A Prediction Model of Preeclampsia in Hyperglycemia Pregnancy.

Purpose: To investigate the risk factors associated with preeclampsia in hyperglycemic pregnancies and develop a predictive model based on routine pregnancy care. Patients and Methods: The retrospective collection of clinical data was performed on 951 pregnant women with hyperglycemia, including those diagnosed with diabetes in pregnancy (DIP) and gestational diabetes mellitus (GDM), who delivered after 34 weeks of gestation at the Maternal and Child Health Hospital Affiliated to Anhui Medical University between January 2017 and December 2019. Observation indicators included liver and kidney function factors testing at 24-29+6 weeks gestation, maternal age, and basal blood pressure. The indicators were screened univariately, and the "rms" package in R language was applied to explore the factors associated with PE in HIP pregnancy by stepwise regression. Multivariable logistic regression analysis was used to develop the prediction model. Based on the above results, a nomogram was constructed to predict the risk of PE occurrence in pregnant women with HIP. Then, the model was evaluated from three aspects: discrimination, calibration, and clinical utility. The internal validation was performed using the bootstrap procedure. Results: Multivariate logistic regression analysis showed that cystatin C, uric acid, glutamyl aminotransferase, blood urea nitrogen, and basal systolic blood pressure as predictors of PE in pregnancy with HIP. The predictive model yielded an area under curve (AUC) value of 0.8031 (95% CI: 0.7383-0.8679), with an optimal threshold of 0.0805, at which point the sensitivity was 0.8307 and specificity of 0.6604. Hosmer-Lemeshow test values were P = 0.3736, Brier score value was 0.0461. After 1000 Bootstrap re-samplings for internal validation, the AUC was 0.7886, the Brier score was 0.0478 and the predicted probability of the calibration curve was similar to the actual probability. A nomogram was constructed based on the above to visualize the model. Conclusion: This study developed a model for predicting PE in pregnant women with HIP, achieving high predictive performance of PE risk through the information of routine pregnancy care.

Pregnancy-Specific Beta-1-Glycoprotein 1 Increases HTR-8/SVneo Cell Migration through the Orai1/Akt Signaling Pathway.

The impaired invasion ability of trophoblast cells is related to the occurrence of preeclampsia (PE). We previously found that pregnancy-specific beta-1-glycoprotein 1 (PSG1) levels were decreased in the serum of individuals with early-onset preeclampsia (EOPE). This study investigated the effect of PSG1 on Orai1-mediated store-operated calcium entry (SOCE) and the Akt signaling pathway in human trophoblast cell migration. An enzyme-linked immunosorbent assay (ELISA) was used to determine the level of PSG1 in the serum of pregnant women with EOPE. The effects of PSG1 on trophoblast proliferation and migration were examined using cell counting kit-8 (CCK8) and wound healing experiments, respectively. The expression levels of Orai1, Akt, and phosphorylated Akt (p-Akt) were determined through Western blotting. The results confirmed that the serum PSG1 levels were lower in EOPE women than in healthy pregnant women. The PSG1 treatment upregulated the protein expression of Orai1 and p-Akt. The selective inhibitor of Orai1 (MRS1845) weakened the migration-promoting effect mediated by PSG1 via suppressing the Akt signaling pathway. Our findings revealed one of the mechanisms possibly involved in EOPE pathophysiology, which was that downregulated PSG1 may reduce the Orai1/Akt signaling pathway, thereby inhibiting trophoblast migration. PSG1 may serve as a potential target for the treatment and diagnosis of EOPE.

Pregnancy-Specific Glycoprotein 9 Enhances Store-Operated Calcium Entry and Nitric Oxide Release in Human Umbilical Vein Endothelial Cells.

We explored changes in pregnancy-specific glycoprotein 9 (PSG9) levels in the serum of patients with preeclampsia and the effects and underlying mechanisms of PSG9 effects on calcium (Ca2+) homeostasis and nitric oxide (NO) release in human umbilical vein endothelial cells (HUVECs). Western blotting was used to detect protein expression levels, and an NO fluorescence probe was used to examine NO production. Intracellular Ca2+ concentrations were measured using a Ca2+-sensitive fluorescent dye under a fluorescence microscope. Compared with those in healthy pregnant women, serum PSG9 levels were significantly decreased in patients with preeclampsia. PSG9 (0.1 µg/mL) treatment of HUVECs significantly enhanced the expression levels of store-operated calcium entry (SOCE) channel proteins Orai1 and Orai2, but not Orai3, and of endothelial nitric oxide synthase (eNOS) and NO production. Pretreatment with an inhibitor of SOCE (BTP2) abolished PSG9-enhanced Orai1, Orai2, and eNOS expression levels and NO production in HUVECs. The mechanisms underlying SOCE that were PSG9 enhanced in HUVECs appear to involve the Ca2+/eNOS/NO signaling pathway. These findings suggest that serum PSG9 levels may be a potential biomarker for monitoring the occurrence or development of preeclampsia in pregnancy and that PSG9 may be a potential therapeutic target for the treatment of preeclampsia.

[Effect of natural killer cell line NK-92 against human ovarian carcinoma cells in vitro and in vivo].

OBJECTIVE: To study the cytotoxic activity of NK-92 cells irradiated against human ovarian cancer. METHODS: NK-92 cells were exposed to different doses of radiation and assayed for proliferation by a standard (3)H-thymidine incorporation assay and cell count by using trypan blue exclusion. The cytotoxic activity of NK-92 cells against targets was measured in a standard (51)Cr-release assay in vitro. The effectiveness of irradiated NK-92 cells on ovarian cancer was compared with the control group of cancers (without injection of irradiated NK-92 cells). RESULTS: (1) In vitro:The proliferation of NK-92 cells was inhibited by radiation of 4, 8 and 16 Gy, respectively. From the (3)H-thymidine incorporation data, irradiation by 4 Gy reduced cell proliferation to 29% of control, while 8 Gy reduced proliferation to 6%. The cytotoxicity of NK-92 cells at 4 Gy 2 days following irradiation was approximately 42%-62% for ovarian cancer cell HO-8910, while it was 33%-58% at 8 Gy. (2) In vivo: Tumor size in treatment group was (0.047 +/- 0.019) cm(3) on day 30 after inoculation, and (0.167 +/- 0.021) cm(3) on day 40 and (0.343 +/- 0.022) cm(3) on day 50, while the sizes were smaller in treatment group (P < 0.01). In addition, the tumor group animals died between 74-82 days after injection of HO-8910 cells, while the treatment group animals were alive over 120 days (P < 0.01). CONCLUSION: Our study indicates that injection of irradiated NK-92 cells may be a potentially effective treatment for human ovarian carcinoma.