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Objective: To explore the cytochrome P450 family 27 subfamily A member 1 (CYP27A1) gene mutations in Chinese women with intrahepatic cholestasis of pregnancy (ICP) and the correlation between CYP27A gene mutations and BA (bile acid) level changes.Methods: In this study, the entire coding region of the CYP27A1 gene was sequenced in 151 Han Chinese women with ICP and 1029 matched samples, and the pathogenicity of identified CYP27A1 gene mutations was judged through evolutionary conservation analysis, computational analysis and protein structure modeling. Finally, we verified the relationship between gene mutations and total serum bile acid (TBA) and cholesterol (CHOL) levels through experiments in cell culture.Results: We identified five heterozygous CYP27A1 missense mutations in five ICP samples. Three online tools, Polyphen-2, MutationTaster and SIFT, predicted that the five CYP27A1 mutations were pathogenic. Furthermore, all five mutations caused marked protein structural changes. Experiments in cells showed that the intracellular and medium levels of TBA in the mutant groups were lower than those in the wild-type group, while the CHOL levels were higher in all mutants except for the R158H mutant.Conclusions: CYP27A1 mutations are associated with the levels of TBA and CHOL, suggesting that CYP27A1 mutations contribute to abnormal total cholesterol and BA levels, which leads to ICP. [ABSTRACT FROM AUTHOR]

Contrary to the conventional viewpoint that "high housing price promotes industrial upgrading", this study finds that increasingly high housing prices are a pivotal factor that obstructs industrial value chain upgrading. Based on city-level data, micro-level data for Chinese industrial enterprises, and data for listed Chinese enterprises, this study examines the impacts of urban housing prices on value chain upgrading. We find that soaring housing prices in China since 2004 stunted industrial value chain upgrading, as indicated by the value-added rate. When housing prices increase by 100%, the enterprise value-added rate decreases by 12.4%. Intermediary mechanism analysis shows that housing price increases lead to innovation input suppression effects and resource misallocation effects, which in turn obstruct industrial value chain upgrading. Further analysis demonstrates that the impacts of housing price increases on industrial value chain upgrading, presenting an inverted-U shape, are varied in terms of time and region. Enterprises' value chain upgrading also showcases different degrees of sensitivity to housing price increases, due to their respective features. The conclusions of this study carry significant policy implications for the sound development of the real estate market and industrial upgrading in China, as well as in developing countries at large. [ABSTRACT FROM AUTHOR]

Background. In a global environment of increasing cesarean delivery rate, promoting vaginal delivery, reducing the rate of first cesarean section, and the incidence of vaginal delivery complications are the objectives of obstetric medical quality and safety in China. As a common obstetric complication, preeclampsia affects the safety of many pregnant women. It is the obstetrician's great responsibility to promote vaginal delivery and improve delivery outcomes in preeclampsia. To this end, we explored the roles of active labor management under the smart medical model in improving the outcomes of vaginal delivery for pregnant women with preeclampsia. Methods. The clinical data of 219 cases of preeclampsia pregnant women who delivered vaginally in our hospital from January 2017 to December 2020 were retrospectively analyzed. According to different labor process management, they were divided into study group (active labor process management group) and control group (normal labor process management group). Active labor process management methods included intrapartum ultrasound, central fetal heart rate monitoring, Doula delivery, labor analgesia, and quality of life care. The differences in delivery process, delivery outcome, bleeding causes, and hemostatic measures were compared between the two groups. Results. (1) The incidence of preeclampsia in our hospital showed an increasing trend in recent four years; (2) in smart hospitals, the active management of labor process reduced the probability of transferring to the cesarean section in preeclampsia pregnant women with vaginal trial failure; and (3) active labor process management reduced the rate of lateral episiotomy, decreased the postpartum hemorrhage volume within two hours, and improved the vaginal delivery outcome of preeclampsia pregnant women. Conclusions. In the era of the rapid development of the Internet, vigorously promoting the construction of smart hospitals and actively managing the delivery process can reduce the failure rate of vaginal trial delivery and improve the outcomes of vaginal delivery in preeclampsia women. [ABSTRACT FROM AUTHOR]

