Prediction of preeclampsia using maternal circulating mRNAs in early pregnancy.

PURPOSE: Preeclampsia (PE) is one of the most common and serious complications of pregnancy, and novel methods for the early prediction of PE are needed for clinical application. METHODS: In this study, a circulating cell-free RNA (cfRNA) panel of target genes for PE prediction was designed and validated in a case-control cohort and a nested case-control cohort. The QPCR was applied to quantify the copy number of cfRNA, and the data were normalized as multiples of the median. Ratios of serum placental growth factor (PIGF) and soluble fms-like tyrosine kinase 1 (sFLT-1) were also measured, and transabdominal ultrasonography was conducted for subjects in the prospective cohort. Binary logistic regression models for PE prediction were constructed and tested. RESULTS: Our results revealed that the women with PE showed significant alterations in serum cfRNA profiles from early pregnancy onward and before the onset of PE symptoms. Compared with PIGF/sFLT-1 measurement and ultrasonographic imaging, cfRNA test can detect PE at a very early stage of pregnancy. The predictive model exhibited the best performance at gestation week 32, with a detection rate of 100%. At 12 weeks of gestation, the model still manifested an area under curve (AUC) of 0.9144, and sensitivity of 1.0000. If combined with clinical parameters and ultrasonographic indicators, the model can achieve the highest AUC for PE prediction at early gestation. CONCLUSION: Measurement of cfRNA can be used to effectively predict PE with high performance, providing an additional method for monitoring PE throughout the course of pregnancy.

Screening of placenta accreta spectrum disorder using maternal serum biomarkers and clinical indicators: a case-control study.

BACKGROUND: Placenta accreta spectrum (PAS) disorder is a major cause of postpartum hemorrhage-associated maternal and fetal death, and novel methods for PAS screening are urgently needed for clinical application. METHODS: The purpose of this study was to develop new methods for PAS screening using serum biomarkers and clinical indicators. A total of 95 PAS cases and 137 controls were enrolled in a case-control study as cohort one, and 44 PAS cases and 35 controls in a prospective nested case-control study were enrolled as cohort two. All subjects were pregnant women of Chinese Han population. Biomarkers for PAS from maternal blood samples were screened based on high-throughput immunoassay and were further validated in three phases of cohort one. Screening models for PAS were generated using maternal serum biomarkers and clinical indicators, and were validated in two cohorts. The expression levels of biomarkers were analyzed using histopathological and immunohistochemical (IHC) techniques, and gene expression was examined by QPCR in the human placenta. Binary logistic regression models were built, and the area under the curve (AUC), sensitivity, specificity, and Youden index were calculated. Statistical analyses and model building were performed in SPSS and graphs were generated in GraphPad Prism. The independent-sample t test was used to compare numerical data between two groups. For nonparametric variables, a Mann-Whitney U test or a X2 test was used. RESULTS: The results demonstrated that the serum levels of matrix metalloproteinase-1 (MMP-1), epidermal growth factor (EGF), and vascular endothelial growth factor-A (VEGF-A) were consistently higher, while the level of tissue-type plasminogen activator (tPA) was significantly lower in PAS patients compared with normal term controls and patients with pre-eclampsia (PE) and placenta previa (PP). IHC and QPCR analysis confirmed that the expression of the identified biomarkers significantly changed during the third trimester in human placenta. The generated screening model combining serum biomarkers and clinical indicators detected 87% of PAS cases with AUC of 0.94. CONCLUSIONS: Serum biomarkers can be used for PAS screening with low expense and high clinical performance; therefore, it may help to develop a practicable method for clinical prenatal PAS screening.

Effects of paternal exposure to cigarette smoke on sperm DNA methylation and long-term metabolic syndrome in offspring.

BACKGROUND: Although paternal exposure to cigarette smoke may contribute to obesity and metabolic syndrome in offspring, the underlying mechanisms remain uncertain. METHODS: In the present study, we analyzed the sperm DNA-methylation profiles in tobacco-smoking normozoospermic (SN) men, non-tobacco-smoking normozoospermic (N) men, and non-smoking oligoasthenozoospermic (OA) men. Using a mouse model, we also analyzed global methylation and differentially methylated regions (DMRs) of the DLK1 gene in paternal spermatozoa and the livers of progeny. In addition, we quantified DLK1 expression, executed an intra-peritoneal glucose tolerance test (IPGTT), measured serum metabolites, and analyzed liver lipid accumulation in the F1 offspring. RESULTS: Global sperm DNA-methylation levels were significantly elevated (p < 0.05) in the SN group, and the methylation patterns were different among N, SN, and OA groups. Importantly, the methylation level of the DLK1 locus (cg11193865) was significantly elevated in the SN group compared to both N and OA groups (p < 0.001). In the mouse model, the group exposed to cigarette smoke extract (CSE) exhibited a significantly higher global methylation DNA level in spermatozoa (p < 0.001) and on the DMR sites of Dlk1 in 10-week-old male offspring (p < 0.05), with a significant increase in Dlk1 expression in their livers (p < 0.001). In addition, IPGTT and LDL levels were significantly altered (p < 0.001), with elevated liver fat accumulation (p < 0.05) in F1 offspring. CONCLUSION: Paternal exposure to cigarette smoke led to increased global methylation of sperm DNA and alterations to the DMR of the DLK1 gene in the F1 generation, which may be inherited parentally and may perturb long-term metabolic function.

