[Correlation between endogenous EPO levels and electrocardiogram scatter plot changes in patients with coronary heart disease and autonomic nerve function injury].

Objective: To analyze the correlation between endogenous EPO levels and electrocardiogram scatter plot changes in patients with coronary heart disease and autonomic nerve function injury. Methods: Forty-eight patients who underwent coronary arteriography (CAG) inspection due to chronic coronary heart diseases were selected from July 2015 to October 2015. All of them were evaluated by the Ewing standard autonomic nervous function test, and were divided into Ewing(+) group and Ewing(-) group according to the results of the test. The clinical data of the patients was collected and venous blood was extracted to detect EPO level. Results: The EPO level of Ewing (+) group ((13±3) mIU/ml) was significantly higher than that of Ewing (-) group ((10±3) mIU/ml). The Lorenz scatter plot comet shapes between the two groups had a significant difference. As for the quantitative indicators of Lorenz scatterplot, length of the Ewing (+) group ((147±22) ms) was shorter than that of the Ewing (-) group ((164±24) ms) and there was no significant differences in the width between the two groups. EPO level was negatively correlated with length in both groups (r=-0.427, P=0.002), but not with width (r=0.091, P=0.539). Binary logistic regression analysis showed that EPO (OR=1.394) and diastolic blood pressure (OR=1.091) were risk factors for autonomic nervous function damage. Length (OR=0.934) was a protective factor for autonomic nervous function. ROC curve analysis showed that the area under the EPO curve was 0.737 and that under the length curve was 0.719. Conclusions: The endogenous EPO levels are associated with the changes of electrocardiogram scatter plot in patients with coronary heart disease and autonomic nerve function injury. EPO and length of scatter plot have the similar diagnostic value on predicting of autonomic nerve function injury.

[Clinicopathologic study of pediatric vascular anomalies: a report of 117 cases].

OBJECTIVE: To study the clinicopathologic features of pediatric vascular anomalies and application of ISSVA classification. METHODS: The clinical features, histopathologic findings and immunohistochemical results were analyzed in 117 cases of pediatric vascular anomalies encountered during the period from May 2014 to May 2015. RESULTS: A total of 117 cases of vascular anomalies were studied. The age of patients ranged from 18 hours after birth to 11 years (mean age =34 months and median age =27 months). There were 73 male patients and 44 female patients, with the male-to-female ratio being 1.7∶1.0. Congenital skin lesions were found in 37 cases (31.6%). The common sites of involvement included head and neck region (46 cases, 39.3%), trunk (28 cases, 23.9%), extremities (14 cases, 12.0%) and internal viscera (31 cases, 26.5%). According to the new ISSVA classification, there were 74 cases of vascular malformations and 43 cases of vascular neoplasms (ratio=1.7∶1.0). The commonest vascular tumor encountered was infantile hemangioma (21 cases, 48.8%), including 17 cases in proliferative phase and 4 cases in involutive phase. Thirteen cases (23.3%) of congenital hemangioma were found, with 8 cases of rapidly involuting congenital hemangioma and 5 cases of non-involutive congenital hemangioma. Three of the congenital hemangioma occurred in liver. There were 5 cases (11.6%) of pyogenic granuloma, 3 cases (7.0%) of tufted angioma and 1 case (2.3%) of Kaposiform hemangioendothelioma. Amongst the 74 cases of vascular malformations encountered, lymphatic malformation was found in 47 cases (63.5%), venous malformation in 15 cases (20.2%), lymphatic-venous malformation in 11 cases (14.9%) and arteriovenous malformation in 1 case (1.4%). All cases of vascular anomalies were all positive for CD31 on immunostaining. Glut1 and CD15 were positive both in proliferative and involutive phases of the 21 cases of infantile hemangioma, while other vascular tumors and vascular malformations were negative. Forty-seven cases of lymphatic malformation and 11 cases of lymphatic-venous malformation showed D2-40 expression. Focal positivity for D2-40 was demonstrated in 3 cases of tufted angioma and 1 case of Kaposiform hemangioendothelioma. CONCLUSIONS: Vascular anomalies affecting infants and children include tumors and malformations. Accurate histopathologic diagnosis and ISSVA classification of the various types of vascular anomalies play an important role in clinical management.

c-Met and RON expression levels in endometrial adenocarcinoma tissue and their relationship with prognosis.

