Predicting risk of blastocyst aneuploidy among women with previous aneuploid pregnancy loss: a multicenter-data-based multivariable model.

STUDY QUESTION: Can blastocyst aneuploidy be predicted for patients with previous aneuploid pregnancy loss (PAPL) and receiving preimplantation genetic testing for aneuploidy (PGT-A)? SUMMARY ANSWER: Multivariable logistic regression models were established to predict high risk of blastocyst aneuploidy using four identified factors, presenting good predictive performance. WHAT IS KNOWN ALREADY: Aneuploidy is the most common embryonic chromosomal abnormality leading to pregnancy loss. Several studies have demonstrated a higher embryo aneuploidy rate in patients with PAPL, which has suggested that PGT-A should have benefits in PAPL patients intending to improve their pregnancy outcomes. However, recent studies have failed to demonstrate the efficacy of PGT-A for PAPL patients. One possible way to improve the efficacy is to predict the risk of blastocyst aneuploidy risk in order to identify the specific PAPL population who may benefit from PGT-A. STUDY DESIGN, SIZE, DURATION: We conducted a multicenter retrospective cohort study based on data analysis of 1119 patients receiving PGT-A in three reproductive medical centers of university affiliated teaching hospitals during January 2014 to June 2020. A cohort of 550 patients who had one to three PAPL(s) were included in the PAPL group. In addition, 569 patients with monogenic diseases without pregnancy loss were taken as the non-PAPL group. PARTICIPANTS/MATERIALS, SETTING, METHODS: PGT-A was conducted using single nucleotide polymorphism microarrays and next-generation sequencing. Aneuploidy rates in Day 5 blastocysts of each patient were calculated and high-risk aneuploidy was defined as a rate of ≥50%. Candidate risk factors for high-risk aneuploidy were selected using the Akaike information criterion and were subsequently included in multivariable logistic regression models. Overall predictive accuracy was assessed using the confusion matrix, discrimination by area under the receiver operating characteristic curve (AUC), and calibration by plotting the predicted probabilities versus the observed probabilities. Statistical significance was set at P < 0.05. MAIN RESULTS AND THE ROLE OF CHANCE: Blastocyst aneuploidy rates were 30 ± 25% and 21 ± 19% for PAPL and non-PAPL groups, respectively. Maternal age (odds ratio (OR) = 1.31, 95% CI 1.24-1.39, P < 0.001), number of PAPLs (OR = 1.40, 95% CI 1.05-1.86, P = 0.02), estradiol level on the ovulation trigger day (OR = 0.47, 95% CI 0.30-0.73, P < 0.001), and blastocyst formation rate (OR = 0.13, 95% CI 0.03-0.50, P = 0.003) were associated with high-risk of blastocyst aneuploidy. The predictive model based on the above four variables yielded AUCs of 0.80 using the training dataset and 0.83 using the test dataset, with average and maximal discrepancies of 2.89% and 12.76% for the training dataset, and 0.98% and 5.49% for the test dataset, respectively. LIMITATIONS, REASONS FOR CAUTION: Our conclusions might not be compatible with those having fewer than four biopsied blastocysts and diminished ovarian reserves, since all of the included patients had four or more biopsied blastocysts and had exhibited good ovarian reserves. WIDER IMPLICATIONS OF THE FINDINGS: The developed predictive model is critical for counseling PAPL patients before PGT-A by considering maternal age, number of PAPLs, estradiol levels on the ovulation trigger day, and the blastocyst formation rate. This prediction model achieves good risk stratification and so may be useful for identifying PAPL patients who may have higher risk of blastocyst aneuploidy and can therefore acquire better pregnancy outcomes by PGT-A. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Natural Science Foundation of China under Grant (81871159). No competing interest existed in the study. TRIAL REGISTRATION NUMBER: N/A.

Degradation of Aflatoxin B1 in Peanut Oil by Ultraviolet-LED Cold-Light Irradiation and Structure Elucidation of the Degradation Products.

