Huc-MSC-derived exosomal miR-144 alleviates inflammation in LPS-induced preeclampsia-like pregnant rats via the FosB/Flt-1 pathway.

Background: Preeclampsia (PE) is a common and severe hypertensive disorder in pregnancy. Mesenchymal stem cell-derived exosomes (Exos-MSC) have been reported to mitigate the progression of inflammatory diseases. The study aimed to explore the effects of human umbilical cord-derived Exos-MSC (huc-Exos-MSC) on PE-like models. Methods: Lipopolysaccharide (LPS) was used to construct in vitro and in vivo PE-like models. Exosomes were treated with LPS-induced PE-like cells and rats. Results: PE-like inflammatory models of pregnant rats and cells were successfully constructed in vivo and in vitro. miR-144 was screened by bioinformatics analysis. Exosomes were successfully extracted. Silencing FosB, overexpressing miR-144 or treating with exosomes extracted from huc-MSC overexpressing miR-144 in (Exos-MSCmiR-144) reversed the LPS-induced decline in HTR-8/SVneo cell viability and migration. In addition, the above groups decreased LPS-induced increases in interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), phosphorylated nuclear factor-kappaB (p-NF-κB)/NF-κB, soluble FMS-like tyrosine kinase 1 (sFlt-1), and Flt-1 levels. Simultaneously, transfection of miR-144 mimics and overexpressing FosB reversed those changes in the miR-144 mimics group. miR-144 might alleviate LPS-induced HTR-8/SVneo cell inflammation by targeting FosB. Injection of Exos-MSCmiR-144 in PE-like pregnant rats reversed LPS-induced increases in FosB expression, systolic and diastolic blood pressure (SBP and DBP), as well as mean arterial pressure (MAP), heart rate, urine albumin/creatine ratio, inflammatory factors, p-NF-κB/NF-κB, and sFlt-1 levels. Furthermore, compared with the model group, the proportion of live births was significantly higher in the model + Exos-MSCmiR-144 group, while the apoptosis rate of fetal rat brain tissue was significantly lower. Conclusions: We found that huc-Exos-MSC-derived miR-144 alleviated gestational hypertension and inflammation in PE-like pregnant rats by regulating the FosB/Flt-1 pathway. In addition, huc-Exos-MSC-derived miR-144 could partially reverse the LPS-induced adverse pregnancy outcome and brain injury in fetal rats, laying the foundation for developing new treatments for PE.

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.

3D Printing and Its Current Status of Application in Obstetrics and Gynecological Diseases.

3D printing technology is a novel method of utilizing computer-generated three-dimensional models for drawing, assembling special bioinks, and manufacturing artificial organs and biomedical products. In recent years, it has evolved into a relatively mature therapeutic approach and has been widely used in clinical and basic research. In the field of obstetrics and gynecology, 3D printing technology has been applied for various purposes, including disease diagnosis, treatment, pathogenesis research, and medical education. Notably, researchers have gained significant application experience in common gynecological and obstetrical disorders, such as intrauterine adhesions, uterine tumors, congenital malformations, and fetal congenital abnormalities. This review aims to provide a systematical summary of current research on the application of 3D bioprinting technology in the field of obstetrics and gynecology.

Intrauterine infusion of clinically graded human umbilical cord-derived mesenchymal stem cells for the treatment of poor healing after uterine injury: a phase I clinical trial.

