Termination of a second-trimester pregnancy with placenta accreta spectrum disorder.

Background: The termination of pregnancy in patients with placenta accreta spectrum disorder (PASD) during the second trimester remains uncertain. In addition, interventional radiology techniques, such as arterial embolization and balloon placement, are potential options. We evaluated the outcomes of pregnancy termination in patients with PASD during the second trimester and the effectiveness of preoperative interventional radiology techniques.Methods: This retrospective study analyzed 48 PASD patients who underwent pregnancy termination during the second trimester between January 2016 and May 2021.Results: Of the 48 patients, 20 (41.67%) underwent transvaginal termination, whereas 28 (58.33%) underwent cesarean section. Notably, no significant differences were observed in success rates between the transvaginal termination and cesarean section groups (80.00% vs. 92.86%, P = 0.38). Furthermore, no statistically significant differences were observed in the success rates (94.12% vs 90.32%, P = 1.00) and blood loss (512.35 ± 727.00 ml vs 804.00 ± 838.98 ml, P = 0.23) between the artery embolization and non-embolization groups. In the vaginal termination group, statistically significant differences were observed in gestational weeks (16.70 ± 3.12 vs 22.67 ± 3.63, P < 0.01) and blood loss (165.00 ± 274.43 ml vs 483.64 ± 333.53 ml, P = 0.04) between the (artery embolization and non-embolization) subgroups. Conversely, in the cesarean section group, no significant differences were observed in gestational weeks (23.59 ± 3.14 vs 23.20 ± 4.37, P = 0.79) and blood loss (811.11 ± 879.55 ml vs 989.47 ± 986.52 ml, P = 0.76) between the subgroups.Conclusions: Further studies are needed to evaluate the efficacy of vaginal termination in PASD patients during the second trimester. Regarding cesarean termination, arterial embolization did not demonstrate increased effectiveness.

Phosphoglycerate mutase 5 promotes necroptosis in trophoblast cells through activation of dynamin-related protein 1 in early-onset preeclampsia.

OBJECTIVES: Placentae from patients with preeclampsia have increased susceptibility to necroptosis and phosphoglycerate mutase 5 (PGAM5) plays a role in many necrosis pathways. We determined whether PGAM5 promotes necroptosis of trophoblast cells and the underlying mechanisms in this study. METHODS: The injury model was established by treating JEG3 cells with hypoxia for 24 h. The functional measurements were assessed by the cell counting kit-8, propidium iodide (PI)/Annexin V staining, JC-1 staining and firefly luciferase ATP assay. The expression of proteins in human placentae and JEG3 cells was measured Western blot. PGAM5 was knocked down to study its role in hypoxia-induced necroptosis. RESULTS: The placentae from patients with preeclampsia showed up-regulation of PGAM5 and decreased levels of p-Drp1-S637, accompanied by increased necroptosis-relevant proteins expression. The expression of PGAM5 in JEG3 cells was up-regulated under hypoxia, which promoted dephosphorylation of Drp1 at Serine 637 residue, mitochondrial dysfunction (elevated ROS level and reduced mitochondrial membrane potential and ATP content) and cellular necroptosis (increased PI+ /Annexin V+ cells and decreased cell viability), accompanied by increased expression of necroptosis-relevant proteins; knockdown of PGAM5 attenuated these phenomena. CONCLUSIONS: Our results indicate that PGAM5 can promote necroptosis in trophoblast cells through, at least in part, activation of Drp1. It may be used as a new therapeutic target to prevent trophoblast dysfunction in preeclampsia.

The Preventive Effects of Quercetin on Preterm Birth Based on Network Pharmacology and Bioinformatics.

Our previous study has shown that quercetin prevented lipopolysaccharide-induced preterm birth. This study aims to clarify the potential targets and biological mechanisms of quercetin in preventing preterm birth. We used bioinformatics databases to collect the candidate targets for quercetin and preterm birth. The biological functions and enriched pathways of the intersecting targets were analyzed by gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. Then, the hub targets were identified by cytoscape plugin cytoHubba from the protein-protein interaction network. We obtained 105 targets for quercetin in preventing preterm birth. The biological processes of the intersecting targets are mainly involved in steroid metabolic process, drug metabolic process, oxidation-reduction process, omega-hydroxylase P450 pathway, positive regulation of cell migration, negative regulation of apoptotic process, and positive regulation of cell proliferation. The highly enriched pathways were steroid hormone biosynthesis, metabolism of xenobiotics by cytochrome P450, proteoglycans in cancer, focal adhesion, and arachidonic acid metabolism. The ten hub targets for quercetin in preventing preterm birth were AKT serine/threonine kinase 1, mitogen-activated protein kinase 3, epidermal growth factor receptor, prostaglandin-endoperoxide synthase 2, mitogen-activated protein kinase 1, estrogen receptor 1, heat shock protein 90 alpha family class A member 1, mitogen-activated protein kinase 8, androgen receptor, and matrix metallopeptidase 9. Molecular docking analysis showed good bindings between these proteins and quercetin. In conclusion, these findings highlight the key targets and molecular mechanisms of quercetin in preventing preterm birth.

Neuromedin B mediates IL-6 and COX-2 expression through NF-κB/P65 and AP-1/C-JUN activation in human primary myometrial cells.