This study aimed to determine the efficiency of ultraviolet (UV)-LED cold light treatment on the degradation of aflatoxin (AF)B1 in peanut oils. The peanut oil samples obtained from different places in China and abroad were determined for AFB1 degradation efficiency of the UV-LED cold-light irradiation method. The degradation products were analyzed by ultra-high performance liquid chromatography coupled to quadrupole orbitrap high-resolution mass spectrometry (UPLC-Q-Exactive MS). The results indicated that the AFB1 content in all peanut oil samples decreased rapidly after 5 min of irradiation. Four main photodegradation products (C18H16O7, C17H14O7, C17H14O7, and C17H14O8) were identified using the established LC-MS method. Their chemical structures were postulated based on the LC-MS data. Also, the degradation pathways were proposed based on the data obtained. Oxidation and reduction reactions were mainly responsible for AFB1-decomposition. The reactions occurred at the furan and lactone rings. These findings demonstrated that UV-LED cold-light irradiation was an effective method for treating AFB1- contaminated peanut oil.

Kinetic Characteristics of Curcumin and Germacrone in Rat and Human Liver Microsomes: Involvement of CYP Enzymes.

Curcumin and germacrone, natural products present in the Zingiberaceae family of plants, have several biological properties. Among these properties, the anti-NSCLC cancer action is noteworthy. In this paper, kinetics of the two compounds in rat liver microsomes (RLMs), human liver microsomes (HLMs), and cytochrome P450 (CYP) enzymes (CYP3A4, 1A2, 2E1, and 2C19) in an NADPH-generating system in vitro were evaluated by UP-HPLC-MS/MS (ultrahigh-pressure liquid chromatography-tandem mass spectrometry). The contents of four cytochrome P450 (CYP) enzymes, adjusting by the compounds were detected using Western blotting in vitro and in vivo. The t1/2 of curcumin was 22.35 min in RLMs and 173.28 min in HLMs, while 18.02 and 16.37 min were gained for germacrone. The Vmax of curcumin in RLMs was about 4-fold in HLMs, meanwhile, the Vmax of germacrone in RLMs was similar to that of HLMs. The single enzyme t1/2 of curcumin was 38.51 min in CYP3A4, 301.4 min in 1A2, 69.31 min in 2E1, 63.01 min in 2C19; besides, as to the same enzymes, t1/2 of germacrone was 36.48 min, 86.64 min, 69.31 min, and 57.76 min. The dynamic curves were obtained by reasonable experimental design and the metabolism of curcumin and germacrone were selected in RLMs/HLMs. The selectivities in the two liver microsomes differed in degradation performance. These results meant that we should pay more attention to drugs in clinical medication-drug and drug-enzyme interactions.

Characterization of Moringa oleifera roots polysaccharide MRP-1 with anti-inflammatory effect.

Moringa oleifera is a mutli-purpose herbal plant which has attained enormous attention as a natural source of nutrients and folk medicine. This work aimed to get a novel polysaccharide, termed MRP-1, which was isolated from Moringa oleifera roots with hot water extraction method followed by ethanol precipitation and purified with DEAE-Sepharose Fast Flow column. Monosaccharide composition analysis based on GC-MS showed that MRP-1 mainly consisted of Rha, Ara, Fru, Xyl, Man and Gal in the molar ratio of 1.5:2.0:3.1:6.0:5.3:1.1. The Roman spectra, FT-IR and NMR analysis showed that the typical features of carbohydrates, such as α-Araf, α-Gly, ß-Galp, α-GalpA and ß-Gly was contained by MRP-1. The LPS-induced RAW264.7 macrophage cells were used to evaluate the anti-inflammatory activity of MRP-1. The result demonstrated that the increasing of NO and TNF-α production induced by LPS could be prevented by different concentrations of MRP-1 treatment. Moreover, the mRNA expression level of iNOS induced by LPS was decreased significantly (p < 0.05) by MRP-1 treatment while show no obvious effect on the COX-2 mRNA expression. This study may provide new possible application of Moringa oleifera root polysaccharide related to anti-inflammation.