Endothelial colony-forming cell-derived exosomal miR-21-5p regulates autophagic flux to promote vascular endothelial repair by inhibiting SIPL1A2 in atherosclerosis.

BACKGROUND: Percutaneous transluminal coronary angioplasty (PTCA) represents an efficient therapeutic method for atherosclerosis but conveys a risk of causing restenosis. Endothelial colony-forming cell-derived exosomes (ECFC-exosomes) are important mediators during vascular repair. This study aimed to investigate the therapeutic effects of ECFC-exosomes in a rat model of atherosclerosis and to explore the molecular mechanisms underlying the ECFC-exosome-mediated effects on ox-LDL-induced endothelial injury. METHODS: The effect of ECFC-exosome-mediated autophagy on ox-LDL-induced human microvascular endothelial cell (HMEC) injury was examined by cell counting kit-8 assay, scratch wound assay, tube formation assay, western blot and the Ad-mCherry-GFP-LC3B system. RNA-sequencing assays, bioinformatic analysis and dual-luciferase reporter assays were performed to confirm the interaction between the miR-21-5p abundance of ECFC-exosomes and SIPA1L2 in HMECs. The role and underlying mechanism of ECFC-exosomes in endothelial repair were explored using a high-fat diet combined with balloon injury to establish an atherosclerotic rat model of vascular injury. Evans blue staining, haematoxylin and eosin staining and western blotting were used to evaluate vascular injury. RESULTS: ECFC-exosomes were incorporated into HMECs and promoted HMEC proliferation, migration and tube formation by repairing autophagic flux and enhancing autophagic activity. Subsequently, we demonstrated that miR-21-5p, which is abundant in ECFC-exosomes, binds to the 3' untranslated region of SIPA1L2 to inhibit its expression, and knockout of miR-21-5p in ECFC-exosomes reversed ECFC-exosome-decreased SIPA1L2 expression in ox-LDL-induced HMEC injury. Knockdown of SIPA1L2 repaired autophagic flux and enhanced autophagic activity to promote cell proliferation in ox-LDL-treated HMECs. ECFC-exosome treatment attenuated vascular endothelial injury, regulated lipid balance and activated autophagy in an atherogenic rat model of vascular injury, whereas these effects were eliminated with ECFC-exosomes with knockdown of miR-21-5p. CONCLUSIONS: Our study demonstrated that ECFC-exosomes protect against atherosclerosis- or PTCA-induced vascular injury by rescuing autophagic flux and inhibiting SIAP1L2 expression through delivery of miR-21-5p. Video Abstract.

Thoracic Endovascular Repair for Aortic Arch Pathologies with Surgeon Modified Fenestrated Stent Grafts: A Multicentre Retrospective Study.

OBJECTIVE: To evaluate the outcome of thoracic endovascular repair (TEVAR) for aortic arch pathologies with surgeon modified fenestrated stent grafts. METHODS: A multicentre, retrospective study consisting of consecutive patients from seven centres treated with surgeon modified fenestrated stent grafts for aortic arch pathologies was conducted. A technique to align fenestrations and supra-aortic vessels was applied. Rates of technical success, mortality, complications, and re-interventions were evaluated. RESULTS: Between February 2016 and January 2020, 513 consecutive patients with aortic arch pathologies received TEVAR with surgeon modified fenestrated stent grafts. The technical success rate was 98.6% (n = 506). In total, 626 fenestrations were created to revascularise 684 branch arteries of the aortic arch. There were 13 deaths and 15 re-interventions within 30 days of the operation. The estimated clinical success rate at 30 days was 94.4% (95% confidence interval [CI] 92.4 - 96.4), the estimated survival at 30 days was 97.5% (95% CI 96.1 - 98.9), and the estimated freedom from re-intervention at 30 days was 97.1% (95% CI 95.7 - 98.5). The median follow up was 27 (interquartile range 13 - 31) months. During follow up, there were five aortic related deaths, three non-aortic related deaths, and four deaths of unknown cause. Eighteen patients underwent re-intervention. The estimated clinical success rate at 24 months was 88.2% (95% CI 85.5 - 91.0), the estimated survival at 24 months was 94.9% (95% CI 92.7 - 97.1), and the estimated freedom from re-intervention at 24 months was 93.1% (95% CI 91.0 - 95.3). In total, 18 cases of stroke were recorded, including 12 within 30 days and six during follow up; six cases of retrograde type A aortic dissection were recorded, including five within 30 days and one during the follow up. CONCLUSION: TEVAR with surgeon modified fenestrated stent grafts for the treatment of aortic arch pathologies provides acceptable outcomes. Further follow up is required to confirm the benefits of this approach.

