Baseline elevated Lp-PLA2 is associated with increased risk for re-stenosis after stent placement

BACKGROUND: Lipoprotein associated phospholipase A2 (Lp-PLA2) is a novel biomarker for cardiovascular risk prediction. Whether increased Lp-PLA2 level is associated with re-stenosis after stent-placement is unclear. METHODS: Totally 326 participants eligible for stent-placement were enrolled and divided into two groups according to baseline Lp-PLA2 levels (named normal and elevated groups). Baseline characteristics and clinical outcomes were compared between normal and elevated groups. The relationships between Lp-PLA2 and other risk factors with re-stenosis were evaluated. RESULTS: Only the between-group difference of Lp-PLA2 was significant (123.2 ± 33.6 ng/mL vs 336.8 ± 85.4 ng/mL, P < 0.001) while other demographic and clinical characteristics between these two groups were comparable. Approximately 55.1% and 58.5% of participants in normal and elevated groups presented with acute coronary syndrome, and the percentage of tri-vessels stenoses was significantly higher in elevated group (40.8% vs 32.1%, P = 0.016). Nearly 96.0% and 94.0% of participants in normal and elevated Lp-PLA2 groups were placed with drug-eluting stents, and the others were with bare-metal stents. After 1 year’s follow-up, the incidence of clinical end-points was comparable (13.3% vs 15.4%, P = 0.172). Nevertheless, the incidence of re-stenosis was marginally higher in elevated Lp-PLA2 group (8.5% versus 4.6%, P = 0.047). With multivariate analysis, after adjustment for other risk factors, Lp-PLA2 remained an independent predictor for re-stenosis with a hazard ratio of 1.140. No synergistic effect between Lp-PLA2 and other risk factors for re-stenosis was found. CONCLUSION: Increased Lp-PLA2 level is associated with an increased risk of re-stenosis. Lp-PLA2 assessment may be useful in predicting subjects who are at increased risk for re-stenosis

Analysis and Application of Eco-environmental Value of Saihanba Forest Farm Based on Fuzzy Analytic Hierarchy Process and K-Means Clustering

In this paper, we aim to establish an evaluation model for the impact of Saihanba on the ecological environment to quantitatively evaluate its impact due to its significant role on maintaining ecological balance and stability. We apply the fuzzy analytic hierarchy process method on building an evaluation model of Saihanba with a multilevel evaluation factor system. In addition, we promote the model with the help of the K-means clustering analysis method after optimizing to determine which geographical locations in China and Pakistan need to establish ecological reservation

Combination of multigrid with constraint data for inverse problem of nonlinear diffusion equation

This paper delves into a rapid and accurate numerical solution for the inverse problem of the nonlinear diffusion equation in the context of multiphase porous media flow. For the realization of this, the combination of the multigrid method with constraint data is utilized and investigated. Additionally, to address the ill-posedness of the inverse problem, the Tikhonov regularization is incorporated. Numerical results demonstrate the computational performance of this method. The proposed combination strategy displays remarkable capabilities in reducing noise, avoiding local minima, and accelerating convergence. Moreover, this combination method performs better than any one method used alone.Published versionThis research was funded by the Natural Science Foundation of Hebei Province of China (A2020501007), the Fundamental Research Funds for the Central Universities (N2123015), the Open Fund Project of Marine Ecological Restoration and Smart Ocean Engineering Research Center of Hebei Province (HBMESO2321), and the Technical Service Project of Eighth Geological Brigade of Hebei Bureau of Geology and Mineral Resources Exploration (KJ2022-021)

Atorvastatin treatment of rats with ischemia-reperfusion injury improves adipose-derived mesenchymal stem cell migration and survival via the SDF-1α/CXCR-4 axis.

