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Objective To evaluate the effectiveness of alpha-fetoprotein variants (AFP-L2, AFP-L3) in fetal screening for Trisomy 18 in place of alpha fetoprotein (AFP). Methods A retrospective case-control study was conducted. Collectively, 39 pregnant women bearing Trisomy 18 fetuses and 48 pregnant women with clinically normal and healthy fetuses were included. The serum AFP-L2 and AFP-L3 concentrations were detected by enzyme-linked immunosorbent assays. The likelihood ratio method and Python software were used to construct the risk model with AFP, free β-hCG, AFP-L2, and AFP-L3 to predict Trisomy 18. Receiver operating characteristic (ROC) curves were used to determine the optimal cutoff value, while the area under the curve (AUC) was used to assess the screening performance of AFP-L2 and AFP-L3 for fetal Trisomy 18. Results Compared to values observed for the control group, AFP-L2 and AFP-L3 concentrations which were significantly higher (both p< .001) in pregnant women with Trisomy 18 fetuses were 7.95 ± 3.57 ng/mL and 2.53 ± 1.80 ng/mL, respectively. Comparisons across multiple modeling methods showed that the highest AUC of screened Trisomy 18 fetuses (0.992, 0.986, and 0.976) was yielded by AFP-L2 + AFP-L3 + free β-hCG, AFP-L2 + free β-hCG, and AFP-L3 + free β-hCG, with a sensitivity of 1.000 indicated in both instances. In different modeling methods, the order of AUC values was AFP-L2 + AFP-L3 + free β-hCG > AFP-L2 + free β-hCG > AFP-L3 + free β-hCG > AFP + free β-hCG. Conclusions AFP-L2 and AFP-L3 showed higher sensitivity and specificity as substitutes for AFP in screening Trisomy 18. These two markers indeed improved the screening efficiency and reduced the false positive rate, when compared with AFP only. [ABSTRACT FROM AUTHOR]

Histone deacetylases (HDACs) are validated targets for the development of anticancer drugs in epigenetics. In the discovery of novel HDAC inhibitors with anticancer potency, the 5-chloro-4-((substituted phenyl)amino)pyrimidine fragment is assembled as a cap group into the structure of HDAC inhibitors. The SAR revealed that presence of small groups (such as methoxy substitution) is beneficial for the HDAC inhibitory activity. In the enzyme inhibitory selectivity test, compound L20 exhibited class I selectivity with IC50 values of 0.684 µM (selectivity index of >1462), 2.548 µM (selectivity index of >392), and 0.217 µM (selectivity index of >4608) against HDAC1, HDAC2 and HDAC3 compared with potency against HDAC6 (IC50 value of >1000 µM), respectively. In the antiproliferative assay, compound L20 showed both hematological and solid cancer inhibitory activities. In the flow cytometry, L20 promoted G0/G1 phase cell cycle arrest and apoptosis of K562 cells. [ABSTRACT FROM AUTHOR]

Background: To evaluate the correlation between elevated maternal serum alpha-fetoprotein (AFP) in the second trimester and ischemic placental disease (IPD). Methods: A retrospective cohort study was conducted to analyze the data of 22,574 pregnant women who delivered in the Department of Obstetrics at Hangzhou Women's Hospital from 2018 to 2020, and were screened for maternal serum AFP and free beta-human chorionic gonadotropin (free ß-hCG) in the second trimester. The pregnant women were divided into two groups: elevated maternal serum AFP group (n = 334, 1.48%); and normal group (n = 22,240, 98.52%). Mann-Whitney U-test or Chi-square test was used for continuous or categorical data. Modified Poisson regression analysis was used to calculate the relative risk (RR) and 95% confidence interval (CI) of the two groups. Results: The AFP MoM and free ß-hCG MoM in the elevated maternal serum AFP group were higher than the normal group (2.25 vs. 0.98, 1.38 vs. 1.04) and the differences were all statistically significant (all P < .001). Placenta previa, hepatitis B virus carrying status of pregnant women, premature rupture of membranes (PROM), advanced maternal age (=35 years), increased free ß-hCG MoM, female infants, and low birth weight (RR: 2.722, 2.247, 1.769, 1.766, 1.272, 0.624, 2.554 respectively) were the risk factors for adverse maternal pregnancy outcomes in the elevated maternal serum AFP group. Conclusions: Maternal serum AFP levels during the second trimester can monitor IPD, such as IUGR, PROM, and placenta previa. Maternal women with high serum AFP levels are more likely to deliver male fetuses and low birth weight infants. Finally, the maternal age (=35 years) and hepatitis B carriers also increased maternal serum AFP significantly. [ABSTRACT FROM AUTHOR]