BACKGROUND: Intrauterine adhesion and cesarean scar diverticulum are the main complications of poor healing after uterine injury. Human umbilical cord MSCs transplantation has been regarded as the most potential treatment in the clinic, the safety and efficacy of which in the clinic, however, remains unclear. METHODS: In this study, ten patients were enrolled: six with intrauterine adhesion and four with cesarean scar diverticulum. All the patients were injected with human umbilical cord MSCs twice into the uterus. Beside the chest X-ray, ECG and abdominal ultrasound, many laboratory tests including blood routine, liver and renal function, ovarian function, tumor biomarkers, and immune function were used to estimate the safe after stem cell transplanted. In addition, the efficacy of stem cell transplanted was shown by the endometrial thickness, the volume of the uterus, and cesarean scar diverticulum based on 3D ultrasound imaging. RESULTS: We found that all results of these laboratory tests were normal in these enrolled patients before and after cell injection. Meanwhile, the results of the chest X-ray and ECG were also normal in the treatment process. The abdominal ultrasound showed that the size of the left and right kidneys was inconsistent in one patient after cell therapy, while those of other patients were normal. In addition, endometrial thickness, the volume of the uterus, and cesarean scar diverticulum showed an improving tendency, but no significant difference was noted. CONCLUSION: In summary, intrauterine injection of clinically graded human umbilical cord MSCs was safe for poor healing after uterus injury. Trial registration NCT03386708. Registered 27 December 2017, https://clinicaltrials.gov/ct2/show/NCT03386708?cond=CSD&cntry=CN&draw=2&rank=2.

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.

Maternal outcomes of abnormally invasive placenta in China and their association with use of abdominal aortic balloon occlusion.

OBJECTIVE: To compare maternal outcomes of abnormally invasive placenta in China in 2012, 2015, and 2018, and further examine the association between use of abdominal aortic balloon occlusion (AABO) and the risk of maternal outcomes. MATERIALS AND METHODS: A retrospective analysis included 830 women diagnosed as abnormally invasive placenta from 5 tertiary care centers in China in 2012, 2015 and 2018. Participants were divided into AABO group and non-AABO group according to whether they were treated with AABO or not. Logistic regression models were used to assess the association of use of AABO with postpartum hemorrhage, blood transfusion, hysterectomy and repeated surgery. RESULTS: Among 830 participants, 66.0% (548/830) and 34.0% (282/830) of women were diagnosed with placenta increta and percreta, respectively; 33.3% (276/830) of women with abnormally invasive placenta were treated with AABO. In 2012, 2015, and 2018, the rate of blood transfusion was 83.1, 59.8, and 56.2%; the rate of hysterectomy was 50.8, 11.2, and 2.4%; and the rate of repeated surgery was 10.2, 9.4, and 0.9%. Use of AABO was associated with lower risk of postpartum hemorrhage (OR = 0.59, 95% CI: 0.35-0.99), blood transfusion (OR = 0.72, 95% CI: 0.52-0.99), hysterectomy (OR = 0.04, 95% CI: 0.01-0.14) and repeated surgery (OR = 0.14, 95% CI: 0.05-0.41) after adjustment for potential confounders. CONCLUSION: The rates of blood transfusion, hysterectomy and repeated surgery progressively decreased from 2012 to 2018 in Chinese women with abnormally invasive placenta. Use of AABO was associated with lower risk of postpartum hemorrhage, blood transfusion, hysterectomy and repeated surgery.

Intra-abdominal aortic balloon occlusion in the management of placenta percreta.

BACKGROUND: Massive bleeding is the main concern for the management of placenta percreta (PP). Intra-abdominal aortic balloon occlusion (IABO) is one method for pelvic devascularization, but the efficacy of IABO is uncertain. This study aims to investigate the outcomes of IABO in PP patients. METHODS: We retrospectively reviewed the clinical data of PP cases from six tertiary centers in China between January 2011 and December 2015. PP cases with/without the use of IABO were analyzed. Propensity score matching analysis was performed to reduce the effect of selection bias. Postpartum hemorrhage (PPH) and the rate of hysterectomy, as well as neonatal outcomes, were analyzed. RESULTS: One hundred and thirty-two matched pairs of patients were included in the final analysis. Compared with the control group, maternal outcomes, including PPH (68.9% vs. 87.9%, χ2 = 13.984, P < 0.001), hysterectomy (8.3% vs. 65.2%, χ2 = 91.672, P < 0.001), and repeated surgery (1.5% vs. 12.1%, χ2 = 11.686, P = 0.001) were significantly reduced in the IABO group. For neonatal outcomes, Apgar scores at 1 minute (8.67 ±â€Š1.79 vs. 8.53 ±â€Š1.68, t = -0.638, P = 0.947) and 5 minutes (9.43 ±â€Š1.55 vs. 9.53 ±â€Š1.26, t = 0.566, P = 0.293) were not significantly different between the two groups. CONCLUSIONS: IABO can significantly reduce blood loss, hysterectomies, and repeated surgeries. This procedure has not shown harmful effects on neonatal outcomes.