Objectives: To research the associations between fructose-bisphosphate aldolase B (ALDOB) gene polymorphisms and intrahepatic cholestasis of pregnancy (ICP) risk., Material and Methods: Whole-genome sequencing (WGS) was performed to detect ALDOB polymorphisms. Five web-available tools were employed to predict the effect of the site variant on the protein. Protein structure comparisons between the reference and ALDOB-modified samples were performed by SWISS-MODEL and Chimera 1.14rc, respectively., Results: We identified 28 genetic variants in the ALDOB gene. When the cut-off value of minor allele frequency (MAF) of loci was 0.001 in four databases, five missense variants, including rs747604233, rs759204107, rs758242037, rs371526091 and rs77718928, were reserved for subsequent analysis. These variants were absent from the 1029 control individuals. The influence of all five variants on protein function was predicted to be damaging by the abovementioned five prediction software programs. Bioinformatics analysis demonstrated that these five missense variants were highly conserved among vertebrates. Compared to the wild-type protein structure, all five mutated protein structures showed a slight change in the chemical bond lengths of the enzyme activity domains. The combined clinical data indicate that the variant group had a significantly older age (p = 0.038), a higher level of indirect bilirubin (IDBIL, p = 0.033), and lower counts of white blood cells (WBCs, p = 7.38E-05) and platelets (PLTs, p = 0.018) than the wild-type group., Conclusions: This is the first study to examine the associations between ALDOB polymorphisms and ICP disease in 249 Chinese patients with ICP. Our present study expands the understanding of the pathogenesis of ICP.

Background: Intrahepatic cholestasis of pregnancy (ICP) is characterized by pruritus and cholestasis in late pregnancy and results in adverse pregnancy outcomes, including preterm delivery and birth weight, which are affected by the genetic and environmental background. However, until now, the genetic architecture of ICP has remained largely unclear., Methods: Twenty-six clinical data points were recorded for 151 Chinese ICP patients. The data generated from whole-exome sequencing (WES) using the BGISEQ-500 platform were further analyzed by Burrows-Wheeler Aligner (BWA) software, Genome Analysis Toolkit (GATK), ANNOVAR tool, etc. R packages were used to conduct t-test, Fisher's test and receiver operating characteristic (ROC) curve analyses., Results: We identified eighteen possible pathogenic loci associated with ICP disease in known genes, covering ABCB4, ABCB11, ATP8B1 and TJP2. The loci Lys386Gln, Gly527Gln and Trp708Ter in ABCB4, Leu589Met, Gln605Pro and Gln1194Ter in ABCB11, and Arg189Ser in TJP2 were novel discoveries. In addition, WES analysis indicated that the gene ANO8 involved in the transport of bile salts is newly identified as associated with ICP. The functional network of the ANO8 gene confirmed this finding. ANO8 contained 8 rare missense mutations that were found in eight patients among the 151 cases and were absent from 1029 controls. Out of the eight SNPs, 3 were known, and the remaining five are newly identified. These variants have a low frequency, ranging from 0.000008 to 0.00001 in the ExAC, gnomAD - Genomes and TOPMED databases. Bioinformatics analysis showed that the sites and their corresponding amino acids were both highly conserved among vertebrates. Moreover, the influences of all the mutations on protein function were predicted to be damaging by the SIFT tool. Combining clinical data, it was found that the mutation group (93.36 µmol/L) had significantly (P = 0.038) higher total bile acid (TBA) levels than the wild-type group (40.81 µmol/L)., Conclusions: To the best of our knowledge, this is the first study to employ WES technology to detect genetic loci for ICP. Our results provide new insights into the genetic basis of ICP and will benefit the final identification of the underlying mutations.