Immunological parameters of maternal peripheral blood as predictors of future pregnancy outcomes in patients with unexplained recurrent pregnancy loss.

INTRODUCTION: Unexplained recurrent pregnancy loss (URPL), affecting approximately 1%-5% of women, exhibits a strong association with various maternal factors, particularly immune disorders. However, accurately predicting pregnancy outcomes based on the complex interactions and synergistic effects of various immune parameters without an automated algorithm remains challenging. MATERIAL AND METHODS: In this historical cohort study, we analyzed the medical records of URPL patients treated at Xiangya Hospital, Changsha, China, between January 2020 and October 2022. The primary outcomes included clinical pregnancy and miscarriage. Predictors included complement, autoantibodies, peripheral lymphocytes, immunoglobulins, thromboelastography findings, and serum lipids. Least absolute shrinkage and selection operator (LASSO) analysis and logistic regression analysis was performed for model development. The model's performance, discriminatory, and clinical applicability were assessed using area under the curve (AUC), calibration curve, and decision curve analysis, respectively. Additionally, models were visualized by constructing dynamic and static nomograms. RESULTS: In total, 502 patients with URPL were enrolled, of whom 291 (58%) achieved clinical pregnancy and 211 (42%) experienced miscarriage. Notable differences in complement, peripheral lymphocytes, and serum lipids were observed between the two outcome groups. Moreover, URPL patients with elevated peripheral NK cells (absolute counts and proportion), decreased complement levels, and dyslipidemia demonstrated a significantly increased risk of miscarriage. Four models were developed in this study, of which Model 2 demonstrated superior performance with only seven predictors, achieving an AUC of 0.96 (95% CI: 0.93-0.99) and an accuracy of 0.92. A web-based platform was established to visually present model 2 and to facilitate its utilization by clinicians in outpatient settings (available from: https://yingrongli.shinyapps.io/liyingrong/). CONCLUSIONS: Our findings suggest that the implementation of such prediction models could serve as valuable tools for providing comprehensive information and facilitating clinicians in their decision-making processes.

Expression of LncRNA KCNQ1Ot1 in diabetic nephropathy and its correlation with MEK/ERK signaling pathway.

OBJECTIVE: To explore the expression of LncRNA KCNQ1OT1 in diabetic nephropathy (DN), and its correlation with MEK/ERK signaling pathway. METHODS: 148 patients with type 2 diabetes in our hospital were selected as research subjects, including 83 patients with simple type 2 diabetes (T2D group) and 65 patients with type 2 diabetes with DN (DN group). Another 50 non-diabetic patients were enrolled as the control group. The expressions of LncRNA KCNQ1OT1 and MEK/ERK signaling pathway related molecules in peripheral blood mononuclear cells (PBMCs) of the three groups of subjects were detected and their correlations were analyzed. In addition, 30 Wistar rats were divided into a control group, diabetes group and DN model group, and the expression of LncRNA KCNQ1OT1 and MEK/ERK signal pathway-related molecules in kidney tissue of the three groups was detected and compared. RESULTS: The relative expression of LncRNA KCNQ1OT1, MEK-5 and ERK2 in the control group was lower than that of the T2D group and DN group (P<0.05), and the relative expression of LncRNA KCNQ1OT1 in T2D group was lower than that of DN group (P<0.05). The expression of LncRNA KCNQ1OT1 was positively-correlated with MEK-5 and ERK2 (P<0.05). The relative expression of LncRNA KCNQ1OT1, MEK-5, and ERK2 in renal tissues of the DN group was higher than those in the control group and diabetes group (P<0.05). CONCLUSION: The expression of LncRNA KCNQ1OT1 in PBMCs of DN patients is abnormally increased, and may be a biomarker for the diagnosis and treatment of the disease. In addition, an abnormal increase of LncRNA KCNQ1OT1 is associated with the activation of the MEK/ERK signaling pathway.

Effects of liraglutide on lipolysis and the AC3/PKA/HSL pathway.

BACKGROUND: Liraglutide reduces blood glucose, body weight and blood lipid levels. Hormone-sensitive lipase (HSL) is a key enzyme in lipolysis. Evidence from our and other studies have demonstrated that adenylate cyclase 3 (AC3) is associated with obesity and can be upregulated by liraglutide in obese mice. In the present study, we investigated whether hepatic HSL activity is regulated by liraglutide and characterized the effect of liraglutide in the AC3/protein kinase A (PKA)/HSL signalling pathway. METHODS: Obese mice or their lean littermates were treated with liraglutide or saline for 8 weeks. Serum was collected for the measurement of insulin and lipids. We investigated hepatic AC3, HSL and phosphorylated HSL Ser-660 (p-HSL(S660)) protein expression levels andAC3 and HSL mRNA expression levels and cyclic adenosine monophosphate (cAMP), PKA activity in liver tissue. RESULTS: Liraglutide treatment decreased triglycerides (TGs) and free fatty acids (FFAs), increased glycerol, and upregulated hepatic AC3 and p-HSL(s660) levels and cAMP and PKA activities. CONCLUSION: The results suggest that liraglutide can upregulates AC3/PKA/HSL pathway and may promotes lipolysis.