Gene expression profiling analysis to investigate the role of remote ischemic postconditioning in ischemia-reperfusion injury in rats.

BACKGROUND: Blood flow restoration is a definitive therapy for salvaging the myocardium following ischemic injury. Nevertheless, the sudden restoration of blood flow to the ischemic myocardium can induce ischemia-reperfusion injury (IRI). RESULTS: Herein, we investigated the cardioprotective effect of remote ischemic postconditioning (RPostC) through our in vivo rat model of myocardial IRI. The study included three groups: the control group, the IRI group, and the IRI + RPostC group. Ischemia-reperfusion treatment led to an increase in the myocardial infarction area, which was inhibited by RPostC. In contrast to that in the control group, the myocardial apoptosis level was enhanced in the IRI group, whereas RPostC treatment decreased IRI-induced cellular apoptosis. Affymetrix Rat Gene 2.0 ST chip data identified a total of 265 upregulated genes and 267 downregulated genes between the IRI and IRI + RPostC groups. A group of differentially expressed noncoding RNAs (ncRNAs), such as MTA_TC0600002772.mm, MTA_TC1300002394.mm, U7 small nuclear RNA (Rnu7) and RGD7543256_1, were identified. Gene Ontology (GO) enrichment analysis indicated that the positive regulation of some molecular functions, such as GTPase activity, GTP binding, cyclic-nucleotide phosphodiesterase activity and cytokine activity, may contribute to the cardioprotective role of RPostC. Moreover, pathway enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes (KEGG) suggested the potential implication of the TNF signaling pathway and Toll-like receptor signaling pathway. Global signal transduction network analysis, co-expression network analysis and quantitative real-time polymerase chain reaction analysis further identified several core genes, including Pdgfra, Stat1, Lifr and Stfa3. CONCLUSION: Remote ischemic postconditioning treatment can decrease IRI-mediated myocardial apoptosis by regulating multiple processes and pathways, such as GTPase activity, cytokine activity, and the TNF and Toll-like receptor signaling pathways. The potential role of the above ncRNAs and core genes in IRI-induced cardiac damage merits further study as well.

Long Period and High Level of D-Dimer after Coronary Artery Bypass Grafting Surgery.

Hyper-coagulation after off-pump coronary artery bypass grafting (OPCAB) is one of the main reasons for graft thrombosis. D-dimer is closely linked to the activation of coagulation. Few studies have reported the variation range and long-term abnormal coagulation after OPCAB in the Chinese population. Our study aimed to determine the characteristics and value of D-dimer after OPCAB.In this prospective study, 265 patients who underwent OPCAB for the first time were recruited from 2011 to 2012. The D-dimer level of the patients was tested before surgery and on the 1st, 4th, and 14th day, and 1st, 2nd, and 3rd month after surgery. Clinical data in the perioperative period and during the one-year follow-up period were recorded.D-dimer level increased from day 4 after OPCAB ([1321.9 ± 36.4] µg/L), peaked at 1 month ([2839.7 ± 101.4] µg/L), and decreased to the baseline ([370.3 ± 260.2] µg/L) 3 months after surgery. No death occurred, but 25 (10%) patients suffered recurrent angina in the one-year follow-up. They had significantly higher D-dimer level at one month after OPCAB than those of patients who did not suffer from angina. Preoperative ejection fraction <50% and D-dimer level >2915 µg/L at one month after surgery were significantly associated the recurrent angina.After OPCAB, patients have a higher level of D-dimer. And this lasts for a long period (about 3 months). It may reflect a certain degree of hypercoagulable and hyperfibrinolytic state after OPCAB.

