The associations between prenatal phthalate exposure and childhood glycolipid metabolism and blood pressure: An updated systematic review and a pilot meta-analysis of prospective cohort studies.

This is the first pilot meta-analysis on the association of prenatal phthalate exposure with childhood cardiometabolic risks. A systematic literature search was performed in MEDLINE, Web of Science and CNKI (Chinese National Knowledge Infrastructure) until June 5, 2023. A total of seven studies with 5746 children (2646 girls and 3100 boys) were finally included. Four, three and two studies investigated the effects of maternal phthalate exposure on childhood blood pressure (BP), blood lipids and blood glucose profiles, respectively. The pilot meta-analysis suggested that di-2-ethylhexyl phthalate (DEHP) metabolite exposure was associated with a decrease in childhood z-systolic BP (SBP, ß = -0.169, 95% CI = -0.338-0.001). Furthermore, the pooled results showed negative relationships of prenatal ∑DEHP exposure with z-SBP (ß = -0.109, 95% CI = -0.163 to -0.055) and z-diastolic BP (DBP, ß = -0.126, 95% CI = -0.182 to -0.069) in girls. In addition, MEP exposure was associated with z-SBP in girls (ß = -0.227, 95% CI = -0.387 to -0.066). The pooled result showed a positive relationship between prenatal ∑DEHP exposure and triglycerides (ß = 0.103, 95% CI = 0.028-0.178). The overall results revealed that exposure to ∑DEHP throughout gestation was associated with a decrease in insulin (ß = -0.074, 95% CI = -0.144 to -0.004) and glucose (ß = -0.129, 95% CI = -0.199 to -0.058) in boys. Interestingly, there was an inverse relationship of prenatal mono- 3 -carboxypropyl phthalate (MCPP) exposure with glucose in pubertal boys (ß = -3.749, 95% CIs = -6.758 to -0.741) but not found in postpubertal children. In conclusion, prenatal phthalate exposure interfered with cardiovascular risk in children with gender-specific differences and was influenced by puberty. Overall, prenatal ∑DEHP was negatively associated with systolic blood pressure in girls and with insulin and glucose in boys but increased the level of triglycerides.

Causal relationships of neonatal jaundice, direct bilirubin and indirect bilirubin with autism spectrum disorder: A two-sample Mendelian randomization analysis.

Background: Multiple systematic reviews and meta-analyses have examined the association between neonatal jaundice and autism spectrum disorder (ASD) risk, but their results have been inconsistent. This may be because the included observational studies could not adjust for all potential confounders. Mendelian randomization study can overcome this drawback and explore the causal relationship between the both. Methods: We used the data of neonatal jaundice, direct bilirubin (DBIL), indirect bilirubin (IBIL), and ASD collected by genome-wide association study (GWAS) to evaluate the effects of neonatal jaundice, DBIL and IBIL on ASD by using a two-sample Mendelian randomized (MR). The inverse variance-weighted method (IVW) was the main method of MR analysis in this study. Weighted median method, MR-Egger regression and mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) test were used for sensitivity analysis. Results: There was no evidence of an effect of neonatal jaundice (OR, 1.002, 95% CI, 0.977-1.027), DBIL (OR, 0.970, 95% CI, 0.884-1.064) and IBIL (OR, 1.074, 95% CI, 0.882-1.308) on ASD risk by IVW test. In the weighted median method, MR-Egger regression and leave-one-out analysis, the results were robust and no heterogeneity or pleiotropy was observed. Conclusions: We found that neonatal jaundice, DBIL and IBIL were not associated with ASD in this study. However, this paper did not explore the effect of severity and duration of jaundice on ASD in different ethnic populations, which may require further research.

A study on the enrichment mechanism of three nitrophenol isomers in environmental water samples by charge transfer supramolecular-mediated hollow fiber liquid-phase microextraction.

To explore the mechanism of extraction and enrichment of three nitrophenol isomers by charge-transfer supramolecular synergistic three-phase microextraction system, a charge transfer supramolecular-mediated hollow fiber liquid-phase microextraction (CTSM-HF-LPME) combined with high-performance liquid chromatography-ultraviolet detector (HPLC-UV) method was established for the determination of real environmental water samples. In this study, the three nitrophenols (NPs) formed charge-transfer supramolecules with electron-rich hollow fibers, which promoted the transport of NPs in the three-phase extraction system and greatly increased the EFs of NPs. The relationships between the EFs of NPs and their solubility, pKa, apparent partition coefficient, equilibrium constant, and structural property parameters were investigated and discussed. At the same time, most of factors affecting the EFs of NPs were investigated and optimized, such as the type of extraction solvent, pH value of sample phase and acceptor phase, extraction time, and stirring speed. Under optimal conditions, the EFs of o-nitrophenol, m-nitrophenol, and p-nitrophenol were 163, 145, and 87, respectively. With good linearity in the range of 5 × 10-7 ~ 1 µg/mL, and the limit of detection of 0.1 pg/mL, the relative standard deviations of the method precision were lower than 7.4%, and the average recoveries were between 98.6 and 106.4%. This method had good selectivity and sensitivity, satisfactory precision, and accuracy and had been successfully applied to the trace detection of real water samples.

Compartmentalized regulation of NAD+ by Di (2-ethyl-hexyl) phthalate induces DNA damage in placental trophoblast.