Conservative management versus cesarean hysterectomy in patients with placenta increta or percreta.

OBJECTIVE: To compare conservative management and cesarean hysterectomy in patients with placenta increta or percreta. MATERIALS AND METHODS: In this multicenter retrospective study, we recorded data on 2219 patients with placenta increta or percreta from 20 tertiary care centers in China from 1 January 2011 to 31 December 2015. Propensity score analysis was used to control for baseline characteristics. We divided patients into conservative management (C) and hysterectomy (H) groups. The primary outcome was operative/postoperative maternal morbidity; secondary outcomes were maternal-neonatal outcomes. RESULTS: In total, 17.9% (398/2219) of patients had placenta increta and percreta; 82.1% (1821/2219) of the patients were in group C. After propensity score matching, 140 pairs of patients from the two groups underwent one-to-one matching. Group C showed less average blood loss within 24 h of surgery (1518 ± 1275 vs. 4309 ± 2550 ml in group H, p<.001). There were more patients with blood loss >1000 ml in group H than in group C (93.6% [131/140] vs. 61.4% [86/140], p<.001). More patients received blood transfusions in group H than in group C (p=.014). There was no significant difference between the groups in terms of bladder injury, postoperative anemia, fever, and disseminated intravascular coagulation. Neonatal outcomes in the two groups were similar. CONCLUSION: Either conservative management or hysterectomy should be considered after thorough evaluation and detailed discussion of risks and benefits. A balance between bleeding control and fertility can be achieved.

The preventive effects of aspirin on preeclampsia based on network pharmacology and bioinformatics.

This study aimed to reveal the key targets and molecular mechanisms of aspirin in preventing preeclampsia. We used bioinformatics databases to collect the candidate targets for aspirin and preeclampsia. The biological functions and signaling pathways of the intersecting targets were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Then, the hub targets were identified by cytoscape plugin cytoHubba from the protein-protein interaction network. We collected 90 targets for aspirin in preventing preeclampsia. The biological processes of the intersecting targets are mainly involved in xenobiotic metabolic process, inflammatory response, negative regulation of apoptotic process, and protein phosphorylation. The highly enriched pathways were FoxO signaling pathway, circadian rhythm, insulin resistance, arachidonic acid metabolism, and drug metabolism-cytochrome P450. The hub targets for aspirin in preventing preeclampsia were tumor protein p53 (TP53), C-X-C motif chemokine ligand 8 (CXCL8), mitogen-activated protein kinase 3 (MAPK3), mitogen-activated protein kinase 1 (MAPK1), mitogen-activated protein kinase 14 (MAPK14), epidermal growth factor receptor (EGFR), estrogen receptor (ESR1), and prostaglandin-endoperoxide synthase 2 (PTGS2). Molecular docking results showed good bindings between the proteins and aspirin. In conclusion, these findings highlight the key targets and molecular mechanisms of aspirin in preventing 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.

Placenta Accreta Spectrum Outcomes Using Tourniquet and Forceps for Vascular Control.