High Level of von Willebrand Factor in Non-ST Segment Elevation Myocardial Infarction Patients Predicted Cardiovascular Ischemic Events After Off-Pump Coronary Artery Bypass Surgery.

The aim of our study was to determine the characteristics and value of plasma von Willebrand factor antigen (vWF: Ag) levels after off-pump coronary artery bypass grafting (OPCAB) surgery in predicting the risk of cardiovascular ischemic events.A retrospective cohort analysis of 203 non-ST-segment elevation myocardial infarction patients was performed. Patients were divided into a poor recovery group and a stable condition group according to whether ischemic events occurred or not within 90 days postoperatively. The level of vWF: Ag was detected using a blood coagulation analyzer. SPSS17.0 statistical software was used for data analysis. The Friedman rank sum test and Mann-Whitney U test were used for intra-group and inter-group data analysis, respectively. The diagnostic performance of vWF: Ag was evaluated by receiver operating characteristic (ROC) curve analysis.Plasma vWF: Ag levels at postoperative days 14, 30, 60, and 90 in the poor recovery group were significantly higher than those at the corresponding time points in the stable group. The area under the ROC curve in diagnosing adverse events was 0.927 (95% CI: 0.867~0.987) with 96.6% sensitivity and 58.6% specificity when the cut-off value of vWF: Ag was 233% at postoperative day 30.The changing characteristics of plasma vWF: Ag sensitively reflect the degree of vascular endothelial injury of OP-CAB patients and might serve as a surrogate marker of the adverse event of non-ST segment elevation myocardial infarction.

Confined ischemia may improve remote myocardial outcome after rat cardiac arrest.

BACKGROUND: Confined ongoing ischemia after ischemia-reperfusion injury (IRI) may alter myocardial recovery. We evaluated in a rat cardiac transplantation model whether distal persistent myocardial ischemia (dMI) and remote preconditioning (RPreC) have a remote myocardial impact after IRI. MATERIAL AND METHODS: Syngeneic heterotopic cardiac transplantation was performed on 29 Fischer344 rats to induce IRI, including nine rats which underwent distal ligation of the left anterior coronary artery (LAD) to yield distal MI (IRI+ dMI). RPreC was applied by occluding the left renal artery 5 min prior to reperfusion in six rats with IRI (IRI+ RPreC) as well as in seven with distal MI (IRI+ dMI+ RPreC). Microdialysis, histology and qRT-PCR for inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) were performed after graft harvesting. RESULTS: In contrast to IRI + dMI + RPreC (39 ± 7 µmol), glutamate decreased in IRI + RPreC and IRI + dMI as compared with IRI (26 ± 3 and 31 ± 8 vs 91 ± 20, µmol respectively, p < 0.007). The relative number of vacuolated intramyocardial artery nuclei decreased in IRI + dMI as compared with IRI (0.02 ± 0.01, range 0-12 vs. 0.42 ± 0.31, range 0-3.25 PSU respectively, p < 0.04). iNOS expression decreased in IRI + RPreC as compared with IRI (p < 0.04), and eNOS expression decreased in IRI + dMI + RPreC as compared with IRI + dMI (p < 0.006) along with increased glycerol release. CONCLUSIONS: dMI after IRI has a potentially beneficial myocardial impact after cardiac arrest, which is hampered by RPreC.

Staging reinterventions for remodeling of residual aortic dissection: a single-center retrospective study.

