation rate, implantation, clinical pregnancy, miscarriage, and live birth were followed up as reproductive endpoints. Generalized linear regression model was utilized to assess the associations between various categories of PCPs use and reproductive endpoints of IVF/ICSI. Results: After adjusting for relevant covariates, women who used skin care products ≥14 times per week had a reduction of 22.4% in the maturation rate (95% CI: -39.2%, -1.6%) compared to participants who did not use skin care products. After transferring fresh embryos, women who used cosmetics 1-2 times per week (adjusted OR = 2.2, 95% CI: 1.0, 4.8) or 3-7 times per week (adjusted OR = 2.5, 95% CI: 1.2, 5.2) had a higher possibility of miscarriage than those who did not use cosmetics. There was negative association between the use of gel or soap and the cleavage rate among women aged < 30 years old (P for interaction = 0.01). Among women with BMI ≥ 24 kg/m2, the use of gel or soap was negatively associated with the blastocyst formation rate (P for interaction = 0.04), while cosmetics use was negatively associated with the maturation rate (P for interaction = 0.001). Conclusion: Our findings suggest that the use of PCPs in women of reproductive age have a potential adverse impact on IVF/ICSI outcomes, particularly skin care and cosmetic products.

SCN1B and SCN2B gene variants analysis in dravet syndrome patients: Analysis of 22 cases.

Previous research identified SCN1B variants in some cases of Dravet syndrome (DS). We investigated whether SCN1B and SCN2B variants are commonly happened in DS patients without SCN1A variants. A total of 22 DS patients without SCN1A variants and 100 healthy controls were enrolled in this genetic study. DNA from DS patients was sequenced by Sanger method in whole exons of SCN1B and SCN2B genes. We identified two exon variants (c.351C>T, p.G117G and c.467C>T, p.T156M), which were present both in 1000 egenomes database and in healthy controls with a frequency of 0.54% and 4%, 0.06% and 0%, respectively. Additionally, eight intron or 3 prime UTR variants showing benign clinical significance have also been identified. Our results suggest that variants of SCN1B and SCN2B may not be common causes of DS according to our data. Further large sample-size cohort studies are needed to confirm our conclusion.

[Influence of age, body weight and dose on sodium valproate plasma concentrations in children with epilepsy].

OBJECTIVE: Age, body weight and dose have been shown as important influencing factors for sodium valproate plasma concentrations. However it is unclear whether there is interaction among them and whether the interaction could influence sodium valproate plasma concentrations. This study aimed to evaluate the influence of age, body weight and dose on plasma concentrations of sodium valproate and the interaction among them. METHODS: One hundred and thirty-two children with epilepsy (age: 4 months-6 years, weight: 5-25 kg) were enrolled. Sodium valproate was administered at the dosage of 10-30 mg/kg/d. Plasma concentrations of sodium valproate were measured by high-performance liquid chromatography 3-5 days after administration. The relationship of sodium valproate plasma concentrations with age, body weight, and dose of sodium valproate was examined using variance analysis, pearson correlation analysis and stepwise regression analysis. RESULTS: Age (F=8.630, P<0.01), body weight (F=3.650, P<0.05) and dose of sodium valproate (F=11.720, P<0.01) were influencing factors for sodium valproate plasma concentrations. The interaction between age and oral dose (F=2.484, P<0.05) and the interaction of age and body weight with oral dose (F=4.923, P<0.01) had significant effects on sodium valproate plasma concentrations. Stepwise regression analysis showed that dose of sodium valproate and body weight were entered to the regression equation. CONCLUSIONS: Age, body weight and dose of sodium valproate as well as the interactions between age and dose and between age, body weight and dose were influencing factors for valproate plasma concentrations.

[An epidemiological study of 2,353 patients injured in motor vehicle accidents].