Objective: To evaluate the use of tourniquet and forceps to reduce bleeding during surgical treatment of severe placenta accreta spectrum (placenta increta and placenta percreta). Methods: A tourniquet was used in the lower part of the uterus during surgical treatment of severe placenta accreta spectrum. Severe placenta accreta spectrum was classified into two types according to the relative position of the placenta and tourniquet during surgery: upper-tourniquet type, in which the entire placenta was above the tourniquet, and lower-tourniquet type, in which part or all of the placenta was below the tourniquet. The surgical effects of the two types were retrospectively compared. We then added forceps to the lower-tourniquet group to achieve further bleeding reduction. Finally, the surgical effects of the two types were prospectively compared. Results: During the retrospective phase, patients in the lower-tourniquet group experienced more severe symptoms than did patients in the upper-tourniquet group, based on mean intraoperative blood loss (upper-tourniquet group 787.5 ml, lower-tourniquet group 1434.4 ml) intensive care unit admission rate (upper-tourniquet group 1.0%, lower-tourniquet group 33.3%), and length of hospital stay (upper-tourniquet group 10.2d, lower-tourniquet group 12.1d). During the prospective phase, after introduction of the revised surgical method involving forceps (in the lower-tourniquet group), the lower-tourniquet group exhibited improvements in the above indicators (intraoperative average blood loss 722.9 ml, intensive care unit admission rate 4.3%, hospital stays 9.0d). No increase in the rate of complications was observed. Conclusion: The relative positions of the placenta and tourniquet may influence the perioperative risk of severe placenta accreta spectrum. The method using a tourniquet (and forceps if necessary) can improve the surgical effect in cases of severe placenta accreta spectrum.

Neuromedin B receptor mediates neuromedin B-induced COX-2 and IL-6 expression in human primary myometrial cells.

The precise mechanisms that lead to parturition remain unclear. In our initial complementary DNA (cDNA) microarray experiment, we found that the neuromedin B receptor (NMBR) was differentially expressed in the human myometrium during spontaneous or oxytocin-induced labor. We have previously shown that neuromedin B (NMB) could induce interleukin 6 (IL-6) and type 2 cyclo-oxygenase enzyme (COX-2) expression in the primary human myometrial cells via nuclear factor kappa B (NF-κB) transcription factor p65 (p65) and Jun proto-oncogene, activator protein 1 (AP-1) transcription factor subunit (c-Jun). This study is aimed to investigate whether NMBR is required for NMB-induced effect. Primary myometrial cell culture was established to provide a suitable model to investigate the mechanism of NMB in labor initiation. Immunochemical staining was conducted to validate the NMBR expression in primary myometrial cells. The mRNA and protein expression of NMBR, p65, c-Jun, COX-2 and IL-6 were assessed by Quantitative Real Time PCR (RT-qPCR) and western blotting. Lentiviruses with shRNAs targeting NMBR or containing cDNA sequence of NMBR were transfected to primary myometrial cells to knockdown or overexpress NMBR. Cell death was determined by annexin V and propidium iodide staining and analyzed by flow cytometry. The upregulation of COX-2 and IL-6 and phosphorylation of p65 and c-Jun were significantly attenuated by knockdown of NMBR and enhanced by overexpressed NMBR following NMB treatment, with no significant change in total p65 and c-Jun. In summary, this study showed that NMBR-mediated NMB-induced NF-κB and AP-1 activation, which in turn, induce expression of IL-6 and COX-2 in primary myometrial cells.

Gli2 mediates the development of castration­resistant prostate cancer.

Glioma­associated oncogene family zinc finger 2 (Gli2), a key component of the hedgehog signaling pathway, has been previously demonstrated to promote the malignant properties of prostate cancer in vitro. However, the role of Gli2 in the development of castration­resistant prostate cancer (CRPC) has yet to be fully elucidated. In the present study, Gli2 expression was knocked down in androgen­responsive prostate cancer cells using an inducible Gli2 short hairpin RNA. Suppression of Gli2 expression resulted in significant reduction of cell viability, increased the proportion of cells in the G0/G1 phases of the cell cycle and reduced the expression of genes associated with cell cycle progression. Gli2 knockdown sensitized both androgen­dependent and ­independent prostate cancer cells to the antiandrogen drug Casodex and prevented the outgrowth of LNCaP prostate cancer cells. In addition, Gli2 knockdown significantly suppressed the development of CRPC in a LNCaP xenograft mouse model, which was reversed by the re­expression of Gli2. In conclusion, to the best of our knowledge, the present study was the first occasion in which the essential role of Gli2 in the development of CRPC was demonstrated, providing a potential therapeutic target for the intervention of CRPC.