Di (2-ethyl-hexyl) phthalate (DEHP) is a wildly used plasticizer. Maternal exposure to DEHP during pregnancy blocks the placental cell cycle at the G2/M phase by reducing the efficiency of the DNA repair pathways and affects the health of offsprings. However, the mechanism by which DEHP inhibits the repair of DNA damage remains unclear. In this study, we demonstrated that DEHP inhibits DNA damage repair by reducing the activity of the DNA repair factor recruitment molecule PARP1. NAD+ and ATP are two substrates necessary for PARP1 activity. DEHP abated NAD+ in the nucleus by reducing the level of NAD+ synthase NMNAT1 and elevated NAD+ in the mitochondrial by promoting synthesis. Furthermore, DEHP destroyed the mitochondrial respiratory chain, affected the structure and quantity of mitochondria, and decreased ATP production. Therefore, DEHP inhibits PARP1 activity by reducing the amount of NAD+ and ATP, which hinders the DNA damage repair pathways. The supplement of NAD+ precursor NAM can partially rescue the DNA and mitochondria damage. It provides a new idea for the prevention of health problems of offsprings caused by DEHP injury to the placenta.

Crystal film accelerated solvent microextraction (CF-ASME) for determination of flavonoids in natural products combined with high performance liquid chromatography.

A simple and efficient crystal film accelerated solvent microextraction (CF-ASME) technique was developed. In this study, the polyethylene pipe (PEP) with excellent comprehensive performance was used as the carrier of the extraction solvent, on which the crystal film was cured to improve its extraction capacity. The cured PEP was directly immersed in the sample phase solution to enrich the flavonoids (myricetin, quercetin, isorhamnetin, chrysin and kaempferide) in natural products. In addition, the extraction mechanism of the technique was elucidated. The important extraction variables were optimized including extraction solvent, the amount of NaCl required for crystal film preparation, salt concentration and pH of sample phase, stirring rate, extraction time, and volume of sample phase. Under the optimal conditions, the flavonoids were effectively enriched with the enrichment factors of 39.9-146.9 and they obtained good linearity with correlation coefficients higher than 0.99. The limits of detection were ranged between 0.5 and 30 ng/mL. Satisfactory accuracies (recoveries 89.4-104.8%) and precisions (relative standard deviations 5.8-11.2%) were also obtained. The proposed method was successfully applied for extraction and determination of flavonoids in natural products. Compared with the general accelerated solvent extraction methods, CF-ASME is simple to operate, green, high enrichment efficiency, which has a good application prospect.

A four-component combination derived from Huang-Qin Decoction significantly enhances anticancer activity of irinotecan.

Huang-Qin Decoction (HQD) is a classic prescription for diarrhea in Chinese medicine treatment. Recent studies have demonstrated that HQD and its modified formulation PHY906 could ameliorate irinotecan (CPT-11) induced gastrointestinal (GI) toxicity and enhance its anticancer therapeutic efficacy. Nevertheless, which constituents in HQD are effective is still unclear so far. The study aims to screen out the key bioactive components combination from HQD that could enhance the anticancer effect of CPT-11. First, the potential bioactive constituents were obtained through system pharmacology strategy. Then the bioactivity of each constituent was investigated synthetically from the aspects of NCM460 cell migration, TNF-α release of THP-1-derived macrophage and MTT assay in HCT116 cell. The contribution of each constituent in HQD was evaluated using the bioactive index Ei, which taken the content and bioactivity into comprehensive consideration. And then, the most contributing constituents were selected out to form a key-component combination. At last, the bioefficacy of the key-component combination was validated in vitro and in vivo. As a result, a key-component combination (HB4) consisting of four compounds baicalin, baicalein, glycyrrhizic acid and wogonin was screened out. In vitro assessment indicated that HB4 could enhance the effect of CPT-11 on inhibiting cell proliferation and inducing apoptosis in HCT116. Furthermore, the in vivo study confirmed that HB4 and HQD have similar pharmacological activity and could both enhance the antitumor effect of CPT-11 in HCT116 xenograft model. Meanwhile, HB4 could also reduce the CPT-11 induced GI toxicity.

[Clinical features and hospital costs of neonatal sepsis caused by bacteria and fungi: a comparative analysis].

OBJECTIVE: To study the clinical features and hospital costs of neonatal sepsis caused by Gram-positive (G(+)) bacteria, Gram-negative (G(-)) bacteria, and fungi. METHODS: The clinical data of 236 neonates with sepsis were analyzed retrospectively. Among these neonates, 110 had sepsis caused by G(+) bacteria, 68 had sepsis caused by G(-) bacteria, and 58 had sepsis caused by fungi. RESULTS: Full-term infants accounted for 62% and 38%, respectively, in the G(+) bacteria and G(-) bacteria groups, and preterm infants accounted for 86% in the fungi group. The neonates in the fungi group had significantly lower gestational ages and birth weights than those in the G(+) and G(-) bacteria groups (P<0.05). Compared with the G(+) bacteria group, the G(-) bacteria and fungi groups had significantly higher rates of multiple births (P<0.0125). Compared with the G(+) bacteria and fungi groups, the rates of premature rupture of membranes >18 hours, grade III amniotic fluid contamination, and early-onset sepsis in the G(-) bacteria group were significantly higher (P<0.0125). Compared with the G(-) bacteria and fungi groups, the G(+) bacteria group showed significantly higher rates of abnormal body temperature, omphalitis or herpes as the symptom suggesting the onset of such disease (P<0.0125). The fungi group had significantly higher incidence rates of apnea and low platelet count than the G(+) and G(-) bacteria groups (P<0.0125). The comparison of length of hospital stay and total hospital costs between any two groups showed that the fungi group had a significantly longer hospital stay and significantly higher total hospital costs than the G(+) and G(-) bacteria groups (P<0.05). CONCLUSIONS: Sepsis caused by G(+) bacteria mainly occurs in full-term infants, and most cases of sepsis caused by G(-) bacteria belong to the early-onset type. Sepsis caused by fungi is more common in preterm infants and low birth weight infants, and has high incidence rates of apnea and low platelet count, as well as a longer hospital stay and higher hospital costs than sepsis caused by bacteria.