Aberrant activation of the Hedgehog signaling pathway in granulosa cells from patients with polycystic ovary syndrome.

The molecular mechanism that triggers polycystic ovary syndrome (PCOS) is mysterious. Abnormal development of ovarian granulosa cells (GCs) is one of the causes of PCOS. Herein, our study was carried out using RNA-seq to detect the different gene expression levels in ovarian GCs between three patients with PCOS and four normal controls. To verify the RNA-seq data, GCs from 22 patients with PCOS and 21 controls with normal ovulation were collected to perform the RT-PCR analysis. Hedgehog signaling pathway (Hh) members, Ihh and Ptch2 were abnormally highly expressed in the PCOS tissue (PT). The qPCR also indicated that the expression levels of Hh signaling pathway downstream members, Ptch1, Gli1, and Gli2 in the PT were significantly higher than those in the normal tissue (NT). Besides, the expression of TNF-α mRNA in PCOS patients was higher than that in the control group. Through the chromatin immunoprecipitation assay (ChIP), we found that the Gli1-IP-DNA enriched from the granular cells of PCOS patients was higher than that of the control group. Finally, the Hh signaling pathway inhibitor, cyclopamine, can decrease the apoptosis of PCOS ovarian granulosa cells. These results suggest that abnormal activation of Hh signaling pathway, especially Ihh signal, may have a profound influence on PCOS.

The Correlation between Time in Range and Diabetic Microvascular Complications Utilizing Information Management Platform.

BACKGROUND: In recent years, the time of blood glucose within the target range is a new research hotspot in blood glucose management. TIR is expected to be a novel indicator for evaluating the efficacy of glycemic control and predicting diabetic complications. However, its relationship with diabetic complications has not been fully elucidated. OBJECTIVE: To explore the relationship between time in range (TIR) and glycosylated hemoglobin (HbA1C) through the information big data management platform. Possible association between TIR and diabetic microvascular complications (retinopathy, nephropathy, and neuropathy) was investigated, attempting to provide theoretical basis for the clinical application of TIR and to explore the TIR control scope suitable for diabetic patients. METHODS: A total of 5,644 type 2 diabetic patients hospitalized in the Department of Endocrinology, the Second Affiliated Hospital of Nanchang University, were selected from April 2017 to June 2020. Fingertip capillary blood glucose monitoring (FCGM) was monitored for a total of 455,664 times, and patients who are nondiabetic, pregnant, or with diabetic ketosis were excluded. Patients with 7 blood glucose points monitored for at least three consecutive days were selected as subjects in the study. 1,895 males and 1,513 females with diabetes were included, with an average age of (59.74 ± 13.40) years old and an average course of disease of 8.28 ± 7.11 years. The proportion of time in range (TIR) (70∼180 mg/dl) within the target range and the correlation between TIR and HbA1C were analyzed, as well as the relationship between TIR and the risk of diabetic complications. RESULTS: (1) The average of TIR and HbA1C was 49.65 ± 23.36% and 8.92 ± 2.49%, respectively, and was linearly correlated. With the decrease of TIR, HbA1C increased significantly, and the difference was statistically significant (P < 0.01, R 2 = 0.458). The correlation coefficient of mean TIR with mean HbA1C was -0.626. (2) There were 836 patients diagnosed with diabetic nephropathy (DN). The difference of TIR value between DN and non-DN was significant (T = 2.250, P < 0.05). Risk assessment showed the lower the TIR was, the higher the risk of DN was. TIR less than 40% was a risk factor for DN (OR = 1.249, 95% CI: 0.915-1.375). (3) There were 1,296 patients diagnosed with diabetic peripheral neuropathy (DPN). The difference of TIR value between DPN and non-DPN was significant (T = 3.844, P < 0.01). TIR value less than 70% was a risk factor for DPN (OR = 1.030, 95% CI: 0.769-1.379). (4) There were 2,077 patients diagnosed with diabetic retinopathy (DR). The difference of TIR value between DPN and non-DPN was significant (T = 3.608, P < 0.01). TIR value less than 50% was a risk factor for DR (OR = 1.092, 95% CI: 0.898-1.264). Summary. TIR may serve as a reference index for short-term blood glucose control, strongly reflecting the clinical blood glucose regulation and predicting the risk of diabetic microvascular complications.