Application Prospects and Prospect of Metabolomics in the Identification of Sudden Cardiac Death.

ABSTRACT: In cases of sudden death, the prevention of sudden cardiac death and the analysis of the cause of death after sudden cardiac death have always been a difficult problem. Therefore, clinical research and forensic pathological identification of sudden cardiac death are of great significance. In recent years, metabolomics has gradually developed into a popular field of life science research. The detection of "metabolic fingerprints" of biological fluids can provide an important basis for early diagnosis of diseases and the discovery of potential biomarkers. This article reviews the current research status of sudden cardiac death and the research on metabolomics of cardiovascular diseases that is closely related to sudden cardiac death and analyzes the application prospects of metabolomics in the identification of the cause of sudden cardiac death.

[Treatment of complicated intra-articular distal radius fractures with extended flexor carpi radialis approach].

OBJECTIVE: To discuss the effect of treatment of complicated intra-articular distal radius fractures with extended flexor carpi radialis approach. METHODS: A retrospective analysis of 38 cases with fresh complicated intra-articular distal radius fractures treated by using extended flexor carpi radialis approach in our hospital from October 2012 to March 2015, with 25 males and 13 females. The average age was (52.76±8.62) years (32-64 years). The average time to surgery was (5.42±1.91) d (3-10 d), with left wrist 17 cases and right wrist 21 cases. All the patients were with C3 distal radius fractures according to Association for the Study of Internal Fixation (AO/ASIF) classification. The follow-up was conducted 1, 2, 3, 6, and 12 months after operation, including AP and lateral X-ray, wrist extension and flexion, radial deviation and ulnar deviation, forearm pronation and supination, and grip strength. At the end of 6 and 12 months after operation, all the patients were evaluated by using the modified Garland-Werley score and patient rated wrist evaluation (PRWE). RESULTS: All the patients got good bone union, and their follow-up time was more than 12 months. The average follow-up time was (16.37±2.85) months (12-22 months). The score of modified Garland-Werley evaluation 6 months postoperation was 5.37±2.82, excellent and good rate was 84.21%, the score of modified Garland-Werley evaluation 12 months postoperation was 5.03±2.60, excellent and good rate was 86.84%. The score of PRWE 6 months postoperation was 15.82±8.38, the score of PRWE 12 months postoperation was 12.17±7.58. CONCLUSION: The extended flexor carpi radialis approach is effective for the treatment of complicated intra-articular distal radius fractures and can avoid the complications of volar and dorsal combination approach.

MiR-630 inhibits proliferation by targeting CDC7 kinase, but maintains the apoptotic balance by targeting multiple modulators in human lung cancer A549 cells.

MicroRNAome analyses have shown microRNA-630 (miR-630) to be involved in the regulation of apoptosis. However, its apoptotic role is still debated and its participation in DNA replication is unknown. Here, we demonstrate that miR-630 inhibits cell proliferation by targeting cell-cycle kinase 7 (CDC7) kinase, but maintains the apoptotic balance by targeting multiple activators of apoptosis under genotoxic stress. We identified a novel regulatory mechanism of CDC7 gene expression, in which miR-630 downregulated CDC7 expression by recognizing and binding to four binding sites in CDC7 3'-UTR. We found that miR-630 was highly expressed in A549 and NIH3T3 cells where CDC7 was downregulated, but lower in H1299, MCF7, MDA-MB-231, HeLa and 2BS cells where CDC7 was upregulated. Furthermore, the induction of miR-630 occurred commonly in a variety of human cancer and immortalized cells in response to genotoxic agents. Importantly, downregulation of CDC7 by miR-630 was associated with cisplatin (CIS)-induced inhibitory proliferation in A549 cells. Mechanistically, miR-630 exerted its inhibitory proliferation by blocking CDC7-mediated initiation of DNA synthesis and by inducing G1 arrest, but maintains apoptotic balance under CIS exposure. On the one hand, miR-630 promoted apoptosis by downregulation of CDC7; on the other hand, it reduced apoptosis by downregulating several apoptotic modulators such as PARP3, DDIT4, EP300 and EP300 downstream effector p53, thereby maintaining the apoptotic balance. Our data indicate that miR-630 has a bimodal role in the regulation of apoptosis in response to DNA damage. Our data also support the notion that a certain mRNA can be targeted by several miRNAs, and in particular an miRNA may target a set of mRNAs. These data afford a comprehensive view of microRNA-dependent control of gene expression in the regulation of apoptosis under genotoxic stress.

[Inhibition of signal transduction pathways of endothelin-1-induced proliferation of vascular smooth muscle cells by nitric oxide].

The signal transduction pathways of the inhibitory effect of nitric oxide (NO) on endothelin (ET)-induced proliferation of vascular smooth muscle cells (VSMCs) were studied. 3H-thymidine (TdR) incorporation, mitogen-activated protein kinase (MAPK) activity and protein kinase C (PKC) activity of cultured VSMCs of rabbits thoracic aorta were measured in the presence of either NO precursor L-arginine (L-Arg) or NO donor 3-morpholino sydnonimine-hydrochloride (SIN-1), or ET-1 alone or with L-Arg or SIN-1. The results show: (1) ET-1 (10(-8) mol/L) significantly increased VSMCs 3H-TdR incorporation (5 times, P < 0.01), MAPK activity (4 times, P < 0.01) and PKC activity (3 times, P < 0.01), as compared with control. L-Arg or SIN-1 alone was without effect on 3H-TdR incorporation, MAPK activity and PKC activity. (2) When ET-1 and L-Arg (2, 5, 10 mmol/L) were simultaneously administered, 3H-TdR incorporation and activity of both MAPK and PKC were all significantly decreased in comparison with the ET group. (3) When ET-1 + SIN-1 (5, 10, 50 mumol/L), the effects coincide with those of the ET-1 + L-Arg groups. These findings indicate that NO inhibition of the signal transduction pathways of the ET-1-induced proliferation of VSMCs may be mediated by the inhibition of ET-1-induced activation of both PKC and MAPK.