BACKGROUND: Adipose-derived mesenchymal stem cells (ASCs) transplantation is a promising approach for myocardium repair. Promotion of ASCs migration and survival is the key for improving ASCs efficiency. SDF-1α is a critical factor responsible for ASCs migration and survival. Atorvastatin (Ator) is capable of up-regulating SDF-1α. Therefore, we're going to investigate whether ASCs migration and survival could be improved with atorvastatin. METHODS: In vitro study, cardiomyocytes were subjected to anoxia-reoxygenation injury and subsequently divided into different groups: group blank control, Ator, Ator plus L-NAME (A+L-NAME) and Ator plus AMD3100 (A+AMD3100).When migration analysis completed, cardiomyocytes were used for subsequent analyses. In vivo study, rats underwent ischemia-reperfusion injury were assigned into different groups corresponding to in vitro protocols. ASCs were transplanted on the seventh day of atorvastatin therapy. Seven days later, the rates of migration, differentiation and apoptosis were evaluated. RESULTS: Compared with other groups, ASCs migration in vitro was significantly improved in group Ator, which was dependent on SDF-1α/CXCR-4 coupling. Results of in vivo study were consistent with that of in vitro study, further supporting the notion that the efficacy of atorvastatin on ASCs migration improvement was related to SDF-1α/CXCR-4 axis. Higher vessel density in group Ator might be another mechanism responsible for migration improvement. Concomitantly, apoptosis was significantly reduced in group Ator, whereas no significant difference of differentiation was found. CONCLUSION: Migration and survival of ASCs could be improved by atorvastatin under ischemia-reperfusion injury, which were ascribed to SDF-1α/CXCR-4 axis

SDF-1α upregulation by atorvastatin in rats with acute myocardial infarction via nitric oxide production confers anti-inflammatory and anti-apoptotic effects

<p>Abstract</p> <p>Background</p> <p>The effects of atorvastatin on SDF-1α expression under acute myocardial infarction (AMI) are still unclear. Therefore, our present study is to investigate the roles and mechanisms of atorvastatin treatment on SDF-1α expression in rats with AMI.</p> <p>Methods</p> <p>Male Sprague–Dawley rats were underwent permanent coronary artery ligation and randomly assigned into four groups as follow: blank control (B), atorvastatin (A), atorvastatin plus L-NAME (A+L-NAME), and atorvastatin plus AMD3100 (A+AMD3100). Rats underwent similar procedure but without ligation were used as group sham operated (S). Atorvastatin (10mg/Kg/d body weight) was administrated by gavage to rats in three atorvastatin treated groups, and L-NAME (40mg/Kg/d body weight) or AMD3100 (5mg/Kg/d body weight) was given to group A+L-NAME or A+AMD3100, respectively.</p> <p>Results</p> <p>Comparing with group B, NO production, SDF-1α and CXCR4 expression were significantly up-regulated in three atorvastatin treated groups at the seventh day. However, the increments of SDF-1α and CXCR4 expression in group A+L-NAME were reduced when NO production was inhibited by L-NAME. Anti-inflammatory and anti-apoptotic effects of atorvastatin were offset either by decrease of SDF-1α and CXCR4 expression (by L-NAME) or blockage of SDF-1α coupling with CXCR4 (by AMD3100). Expression of STAT3, a cardioprotective factor mediating SDF-1α/CXCR4 axis induced cardiac protection, was up-regulated most significantly in group A. The effects of atorvastatin therapy on cardiac function were also abrogated either when SDF-1α and CXCR4 expression was diminished or the coupling of SDF-1α with CXCR4 was blocked.</p> <p>Conclusion</p> <p>SDF-1α upregulation by atorvastatin in rats with AMI was, at least partially, via the eNOS/NO dependent pathway, and SDF-1α upregulation and SDF-1α coupling with CXCR4 conferred anti-inflammatory and anti-apoptotic effects under AMI setting which we speculated that ultimately contributed to cardiac function improvement.</p

Study schematic and immuno-phenotype of ASCs.

<p>Panel (a) Schematic of the <i>in vivo</i> and <i>in vitro</i> experiment. Panel (b) CD29, CD31, CD44 and CD45 were detected by flow cytometry. Results showed that the fourth passage ASCs were largely positive for CD29 (99.80±0.10%) and CD44 (99.60±0.20%), and only minority of ASCs were positive for CD31 (0.30±0.10%) and CD45 (0.45±0.10%). The expression of CXCR4 on ASCs was 9.96±0.07%.</p

Comparison of ASCs apoptotic index <i>in vivo.</i>

<p><i> In vivo</i> apoptotic index was detected by TUNEL, and the results showed that compared with group blank control, atorvastatin therapy significantly reduced apoptotic index of ASCs, nevertheless, the efficacy was offset when either L-NAME or AMD3100 was added. (sham operated: 22.6±5.5, blank control: 52.1±9.4*, Ator: 31.3±6.7*#, A+L-NAME: 46.0±8.3*$, A+AMD3100: 49.7±7.8*$, per high power field). (Scale Bar: 50 µm).</p

Evaluation of ASCs migration and differentiation <i>in vivo</i>.