OBJECTIVE: To investigate the clinical conditions of the in-patients with motor-vehicle injury and survey the distribution features of the injuries. METHODS: The clinical records of 2,353 patients with motor-vehicle injuries who were hospitalized in a hospital in Shaoyang City of Hunan Province, China, within the period from 1997 to 2001, were collected and surveyed. The patients were diagnosed according to International Classification of Diseases-9th Revision (ICD-9) codes and statistical analysis was performed in an attempt to define the injury features of this cohort of patients. RESULTS: The patients with motor-vehicle injuries took up a fraction 3.16% of the total in-patients treated in this hospital (74,368) within the defined period, with a male to female ratio of 2.37:1.00. Subjects in the age range of 15 to 44 years were most likely to be involved in the accidents (55.9%), and in terms of occupation, farmers who lived outside the urban regions had the highest ratio in the total injured patients (34.0%). In the motor-vehicle accidents, the major injuries occurred in the head, usually with moderate severity when admitted into hospital (69.9%). CONCLUSION: Traffic accident is a crucial public health issue that severely affects the life quality of the wounded. Effective legislation and regulations should therefore be instituted, and relevant health education program be launched to control and prevent the occurrence of these accidents.

[Change of nuclear factor-kappaB activity in early burn injury and its significance].

OBJECTIVE: To study the change of nuclear factor-kappaB(NF-kappaB) activity in the blood leukocytes of rats in the early period after severe burn injury and its significance. METHODS: To examine the change of NF-kappaB activity in leukocytes of blood of rats in the early period(48 hours) after severe burn injury to show its relation with tumor necrosis factor-alpha(TNF-alpha) and intercellular adhesion molecule-1(ICAM-1). RESULTS: The activity of NF-kappaB after burn injury was increased than that was before burn injury, and reached the peak at the 12 hours. TNF-alpha, ICAM-1 and polymorphonuclear neutrophilic leucocytes(PMN) in plasma had the similar changeable patterns, and NF-kappaB had the positive correlation with TNF-alpha, ICAM-1 and PMN. CONCLUSION: The activity of NF-kappaB is increased in blood leukocytes in the early period after severe burn injury. It may play an important role in systemic inflammatory response syndrome(SIRS) and multiple organ dysfunction syndrome(MODS) after burn injury.

Effect of BPA on the germination, root development, seedling growth and leaf differentiation under different light conditions in Arabidopsis thaliana.

Bisphenol A (BPA) is a well-known environmental toxic substance, which exerts unfavorable effects through endocrine disruptor (ER)-dependent and ER-independent mechanisms to threaten ecological systems seriously. BPA may also interact with other environmental factors, such as light and heavy metals, to have a synergetic effect in plants. However, there is little data concerning the toxic effect of BPA on the primary producers-plants and its possible interaction with light-dependent response. Here, the effects of BPA on germination, fresh weight, tap root length, and leaf differentiation were studied in Arabidopsis thaliana under different parts of light spectrum (dark, red, yellow, green, blue, and white light). Our results showed that low-dose BPA (1.0, 5.0 µM) caused an increase in the fresh weight, the tap root length and the lateral root formation of A. thaliana seedlings, while high-dose BPA (10.0, 25.0 µM) show an inhibition effect in a dose-dependent manner. Unlike karrikins, the effects of BPA on germination fresh weight and tap roots length under various light conditions are similar, which imply that BPA has no notable role in priming light response in germination and early seedling growth in A. thaliana. Meanwhile, BPA exposure influences the differentiation of A. thaliana leaf blade significantly in a light-dependent manner with little to no effect in dark and clear effect under red illumination.

[Expression of recombinant human alanine aminotransferase (ALT) isoenzyme 2 and preparation of anti-ALT2 monoclonal antibody].

AIM: To clone and express human alanine aminotransferase 2 (ALT2) in E.coli Rosetta (DE3), and to prepare monoclonal antibodies(mAb) against ALT2 for diagnostic purpose. METHODS: The gene encoding alanine aminotransferase 2 (ALT2) was cloned from hepatoma carcinoma cell by RT-PCR, and then inserted into pET28a vector. Recombination plasmids (pET28a-ALT2) were transformed into E.coli BL21. Human ALT2 was expressed as His-tagged fusion proteins and purified by immobilized Ni(2+);-affinity chromatography. The purified fusion ALT2 protein was used as an antigen to prepare mAb against it. RESULTS: The fusion ALT2 protein was expressed in recombinant E.coli Rosetta (DE3). The enzymatic activity of purified His-tag ALT2 is over 10 000 U/L. Mice were immunized with the purified fusion ALT2 protein, and 5 mAbs against ALT2 were generated. CONCLUSION: Two mAbs with high specificity for ALT2 were selected for further quantitative diagnostic reagent development.