OBJECTIVE: To investigate the potential relevance of c-Met and RON gene expression in patients with adenocarcinoma of the endometrium and analyze the relationships among the c-Met and RON expression, clinicopathological characteristics, and patient survival. MATERIALS AND METHODS: The study included 60 cases diagnosed with endometrial adenocarcinoma with more than five-years follow-up. Total RNA from formalin-fixed paraffin-embedded tissues of 60 adenocarcinomas of the endometrium and normal endometrium tissues were isolated for c-Met and RON quantitative analysis by real-time real-time polymerase chain reaction (RT-PCR). RESULTS: The c-Met and RON expression in endometrial adenocarcinoma was significantly higher than that in normal endometrial tissues (p < 0.01), with average up-regulated levels of 3.94 ± 1.88 and 2.74 ± 0.88, respectively. Moreover, high c-Met expression was significantly correlated with the histological stage (p = 0.017), and high RON expression was related to histological stage (p = 0.035), muscle invasion (p = 0.006), and lymph node metastasis (p = 0.018). Multivariate Cox regression analysis revealed that the co-expression of c-Met and RON was an independent prognostic factor for adenocarcinoma of the endometrium and was significantly associated with decreased overall survival (HR = 3.571, p = 0.014). CONCLUSION: The co-expression of c-Met and RON is associated with a poor prognosis in endometrial adenocarcinoma and is an independent prognostic marker for endometrioid adenocarcinoma.

MicroRNA-29b Promotes Subchondral Bone Loss in TMJ Osteoarthritis.

Abnormal subchondral bone remodeling plays important roles during osteoarthritis (OA) pathology. Recent studies show that bone marrow mesenchymal stem cells (BMSCs) in osteoarthritic subchondral bones exhibit a prominent pro-osteoclastic effect that contributes to abnormal subchondral bone remodeling; however, the pathologic mechanism remains unclear. In the present study, we used a mouse model with OA-like change in the temporomandibular joint (TMJ) induced by an experimentally unilateral anterior crossbite (UAC) and found that the level of microRNA-29b (miR-29b), but not miR-29a or miR-29c, was markedly lower in BMSCs from subchondral bones of UAC mice as compared with that from the sham control mice. With an intra-articular aptamer delivery system, BMSC-specific overexpression of miR-29b by aptamer-agomiR-29b rescued subchondral bone loss and osteoclast hyperfunction in UAC mice, as demonstrated by a significant increase in bone mineral density, bone volume fraction, trabecular thickness, and the gene expression of osteocalcin and Runx2 but decreased trabecular separation, osteoclast number and osteoclast surface/bone surface, and the gene expression of cathepsin K, Trap, Wnt5a, Rankl, and Rank as compared with those in the UAC mice treated by aptamer-NC (all P < 0.05). In addition, BMSC-specific inhibition of miR-29b by aptamer-antagomiR-29b exacerbated those responses in UAC mice. Notably, although it primarily affected miR-29b levels in the subchondral bone (but not in cartilage and synovium), BMSC-specific overexpression of miR-29b in UAC mice largely rescued OA-like cartilage degradation, including decreased chondrocyte density, cartilage thickness, and the percentage areas of proteoglycans and type II collagen, while BMSC-specific inhibition of miR-29b aggravated these characteristics of cartilage degradation in UAC mice. Moreover, we identified Wnt5a, but not Rankl or Sdf-1, as the direct target of miR-29b. The results of the present study indicate that miR-29b is a key regulator of the pro-osteoclastic effects of BMSCs in TMJ-OA subchondral bones and plays important roles in the TMJ-OA progression.

Long non-coding RNA LINC00152 is up-regulated in ovarian cancer tissues and regulates proliferation and cell cycle of SKOV3 cells.