<p>Seven days after ASCs transplantation, immuno-staining analysis showed that in comparison of group blank control, the number of ASCs migrated in peri-infarcted areas was significantly increased in group Ator, however, the efficacy with atorvastatin therapy was abolished when SDF-1α up-regulation was diminished or SDF-1α/CXCR-4 coupling was blockage as shown in group A+L-NAME and A+AMD3100. (sham operated: 4.4±2.3, blank control: 13.3±2.2*, Ator: 22.6±2.9*#, A+L-NAME: 15.0±2.3*$, A+AMD3100: 14.5±2.5*$, per high power field). No significant difference was found in ASCs differentiation among each group (sham operated: 4.6±0.2%, blank control: 4.7±0.2%, Ator: 4.5±0.2%, A+L-NAME: 4.7±0.2%, A+AMD3100: 4.6±0.2%). (Scale Bar: 50 µm).</p

Comparisons of eNOS, p-eNOS, NO and SDF-1α levels in each group.

<p>Panel (a) Western-blot analysis showed that a significant increment of eNOS expression in group Ator, A+L-NAME and A+AMD3100 for <i>in vivo</i> study when compared with blank control. (sham operated: 0.28±0.07, blank control: 0.41±0.10*, Ator: 0.88±0.16*#, A+L-NAME: 0.93±0.15*#, A+AMD3100: 0.92±0.13*#). Similar changes were found in p-eNOS expression among each group (sham operated: 0.33±0.06, blank control: 0.46±0.11*, Ator: 0.93±0.14*#, A+L-NAME: 1.01±0.18*#, A+AMD3100: 0.95±0.16*#). Panel (b) Analyses of eNOS expression by Western-blot for <i>in vitro</i> study showed that as compared with group blank control, eNOS was significantly increased in group Ator, A+L-NAME and A+AMD3100. (sham operated: 0.42±0.08, blank control: 0.61±0.10*, Ator: 0.86±0.13*#, A+L-NAME: 0.89±0.11*#, A+AMD3100: 0.92±0.14*#). Similar changes were found in p-eNOS expression among each group (sham operated: 0.33±0.06, blank control: 0.50±0.09*, Ator: 0.76±0.11*#, A+L-NAME: 0.81±0.13*#, A+AMD3100: 0.78±0.10*#). Panel(c) When compared with group blank control, the NO productions <i>in vitro</i> and <i>in vivo</i> were identically and significantly increased in group Ator and A+AMD3100, whereas was abolished in group A+L-NAME. (<i>In vivo</i> study, sham operated: 6.03±1.10, blank control: 6.22±0.98, Ator: 10.31±0.86*#, A+L-NAME: 8.86±1.03*#, A+AMD3100: 11.10±0.92*#) and (in vitro study, sham operated: 3.62±0.42, blank control: 4.11±0.66, Ator: 7.03±0.71*#, A+L-NAME: 5.02±0.69*#, A+AMD3100: 7.11±0.70*#). Panel (d) As compared with group blank control, the SDF-1α expressions <i>in vitro</i> and <i>in vivo</i> was profoundly increased with atorvastatin therapy; however, the effects were reduced in group A+L-NAME. (<i>In vivo</i> study, sham operated: 5.53±0.73, blank control: 6.05±0.95, Ator: 10.88±1.33*#, A+L-NAME: 7.92±1.09*#, A+AMD3100: 9.86±1.21*#) and (in vitro study, sham operated: 3.84±0.47, blank control: 4.21±0.65, Ator: 8.12±0.77*#, A+L-NAME: 5.88±0.70*#, A+AMD3100: 7.76±0.73*#).</p