早孕期监测子宫动脉多普勒参数在预测低危人群不良妊娠结局的价值

目的 建立妊娠11~13+6周子宫动脉多普勒参数在低危人群中的正常参考值，同时评估其对不良妊娠结局的预测价值。方法 收集2019年6月至2021年6月于我院行产前超声检查的妊娠11~13+6周孕妇，根据妊娠结局分组。收集两侧子宫动脉多普勒指标，包括搏动指数（PI）、阻力指数（RI）、舒张早期是否有切迹，以及孕妇基本临床资料和胎儿出生信息，将以上相关参数进行统计学分析。结果 最终纳入800例孕妇，包括正常妊娠结局组740例和不良妊娠结局组60例。两组孕妇体质量指数（BMI）、分娩孕周和胎儿出生体质量比较，差异均有统计学意义（均P＜0.05）。随着孕周的增加，子宫动脉两侧平均搏动指数（mPI）、平均阻力指数（mRI）和两侧舒张早期切迹检出率均呈逐渐下降的趋势。ROC曲线分析显示，mPI、mRI及两侧舒张早期切迹预测妊娠结局的曲线下面积（AUC）分别为0.542、0.574、0.521，三者联合预测妊娠结局的AUC为0.648；孕妇BMI、年龄mPI、mRI及两侧舒张早期切迹预测妊娠结局的AUC为0.751。结论 建立了低危人群在妊娠11~13+6周子宫动脉多普勒参数的正常参考值范围。在妊娠11~13+6周单纯应用子宫动脉多普勒参数预测妊娠结局的价值有限，将子宫动脉参数与临床相关指标结合可提高对不良妊娠结局的预测价值。     

Proteomics analysis of lysine crotonylation and 2-hydroxyisobutyrylation reveals significant features of systemic lupus erythematosus

Introduction/objectives

To seek significant features of systemic lupus erythematosus (SLE) by utilizing bioinformatics analysis.

Method

Liquid chromatography-tandem mass spectrometry (LC–MS/MS) was used to quantify lysine crotonylation (Kcr) and lysine 2-hydroxyisobutyrylation (Khib) in peripheral blood mononuclear cells (PBMCs) of systemic lupus erythematosus (SLE) patients and normal controls.

Results

Seventy-six differentially modified proteins (DMPs) dually modified by Kcr and Khib were identified between SLE patients and healthy people. GO enrichment analysis prompted significant enrichment of seventy-six DMPs in MHC class II protein complex binding and leukocyte migration. KEGG pathways were enriched in antigen processing and presentation pathway and leukocyte transendothelial migration pathway. Six DMPs (CLTC, HSPA1B, HSPA8, HSP90AB1, HSPD1, and PDIA3) were identified in antigen processing and presentation pathway, of which HSPA8 was the core protein. Significant changes of Kcr and Khib in HSPA8 may increase ATP hydrolysis and promote antigen binding to MHC II molecule. In leukocyte transendothelial migration pathway, 7 DMPs (ACTN1, ACTN4, EZR, MSN, RAC1, RHOA, and VCL) were identified. MSN was the protein with the most modification sites in this pathway. In amino terminal ferm region of MSN, Kcr and Khib expression change may lead to the adhesion between leukocytes and endothelial cells, which was an important step of leukocyte migration.

Conclusion

Kcr and Khib may promote the antigen presentation and jointly regulate the tissue damage mediated by leukocyte migration in SLE patients, which may play key roles in the pathogenesis of SLE probably.

Diffusion MRI changes in the anterior subventricular zone following chemoradiation in glioblastoma with posterior ventricular involvement

Journal of Neuro-Oncology - There is growing evidence that the subventricular zone (SVZ) plays a key role in glioblastoma (GBM) tumorigenesis. However, little is known regarding how the SVZ, which...     

GPER-induced signaling is essential for the survival of breast cancer stem cells

G protein-coupled estrogen receptor-1 (GPER), a member of the G protein-coupled receptor (GPCR) superfamily, mediates estrogen-induced proliferation of normal and malignant breast epithelial cells. However, its role in breast cancer stem cells (BCSCs) remains unclear. Here we showed greater expression of GPER in BCSCs than non-BCSCs of three patient-derived xenografts of ER⁻/PR⁺ breast cancers. GPER silencing reduced stemness features of BCSCs as reflected by reduced mammosphere forming capacity in vitro, and tumor growth in vivo with decreased BCSC populations. Comparative phosphoproteomics revealed greater GPER-mediated PKA/BAD signaling in BCSCs. Activation of GPER by its ligands, including tamoxifen (TMX), induced phosphorylation of PKA and BAD-Ser118 to sustain BCSC characteristics. Transfection with a dominant-negative mutant BAD (Ser118Ala) led to reduced cell survival. Taken together, GPER and its downstream signaling play a key role in maintaining the stemness of BCSCs, suggesting that GPER is a potential therapeutic target for eradicating BCSCs.