LncRBA GSA5, up-regulated by ox-LDL, aggravates inflammatory response and MMP expression in THP-1 macrophages by acting like a sponge for miR-221.

Atherosclerosis is a chronic inflammatory process, plaque rupture and subsequent thrombosis underline the major causes of acute cardio-cerebral vascular diseases. Long non-coding RNAs (lncRNAs) participate in diverse pathologic processes, including inflammation and myocardial infarction. Recent study confirmed the elevation of lncRNA growth arrest-specific 5 (GAS5) in atherosclerotic rats. In this study, we aimed to explore the role and mechanism of GAS5 in the progression of atherosclerotic plaque. Here, expression of GAS5 was enriched in atherosclerotic plaques and THP-1 macrophage exposed to oxidized low-density lipoprotein (ox-LDL). Furthermore, overexpression of GAS5 aggravated ox-LDL-induced pro-inflammatory cytokines (IL-6, IL-1ß, TNF-α) and chemokine MCP-1 secretion in macrophages, which were reversed after GAS5 cessation. Additionally, high expression and secretion of MMP-2 and MMP-9 were increased in ox-LDL-stimulated macrophages following GAS5 elevation, but these increases were inhibited in GAS5-silenced group. Mechanism analysis identified GAS5 as a endogenous sponge to directly bind and suppress miR-221 expression. Notably, miR-221 elevation antagonized GAS5-enhanced inflammatory response and MMPs in macrophages upon ox-LDL. These results suggest that GAS5 can trigger inflammatory response and MMP expression by acting as a sponge of miR-221, which may facilitate fibrous cap degradation and aggravate atherosclerotic plaque destabilization, supporting a promising therapeutic agent against atherosclerosis.

Using Entropy as the Convergence Criteria of Ant Colony Optimization and the Application at Gene Chip Data Analysis.

INTRODUCTION: When Ant Colony Optimization algorithm (ACO) is adept at identifying the shortest path, the temporary solution is uncertain during the iterative process. All temporary solutions form a solution set. METHOD: Where each solution is random. That is, the solution set has entropy. When the solution tends to be stable, the entropy also converges to a fixed value. Therefore, it was proposed in this paper that apply entropy as a convergence criterion of ACO. The advantage of the proposed criterion is that it approximates the optimal convergence time of the algorithm. RESULTS: In order to prove the superiority of the entropy convergence criterion, it was used to cluster gene chip data, which were sampled from patients of Alzheimer's Disease (AD). The clustering algorithm is compared with six typical clustering algorithms. The comparison shows that the ACO using entropy as a convergence criterion is of good quality. CONCLUSION: At the same time, applying the presented algorithm, we analyzed the clustering characteristics of genes related to energy metabolism and found that as AD occurs, the entropy of the energy metabolism system decreases; that is, the system disorder decreases significantly.

[Animal study in combining targeted-microbubbles with low-frequency ultrasound for the treatment of ischemic stroke].

OBJECTIVE: To study the treatment of ischemic stroke with combining targeted-microbubbles with low frequency ultrasound in animal model. METHODS: Cerebral thrombus animal model was established by the injection of autologous blood clots after cerebral angiogram through the carotid artery catheter in big white rabbit. With the confirm of thrombosis not being dissolved after angiography 6 h later, 49 big white rabbit were divided into four groups. Group A (n=13): direct injection of TMB through the vessel; group B (n=12): direct injection with nontargeted-microbubbles (NTMB) through the vessel; group C (n= 12): direct injection with tissue plasminogen activator (r-TPA) through the auricular vein; group D (n=12) injection with saline through the vessel as control. Group A, B, D was given with transcutaneous temporal LFUS (1 MHz at 2.0 W/cm2) for 30 minutes. At 0 h, 1 h and 2 h after the treatments, imaging observation of thrombolytic and blood flow recanalization were performed. The venous blood was collected before and at 2 h after the treatment in embolization for the detection of prothrombin time (PT), thrombin time (TT), fibrinogen (Fib) and the d-dimer. RESULTS: Group A rabbit had six of 13 (46.15%) success thrombolysis, group B 12 rabbit had 1 of (8.33%) success thrombolysis,group C had 4 of 12 (33.33%) success thrombolysis,group D had 1 of 12 (8.33%) success thrombolysis. The thrombolytic rates of group A, C were higher than those of group B and D (P<0.01). After the treatments, the differences of PT, APTT, TT, Fib and the d-dimer in A,B and D group were not statistically significant, and d-dimer in group C was higher than that in other groups (P<0.05). CONCLUSION: The treatment of combining targeted-microbubbles with low frequency ultrasound can rapidly release acute intracranial thrombotic occlusions, which has the same effect as r-TPA with less side effects.