Combined effects of ambient air pollution and home environmental factors on low birth weight.

BACKGROUND: Low birth weight (LBW) remains a major public health problem worldwide, yet its crucial environmental risk factors are still unclear. OBJECTIVE: To examine the association between LBW (term and preterm LBW) and prenatal exposure to ambient air pollution and home environmental factors as well as their combination, in order to identify critical time window for exposure and key outdoor and indoor factors in LBW development. METHODS: A cohort study of 3509 preschool children was performed in Changsha, China during the period 2011-2012. A questionnaire was conducted to survey each child's birth outcome and each mother's exposure to home environmental factors including parental smoking, new furniture, redecoration, mold/damp stains, window pane condensation, and household pets during pregnancy. Maternal exposure to inhalable particulate matter (PM10), industrial air pollutant (SO2), and traffic air pollutant (NO2) was estimated during different time windows of gestation, including conception month, three trimesters, birth month, and whole gestation. Associations of term and preterm LBW with ambient air pollutants and home environmental factors were assessed by multiple logistic regression models in terms of odds ratio (OR) with 95% confidence interval (CI). RESULTS: Term LBW (TLBW) was significantly associated with exposure to ambient PM10 during pregnancy, with OR (95% CI) = 1.47 (1.00-2.14) for per IQR increase after adjustment for the covariates and home environmental factors. Specifically, we identified the significant association in early phase of pregnancy including conception month (1.90, 1.09-3.30) and the first trimester (1.72, 1.10-2.69). We further found that TLBW was significantly related with parental smoking at home, OR (95% CI) = 2.17 (1.09-4.33). However, no association was observed for preterm LBW (PLBW). The TLBW risk of ambient air pollution and home environmental factors was independent each other and hence the combined exposure to ambient PM10 and indoor parental smoking caused the highest risk. Sensitivity analysis suggested that foetus with younger mothers were significantly more susceptible to risk of indoor parental smoking, while those with smaller house and cockroaches were more sensitive to risk of outdoor PM10 exposure. CONCLUSION: Prenatal exposure to combined outdoor and indoor air pollution, particularly in critical window(s) during early pregnancy, significantly increases the risk of term LBW.

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.

A new method for selective reduction in TRAP sequence with a contraindication to fetoscopic surgery: A case report.

RATIONALE: The preferred method for multifetal pregnancy reduction (MFPR) is a transabdominal intrathoracic or intracranial injection of potassium chloride (KCl). However, in monochorionic multiple pregnancies (MMPs), especially in monoamnionic multifetal pregnancies, selective feticide by this method is often associated with miscarriage of the remaining fetuses. Selective fetal reduction in MMPs by blood flow ablation using radiofrequency ablation or fetoscopic laser surgery may improve survival of the remaining fetus. Although often successful, MFPR by these methods is contraindicated in cases of twin reversed arterial perfusion (TRAP) sequence in triplet pregnancies complicated by polyhydramnios or anterior placenta, as it is difficult to locate the ablation target. PATIENT CONCERNS: 2 cases were admitted to Xiangya Hospital, Central South University with triplet pregnancies at 23 or 21weeks of gestation. DIAGNOSES: Case 1 was a 29-year-old woman with a triplet pregnancy in 2 distinct amniotic sacs and 1 fetus with multiple malformations. Case 2 was a 32-year-old woman who was identified as a triplet pregnancy with TRAP sequence with an acardiac/acephalic twin and anterior placenta. INTERVENTIONS: Both of the 2 cases were underwent a new method for MFPR involving fine needle amniotic fluid aspiration and injection of hypertonic sodium chloride (10% NaCl) into the Wharton jelly of the umbilical cord. OUTCOMES: The 2 cases resulted in selective feticide and the birth of the remaining infants from the triplet pregnancies. All infants were healthy at birth and the 2-year follow-up. LESSONS: The new approach provided a safer, more accessible, and more cost-effective method for MFPR in MMPs with a contraindication to fetoscopic surgery compared to radiofrequency ablation and fetoscopic laser surgery.

[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.