Uterine damage induces placenta accreta and immune imbalance at the maternal-fetal interface in the mouse.

INTRODUCTION: Placenta accreta spectrum (PAS) disorder is one of the major complications resulting in maternal death and serious adverse pregnancy outcomes. Uterine damage - principally that associated with cesarean section - is the leading risk factor for the development of PAS. However, the underlying pathogenesis of PAS related to uterine damage remains unclear. METHODS: For this study, we constructed a mouse PAS model using hysterotomy to simulate a cesarean section in humans. Pregnant mice were sacrificed on embryonic days 12.5 (E12.5) and E17.5. Trophoblast invasion and placental vascularization were analyzed using Hematoxylin-Eosin (H&E) staining and immunohistochemistry (IHC), and the proportions of immune cells at the maternal-fetal interface were analyzed using flow cytometry. We analyzed the expressions of genes in the decidua and placenta using RNA sequencing and subsequent validation by QPCR, and measured serum angiogenic factors by ELISA. RESULTS: Uterine damage led to increased trophoblast invasion and placental vascularization, with extensive changes to the immune-cell profiles at the maternal-fetal interface. The proportions of T and NK cells in the deciduas diminished significantly, with the decidual NK cells and M - 2 macrophages showing the greatest decline. The expression of TNF-α and IL4 was upregulated in the deciduas, while that of IFN-γ and IL10 was downregulated significantly. The expression of Mmp2, Mmp9, Mmp3, and Dock4 was significantly elevated in the placenta, and the serum levels of anti-angiogenic factors were significantly attenuated. DISCUSSION: Uterine damage can cause immune imbalance at the maternal-fetal interface, which may contribute to abnormal trophoblast invasion and enhanced vascularization of the mouse placenta.

Apolipoprotein A1-Related Proteins and Reverse Cholesterol Transport in Antiatherosclerosis Therapy: Recent Progress and Future Perspectives.

Hyperlipidemia characterized by abnormal deposition of cholesterol in arteries can cause atherosclerosis and coronary artery occlusion, leading to atherosclerotic coronary heart disease. The body prevents atherosclerosis by reverse cholesterol transport to mobilize and excrete cholesterol and other lipids. Apolipoprotein A1, the major component of high-density lipoprotein, plays a key role in reverse cholesterol transport. Here, we reviewed the role of apolipoprotein A1-targeting molecules in antiatherosclerosis therapy, in particular ATP-binding cassette transporter A1, lecithin-cholesterol acyltransferase, and scavenger receptor class B type 1.

[Bayesian network Meta-analysis of traditional Chinese medicine injections combined with antiviral western medicine in treatment of influenza].