Thrombolysis effect of a novel targeted microbubble with low-frequency ultrasound in vivo.

Clot-targeted microbubbles (TMB) were developed based on oligopeptide specific to the glycoprotein IIb/IIIa receptor on active platelets. In this study, we aimed to elucidate the thrombolysis effect of this TMB in both intraarterial and intravenous application and compare the clot lysis efficiency of the TMB and untargeted microbubbles(UTMB) in presence of external low frequency ultrasound (LFUS) (800 kHz, 2.4 w/cm(2), pulse-wave). An acute arterial occlusion model was induced in rabbits by blocking the common carotid artery with an autogenous clot. Animals were randomized to five groups to receive the following treatment: 1) intra-arterial TMB and LFUS (IA TMB/LFUS); 2) intravenous TMB and LFUS (IV TMB/LFUS); 3) intravenous untargeted-microbubbles and LFUS (IV UTMB/LFUS); 4) LFUS only; 5) intra-arterial normal saline (NS) control. Declotting score and a variation of thrombolysis-in-myocardial-infarction (TIMI) flow scale were applied to assess clot clearance and flow restore according to the angiogram. IA TMB/LFUS treatment produced highest declotting score (3.5 +/- 0.53) and success rate (100%). IV TMB/LFUS treatment produced a higher declotting score (1.95 +/- 1.12) than LFUS treatment (0.53 +/- 0.38) (P = 0.026). and higher TIMI (1.94 +/- 0.62 vs. 0.47 +/- 0.44, P = 0.020). When administrated intravenously, TMB/LFUS created a higher declotting score (1.95 +/- 1.12) than that of UTMB/LFUS (0.61 +/- 0.43) (P = 0.033). The superiority was observed in TIMI also (1.94 +/- 0.62 vs. 0.72 +/- 0.25, P = 0.041). The results demonstrate that either intra-arterial or intravenous TMB is effective in clearing clot in-vivo model. The TMB showed advantage over UTMB in systemic administration.

[Clinical selection of endovascular stenting and carotid endarterectomy in treatment of carotid artery stenosis].

OBJECTIVE: To explore reasonable clinical decision in treating carotid artery stenosis under different conditions. METHODS: The data of 133 carotid artery stenosis patients were retrospectively analyzed. Of the patients, 46 cases were treated with carotid angioplasty and stenting (CAS), 87 patients received carotid endarterectomy (CEA). The length of hospital stay and National Institutes of Health Stroke Scale (NIHSS) grade before and after treatment in both groups were observed; the forward flow were assessed by digital subtraction angiography (DSA) before and after treatment; the degree of carotid artery stenosis were determined by using ultrasound during 3 to 24 months after treatment in both groups; the cumulative incidence of major cardiovascular events was concentrated, including appearance of death, stroke or myocardial infarction during 30 days after CAS and CEA and death or homonymy stroke during 31 days to 2 years. RESULTS: Significant difference was found in hospital stay and when NIHSS exceed 20 after treatment between the two groups (P < 0.05); there was no significant difference in the forward flow before and after treatment in both groups; the carotid artery stenosis had been improved significantly after the operation in both groups; the cumulative incidence of major cardiovascular events in CEA group was significantly higher than in CAS group in 30 days after the operation (P < 0.05), but no statistical difference in 31 days to 2 years after the operation. CONCLUSIONS: CAS and CEA has equivalent effects in treating carotid artery stenosis, and should be selected according to the location of stenosis, etiological factors and the condition of opposite carotid artery.