Neuromedin B (NMB) and its receptor regulate labor onset by mediating inflammatory factors; however the underlying mechanisms remain poorly understood. The present study is aimed to investigate the mechanisms of NMB-induced cyclo-oxygenase 2 (COX-2) expression and interleukin (IL)-6 generation in human primary myometrial cells. The results indicated that NMB could increase phosphorylation of nuclear factor κB (NF-κB) transcription factor p65 (p65) and Jun proto-oncogene, activator protein 1 (AP-1) transcription factor subunit (c-Jun), and in turn, markedly up-regulated the expression levels of COX-2 and IL-6. This up-regulation was significantly attenuated by knockdown of p65 or c-Jun, and enhanced by overexpression of p65 or c-Jun. Furthermore, we identified a potential interaction between p65 and c-Jun following NMB stimulation. In addition, a significant positive correlation was observed between the amount of phosphorylated p65 and the levels of COX-2 and IL-6, and between the amount of phosphorylated c-Jun and COX-2 and IL-6 levels. These data suggested that NMB-induced COX-2 and IL-6 expression were mediated via p65 and c-Jun activation.

Interaction between NF-κB and AP-1 and their intracellular localization at labor in human late pregnant myometrial cells in vivo and in vitro.

Preterm birth (PTB) is the most important cause of neonatal morbidity and mortality next to congenital anomalies in the developed world. NF-κB and AP-1 were reported to play an important role in parturition initiation. However, the interaction relationship between the 2 molecules in labor initiation has not yet been reported.This study aimed to investigate the interaction between NF-κB and AP-1 and their intracellular translocation during labor in human late pregnant myometrial cells (HLPMCs).Co-immunoprecipitation (Co-IP), Western blot analysis, immunohistochemistry (IHC), and immunocytofluorescence (ICF) techniques were applied to explore the interaction between NF-κB and AP-1 and the alteration in their intracellular localization before and after labor onset.The protein expression levels of NF-κBp65 and AP-1(c-jun) in the natural labor group were observed significantly higher than that in the non-labor group. Pearson's correlation analysis showed a positive correlation between the protein expression of NF-κBp65 and AP-1(c-jun). Interactions were found between the 2 molecules in HLPMCs both in natural labor and non-labor group and were also found in primary culture HLPMCs before and after neuromedin B (NMB) stimulation. NF-κBp65 and AP-1(c-jun) were localized mainly in the cytoplasm before labor onset or NMB stimulation and were translocated into the nucleus upon labor initiation and NMB stimulation.These results demonstrated that upregulated protein expression of NF-κBp65 and AP-1(c-jun), the enhanced interaction between the 2 molecules, and their translocation to nucleus might be correlated to labor initiation.

[Identification of interacting proteins with NF-κB in different status of uterine smooth muscle in labor].

OBJECTIVE: To analyze the differentially expressed proteins which interacted with NF-kappaB in the uterine lower segment smooth muscle tissues under different status of labor onset, and to provide a new foundation on the mechanisms for labor onset.
 Methods: NF-κB P65 protein expression in smooth muscle tissues from the term non-labor group, natural term labor group and drug-induced term labor group was analyzed by Western blot. Co-immunoprecipitation and SDS-PAGE (sodium dodecyl sulfate polyacrylamide gel electrophoresis) were performed to detect the proteins interacting with NF-κB p65 in the NF-κB p65 complexes. The components of the complex were identified by LC-ESI-MS/MS (liquid chromatography-tandem electrospray mass spectrometry) and database analysis. The identified differentially expressed proteins were confirmed by Western blot.
 Results: Positive expression of NF-κB was detected in all of the three groups. 10 differentially expressed proteins were identified by LC-ESI-MS/MS in human lower segment myometrium tissues in the term non-labor group and natural term labor group, mean while, 5 differentially expressed proteins were identified in the term non-labor group and the drug-induced labor group. 3 differential expression proteins were detected in all of the 3 groups, including Heat shock 70, Annexin A6 and Desmin, which were verified by Western blot. These proteins were mainly involved in chaperone, signal transduction, cell structure, and energy metabolism process, respectively.
 Conclusion: NF-κB expressed in uterine smooth muscle cells is involved in the process of initiation and regulation of labor onset through a number of proteins relevant to signal transduction, cell structure and energy metabolism.

[Screening time and schedule for outpatients with acute fatty liver of pregnancy].

OBJECTIVE: To identify the screening time and prepare a screening schedule for outpatients with acute fatty liver of pregnancy (AFLP).
 METHODS: AFLP patients who admitted to Xiangya Hospital and the Second Xiangya Hospital, Central South University, Hunan, China between November, 2006 and December, 2013, were retrospectively studied. The diagnosis of 78 AFLP patients met the domestic clinical and laboratory criteria and the Swansea criteria. Clinical and laboratory data obtained on admission were used for analysis. Contrastive analysis was conducted within our data and other large medical centers or general hospitals. 
 RESULTS: The difference between domestic clinical and laboratory criteria and Swansea criteria in diagnosing AFLP patients in the 2 hospitals mentioned above was significant (P<0.05). The maternal mortality was 14.10% (11/78) and perinatal mortality was 17.95 % (14/78). The mean gestational age at delivery was 35.6 weeks. Based on the clinical and laboratory data, more than 85% of AFLP patients showed abnormal levels of transaminase, bilirubin, and white blood cells, as well as coagulation dysfunction. Gastrointestinal symptoms, such as abdominal pain and vomiting, jaundice, renal impairment and ascites or bright liver on ultrasound scan, were showed in 50%-85% of AFLP patients. Less than 50% of patients suffered from low blood sugar, high blood ammonia or hepatic encephalopathy.
 CONCLUSION: The 34th gestation week might be important time for screening AFLP outpatients. Gastrointestinal symptoms, blood routine, liver function, and coagulant function tests are recommended as the first grade screening indicators. Renal function, blood sugar test, and abdominal ultrasound could be the second grade screening indicators for AFLP outpatients.