To systematically evaluate the efficacy and safety of traditional Chinese medicine injections combined with antiviral wes-tern medicine in the treatment of influenza by Bayesian network Meta-analysis. Four Chinese databases(CNKI, Wanfang, VIP, CBM) and three English databases(PubMed, EMbase, Cochrane Library) were retrieved by computer for randomized controlled trials(RCT) about the comparison between the combined administration of traditional Chinese medicine injections with antiviral western medicine(or with placebo) and the single administration of antiviral western medicine in the treatment of influenza, or the comparison between two different traditional Chinese medicine injections combined with antiviral western medicine in the treatment of influenza. The retrieval time was from the establishment of the databases to July 2020. Two researchers independently screen out the literatures and extracted the data according to the inclusion criteria and exclusion criteria. The included studies were evaluated by the Cochrane 5.1 bias risk assessment tool, and data analysis was conducted by ADDIS 1.16.8 and Stata 14.0. A total of 49 literatures about 5 061 cases were included finally, involving six traditional Chinese medicine injections, namely Reduning Injection, Xiyanping Injection, Tanreqing Injection, Yanhuning Injection, Qingkailing Injection and Shuanghuanglian Injection. The results of network Meta-analysis,(1)in terms of total effective rate, 6 traditional Chinese medicine injections combined with antiviral western medicine was better than antiviral western medicine alone. In terms of probability sorting, Shuanghuanglian Injection combined with antiviral western medicine ranked first.(2)There was no significant statistical difference in adverse reaction rate among all groups, but Reduning Injection ranked first in the probability sorting, due to the least side effects.(3)In terms of antipyretic time, Yanhuning Injection, Xiyanping Injection and Tanreqing Injection combined with antiviral western medicine was better than antiviral western medicine alone and Xiyanping Injection ranked first in the probability sorting.(4)In terms of cough relief time, Qingkailing Injection and Tanreqing Injection combined with antiviral western medicine was better than antiviral western medicine alone and Qingkailing Injection was superior to Yanhuning Injection. Qingkailing Injection combined with antiviral western medicine ranked first in the probability sorting.(5)In terms of the length of hospital stay, Xiyanping Injection, Tanreqing Injection and Reduning Injection combined with antiviral western medicine was superior to antiviral western medicine alone, and Reduning Injection ranked first in the probability sorting due to the shortest hospital stay. Because of the small quantity and low quality of included studies, the results of this study shall be regarded cautiously and comprehensively. In the future, multi-center, large-sample and clinical randomized controlled trials shall be conducted to verify the results.

[Stable Isotope Characteristics and Vapor Source of Precipitation in the South and North Slopes of Wushaoling Mountain].

We analyze the stable isotope characteristics and vapor source of precipitation in a monsoon marginal area in the southern and northern slopes of Wushaoling Mountain, northwestern China, using 97 precipitation samples collected from October 2016 to October 2017. Correlation analysis and HYSPLIT model are used to study the characteristics of stable isotopes in precipitation, local meteoric water line equation, temperature and precipitation effects, and vapor source. The study found the following results. ① The slope and intercept of the southern slope local meteoric water line were lower than of those of the northern slope and global averages. ② Although the isotope temperature effects and seasonal effects of both slopes were obvious, the temperature effect of the northern slope was more obvious than of that of the southern slope. ③ The stable isotopes of precipitation during the summer on the northern slope and the precipitation on the southern slope<5 mm revealed that the precipitation effect was weak. There was no obvious precipitation effect in other seasons or in other precipitation levels on both slopes. ④ Vapor from the northwest and north accounted for>90% of the total. The northern slope was rarely affected by monsoon vapor, but the southern slope was affected by the southeast monsoon during the summer. Local water vapor recycling contributed to water vapor in the southern and northern slopes of Wushaoling Mountain. This study could improve the cognition of precipitation isotopic evolution in alpine regions, and lays a foundation for further research on isotope hydrology in cold and arid regions.

[Determination of constituents of polysaccharide and contents of saccharide from Mongolian medicine Agari-8].

The water soluble polysaccharide was extracted from Agari-8, and the contents of the water soluble polysaccharide were determined by phenyl hydrate-sulfuric acid method. The average recovery was 101.80%. The RSD was 0. 92Y. The components of the water soluble polysaccharide were identified by gas chromatography with: arabinose, xylose, mannose and glucose in the molar ratio of 0.40 : 0.10 : 5.67 : 22.78. Their IR and UV spectra were studied.

[Determination of constituents of polysaccharide and the content of saccharide in Mongolian medicine Garidi-15].

The present paper introuduces the method, with which the water-soluble polysaccharide was extracted with hot water from Garidi-15, the products were further purified with column chromatography on SephadexC-25, and the contents of water soluble polysaccharide were determined by phenyl hydrate-sulfuric acid method. The average recovery was 100.50%, and RSD was 0.82%. The components of water soluble polysaccharide were identified by gas chromatography as xylose, mannose, galactose and glucose in the molar ratio of 1.03 : 1.26 : 0.77 : 2.30. The water soluble polysaccharide was identified by IR spectrum and UV(200-400 nm) scanning spectrum. The IR spectrum indicates that there are characteristic absorption peaks of polysaccharides at 3 417.46, 2 928.65, 1 742.86, 1 643.69, 1 149.78, 1 078.19, 1 022.56 and 834.57 cm(-1), of which there are absorption peaks of pyranose at 1 078.19 and 1 022.56 cm(-1), and contain one characteristic absorption peak of alpha-pyranose indican band at 834.57 cm(-1). The UV scanning spectrum shows the obvious polysaccharide absorption peak at 280 nm, and indicates the existence of C=O bond.