[Comparision of different interventional therapies for primary liver cancer].

OBJECTIVE: To investigate the efficacy of different interventional therapies for primary hepatic cell cancer (HCC). METHODS: 1126 HCC patients before or after hepatectomy were treated by different kinds of interventional therapies: transcatheter arterial chemoembolization (TACE), TACE and radio-frequency ablation (RFA), Chinese traditional medicine and biotherapy after TACE or the transcatheter arterial infusion (TAI). The results of liver function, alpha-fetoprotein, imaging, color-ultrasonography and survival rate were reviewed. RESULTS: 874 patients were followed up for 2 to 63 months. The overall 1-, 3-, 5-year survival rate was 67.8% , 28.7% and 18.8%, respectively. The 1-, 3-, 5-year survival rate of patients who received TACE before hepatectomy was 74.7%, 41.4% and 36.9% ; after hepatectomy 78.9%, 40.4% and 37.5%, respectively. The response rate ( PR + NC) of TACE and RFA was 93.4%, and the 1-, 3-year survival rate was 74.5% and 36.8%, respectively, after TACE and RFA. The response rate (PR + NC) of TACE was 83.2% with 1-, 3-, 5-year survival rate of 69.3%, 21.7%, 8.4% after TACE, respectively. The response rate (PR + NC) of TAI was 27.5% with 1-, 2-year survival rate of 11. 6% and 0 after TAI. The Child grade of liver function, color-ultrasonography and alpha-fetoprotein of TACE + RFA group, TACE and TAI were compared. There was no significant difference between each above mentioned index among TACE, RFA or TACE groups. CONCLUSION: Compared with other modalities, transcatheter arterial chemoembolization (TACE) before or after hepatectomy is more effective than other interventional therapies for primary hepatocellular cancer, whereas, if combined with radiofrequency ablation (TAI), it is much more effective than TACE alone.

Comparison of therapeutic effectiveness of combined interventional therapy for 1126 cases of primary liver cancer.

AIM: To verify the effect of combined interventional therapy for hepatocellular carcinoma (HCC). METHODS: The clinical data of 1126 HCC patients who received combined interventional therapy for transcatheter arterial chemoembolization (TACE) before or after hepatectomy, TACE and radio-frequency ablation (RFA), Chinese medicine treatment and biotherapy after TACE or transcatheter arterial infusion (TAI), were reviewed according to the results of their liver function, alpha-fetoprotein, image data, color-ultrasonography finding and survival rate. RESULTS: A total of 874 patients were followed up for a period of 2 to 63 mo. The overall 1-, 3- and 5- year survival rates were 67.8%, 28.7% and 18.8% respectively. The 1- 3- and 5- year survival rates of patients who received TACE were 74.7%, 41.4%, 36.9% before hepatectomy and 78.9%, 40.4%, 37.5% after hepatectomy. The effective rate (PR + NC) after TACE and RFA was 93.4%, the 1- and 3- year survival rates were 74.5% and 36.8% after TACE and RFA. The effective rate of PR + NC after TACE was 83.2%. The 1-, 3- and 5- year survival rates were 69.3%, 21.7%, 8.4% after TACE. The effective rate of PR + NC after TAI was 27.5%, the 1- and 2- year survival rates were 11.6% and 0% after TAI. The liver function, color-ultrasonography finding and alpha-fetoprotein after TACE + RFA, TACE and TAI were compared. There was no significant difference in each index between TACE and RFA or TACE as well as in liver function between TACE and RFA or between TACE and TAI. CONCLUSION: The therapeutic effectiveness of TACE before or after hepatectomy is most significant, while the effect of TACE and RFA is better than that of TACE, and the effect of TAI is minimal.