OBJECTIVE: To characterize functions of long non-coding RNA (lncRNA) in the progression of epithelial ovarian cancer. PATIENTS AND METHODS: Epithelial ovarian cancer tissues and matching normal tissues were collected from two individual patients for RNA microarray analysis. Besides, twenty-two ovarian cancer samples and ten healthy ovarian epithelial tissues were collected for Reverse Transcription-quantitative Polymerase Chain Reaction (RT-qPCR). Microarray assay suggested that a list of cancer relating mRNAs and lncRNAs were upregulated. The identified lncRNAs were validated via RT-qPCR, which led to the identification of long intergenic non-protein coding RNA 152 (LINC00152). To determine the function of LINC00152 in ovarian cancer, we knocked down the expression of LINC00152 in epithelial ovarian cancer cell line SKOV3 with small interference RNAs (siRNAs). The effects of LIN00152 on the proliferation and cell cycle were determined by comparing the cell viability of SKOV3 cells with LIN00152 knockdown and the control cells with negative siRNA. The cell viability was assessed using Cell Counting Kit-8 (CCK-8) and flow cytometry assay. RNA microarray assay was used again in control and LINC00152 knockdown SKOV3 cells to identify downstream signaling pathways. RESULTS: Fourteen ovarian cancer relating lncRNAs were identified by RNA microarray assay. Up-regulation of LINC00152 was validated via RT-qPCR. A higher expression of LINC00152 in late cancer stage (III-IV) compared to the early stage tumors was also demonstrated. Inhibition of LINC00152 in SKOV3 cells inhibited cell proliferation and induced cell cycle arrest that involved prolonged G1 phase and shortened S phase. The microarray assay data of SKOV3 cells suggested that Cyclin-Dependent Kinase Inhibitor 1C (CDKN1C) was a potential downstream target of LINC00152. CONCLUSIONS: LINC00152 is upregulated in epithelial ovarian cancer tissues comparing to normal tissues. Knockdown of LINC00152 expression inhibits cell proliferation and induces cell cycle arrest. LINC00152 possibly interacts with Tumor Necrosis Factor (TNF) signaling pathway. CDKN1C is a potential downstream target of LINC00152.

Roles of notch signaling pathway and endothelial-mesenchymal transition in vascular endothelial dysfunction and atherosclerosis.

OBJECTIVE: To investigate the role of the Notch signaling pathway on the endothelial-mesenchymal transition (EndMT) during vascular endothelial dysfunction and atherosclerosis. MATERIALS AND METHODS: Human coronary artery endothelial cells (HCAEC) were treated with the exogenous Notch homolog 1 (Notch1) factor to activate the Notch1 pathway, and cells were then observed under the microscope for morphologic changes. Changes in the expression of related proteins were detected by Western blot. In vivo experiments were performed using 18 Sprague Dawley® (SD) rats, and GSI factor was used to specifically inhibit Notch pathway activation. Rats were used and randomly divided into three groups: normal diet (ND) group, high-fat diet (HFD) group, and high-fat diet + GSI (HFD+GSI) group, 6 rats in each group. Hematoxylin and eosin (H&E) staining was used to examine the cardiac aortic morphology of the rats in each treatment group. Real-time polymerase chain reaction (RT-PCR) and Western blot were used to detect the expression of Notch1, Hes1, VE-cadherin and α-SMA in the aortic tissues of rats in each group at mRNA and protein levels, respectively. RESULTS: After HCAECs were treated with Notch1, endothelial protein levels of VE-cadherin were significantly decreased and levels of the interstitial protein α-SMA were significantly increased. In the animal model, the rats fed with high-fat diet for two months presented obvious atherosclerosis spots in their aorta, but those fed with the same diet and treated with GSI inhibitor of Notch pathway showed significantly fewer atherosclerosis signs. Compared with ND group, mRNA and protein expression levels of Notch1, Hes1 and α-SMA were significantly increased, and the expression levels of endothelial marker VE-cadherin were significantly decreased in aortas of rats in HFD group. Compared with the rats in HFD group, the rats in HFD+GSI group showed significantly reduced expression levels of Notch1, Hes1 and α-SMA. CONCLUSIONS: The activation of Notch signaling pathway can induce the EndMT progression and promote the development of atherosclerotic lesions.