Liraglutide alleviates vascular injury in diabetic rabbits with lower limb vascular stenosis through regulation of RCAN1.

OBJECTIVE: The aim of the present study is to explore the possible mechanism that may have ameliorative effect of liraglutide (Lira) on diabetic lower extremity vascular stenosis. MATERIALS AND METHODS: A diabetic rabbit model of lower extremity stenosis was established and treated with Lira. The intimal hyperplasia of the lower extremity and the oxidative stress level of vascular tissue were observed and examined. Vascular smooth muscle cells (VSMCs) induced by high glucose (HG) were treated with Lira, and RCAN1 overexpressing plasmid was constructed to transfect VCMCs. RESULTS: Lira treatment showed its association in significantly improving the hyperplasia of the intima, the level of oxidative stress, and the level of homeostasis model assessment of insulin resistance (HOMA-IR) in rabbits induced by diabetes and lower limb stenosis. In addition, Lira treatment reduced the elevated expression of RCAN1 in vascular tissues induced by diabetes. Not only could Lira treatment inhibit the increase of ROS level, proliferation and migration of VSMCs induced by HG, but reduce the expression of PCNA, MMP-9 and collagen I induced by HG. Overexpression of RCAN1 in VSMCs counteracted the effect of Lira, suggesting that Lira affected the proliferation and migration of VSMCs by regulating RCAN1. CONCLUSIONS: Our findings have important implications for Lira to exert beneficial outcomes in reducing excessive neointimal formation after lower extremity vascular injury in diabetic rabbits via the regulation of RCAN1.

[Role of Claudin-1 on diagnostic cut-off value and multiple tests in patients with papillary thyroid carcinoma].

Objective: To explore the diagnostic cut-off value of Claudin-1 (Cla-1) in papillary thyroid carcinoma (PTC) and the efficacy of the multiple test. Methods: Clinical and pathological data were collected from 295 patients with PTC and 137 patients with benign thyroid lesions (BTL) admitted to two hospitals in Pingdingshan City, Henan Province from January 2015 to June 2020. The expression index of Cla-1, the positive expression rate of high molecular weight cytokeratin (HMW-CK) and the negative expression rate of leukocyte differentiation antigen 56 (CD56) were calculated according to the results of immunohistochemistry. Receiver operating characteristic (ROC) curve was used to determine the cut-off value of Cla-1 for diagnosing PTC. Cla-1+HMW-CK, Cla-1+CD56, HMW-CK+CD56 and Cla-1+HMW-CK+CD56 were tested in series, and the diagnostic efficacy was evaluated by sensitivity, specificity and accuracy. Results: The age of PTC patients M (P25, P75) was 48.0 (41.0, 55.0) years old, among which 230 cases were male (78.0%). The age of BTL patients M (P25, P75) was 53.0 (46.0, 61.0) years old, including 34 males (24.8%). Cla-1 detection was conducted in all PTC and BTL patients, whereas only 198 and 97 cases conducted HMW-CK detection, 242 and 136 cases conducted CD56 detection, respectively. The M (P25, P75) of Cla-1 expression index in PTC was 80.0% (45.0%, 90.0%), which was higher than that in BTL [0.0 (0.0, 2.0%)] (P<0.001). The positive expression rate of HMW-CK was 93.9% (186/198) in PTC, and was negative in all BTL. The negative expression rate of D56 was 89.7% (217/242) in PTC, higher than that of BTL [1.5% (2/136)] (P<0.001). When expression index 19.0% was set as the cut-off value of Cla-1 for diagnosing PTC, the area under the ROC curve (AUC) was the maximum [AUC (95%CI): 0.981 (0.969, 0.994)], and the sensitivity, specificity and accuracy were 92.2% (272/295), 98.5% (135/137) and 94.2% (407/432), respectively. In multiple tests for diagnosis of PTC, the sensitivity ranged from 89.3% to 94.7%, specificity were all 100.0% and accuracy ranged from 93.1% to 96.9%. Conclusion: Cla-1 expression index ≥19.0% could be set as a cut-off value for the diagnosis of PTC and serial test of Cla-1 combined with HMW-CK(CD56) improves diagnostic specificity.

[Quantitative evaluation of intravoxel incoherent motion diffusion-weighted imaging and three-dimensional arterial spin labeling in Ki-67 labeling index and grading of brain gliomas].

Objective: To investigate the value of multiple parameters derived from intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) and three-dimensional arterial spin labeling (3D-ASL) in Ki-67 labeling index (Ki-67 LI) and grading of human brain gliomas. Methods: From December 2015 to May 2018, 45 patients of gliomas confirmed by surgical pathology in Li Huili Hospital, Ningbo Medical Center were divided into low-grade group (20 cases of WHO grade Ⅱ) and high-grade group (12 cases of WHO grade Ⅲ, 13 cases of WHO grade Ⅳ), and the Ki-67 LI of glioma was obtained by immunohistochemistry. All patients, 24 males and 21 females, aged 25-83 years, mean(53±12)years, underwent conventional magnetic resonance imaging (MRI), IVIM-DWI and 3D-ASL before operation, then measured the true water diffusion coefficient (D), microcirculation perfusion coefficient (D(*)), perfusion fraction (f) and cerebral blood flow (CBF) in the tumor solid area and the contralateral normal white matter area. Those parameters and the Ki-67 LI were compared between the low-and high-grade groups with Mann-Whitney U test. Spearman's correlation was used to analyze the correlation between the quantitative parameters and Ki-67 LI. The ROC curve was used to assess the diagnostic efficacy of parameters in the grading assessment of brain gliomas. Results: The D(0.791×10(-3)mm(2)/s) and f (0.261) of the high-grade group were lower than those of the low-grade group, whereas D(*) (4.153×10(-3) mm(2)/s), CBF(102.027 ml·min(-1)·100 g(-1)) and Ki-67 LI (0.25) were higher (P<0.05). There was a moderate negative correlation between D, f and Ki-67 LI(r=-0.513,-0.457, all P<0.05). There was no significant correlation between D(*) and Ki-67 LI (P=0.571). The area under the curve (AUC) for identifying high-and low-grade gliomas by D, D(*), f and CBF values was 0.965, 0.745, 0.842, and 0.830 respectively (all P<0.05). Conclusion: D and f can be used for quantitative prediction of Ki-67 LI. IVIM-DWI and 3D-ASL are helpful in the grading assessment of gliomas, and the diagnostic efficiency of D is the highest.