Objective: Inadequate remodeling of residual aortic dissection (RAD) following repair of Stanford A or B aortic dissections has been identified as a significant predictor of patient mortality. This study evaluates the short- to mid-term outcomes of staged reinterventions for RAD at a single center with prospective follow-up. Methods: Data were retrospectively collected from patients with RAD who underwent staged reinterventions or received none-surgery treatment in the Cardiovascular Surgery Department of our hospital between July 2019 and December 2021. The cohort included 54 patients with residual distal aortic dissection post-primary surgery, comprising 28 who underwent open surgery and 26 who received thoracic endovascular aortic repair (TEVAR). Patients were divided into two groups: those who underwent staged stent interventions for distal dissection [staged reintervention (SR) group] and those who did not undergo surgery (non-surgery group). For the SR group, second or third staged stent interventions were performed. The study assessed distal remodeling of aortic dissection between the groups, focusing on endpoints such as mortality (both general and aortic-specific), occurrences of visceral branch occlusion, necessity for further interventions, and significant adverse events. Morphological changes were analyzed to determine the therapeutic impact. Results: The study encompassed 54 participants, with 33 in the SR group and 21 in the non-surgical control group. Baseline demographics and clinical characteristics were statistically comparable across both groups. During an average follow-up of 31.5 ± 7.0 months, aortic-related mortality was 0% in both groups; all-cause mortality was 3% (one case) and 5% (one case) in the SR and control groups, respectively, with no statistically significant difference noted. In the SR group, a single patient experienced complications, including renal artery thrombosis, leading to diminished blood flow. An increased true lumen (TL) area and a decreased false lumen area at various aortic planes were observed in the SR group compared to the control group. Conclusion: The staged reintervention strategy for treating RAD is safe and provides promising early results.

Application of the radial artery after angiography in patients undergoing total arterial coronary revascularization.

OBJECTIVE: There is growing evidence supporting the utilization of the radial artery as a secondary arterial graft in coronary artery bypass grafting (CABG) surgery. However, debates continue over the recovery period of the radial artery following angiography. This study aims to evaluate the clinical outcomes and experiences related to the use of the radial artery post-angiography in total arterial coronary revascularization. METHODS: A retrospective analysis was performed on data from patients who underwent total arterial CABG surgery at the University of Hong Kong Shenzhen Hospital from July 1, 2020, to September 30, 2022. Preoperative assessments included ultrasound evaluations of radial artery blood flow, diameter, intimal integrity, and the Allen test. Additionally, pathological examinations of the distal radial artery and coronary artery CT angiography were conducted, along with postoperative follow-up to assess the safety and efficacy of using the radial artery in patients undergoing total arterial CABG. RESULTS: A total of 117 patients, compromising 102 males and 15 females with an average age of 60.0 ± 10.0 years, underwent total arterial CABG. The internal mammary artery was used in situ in 108 cases, while in 4 cases, it was grafted to the ascending aorta due to length limitations. Bilateral radial arteries were utilized in 88 patients, and bilateral internal mammary arteries in 4 patients. Anastomoses of the proximal radial arteries to the proximal ascending aorta included 42 cases using distal T-anastomosis and 4 using sequential grafts. The interval between bypass surgery and coronary angiography ranged from 7 to 14 days. Pathological examination revealed intact intima and continuous elastic membranes with no significant inflammatory infiltration or hyperplastic lumen stenosis in the radial arteries. There were no hospital deaths, 3 cases of perioperative cerebral infarction, 1 secondary thoracotomy for hemorrhage control, 21 instances of intra-aortic balloon pump (IABP) assistance, and 2 cases of poor wound healing that improved following debridement. CT angiography performed 2 weeks post-surgery showed no internal mammary artery occlusions, but 4 radial artery occlusions were noted. CONCLUSION: Ultrasound may be used within 2 weeks post-angiography to assess the recovery of the radial artery in some patients. Radial arteries with intact intima may be considered in conjunction with the internal mammary artery for total arterial coronary CABG. However, long-term outcomes of these grafts require further validation through larger prospective studies.

Polymorphisms and high on-aspirin platelet reactivity after off-pump coronary artery bypass grafting.

OBJECTIVES: High on-aspirin residual platelet reactivity (RPR) after coronary artery bypass grafting (CABG) is a transient phenomenon with important implications for graft patency. This study was designed to determine the role of polymorphisms [TBXA2R (T924C), GPIIIa (Pl(A1/A2)), P2Y1 (A1622G), and GP1Bα (C1018T)] on RPR in Chinese patients undergoing off-pump CABG (OPCAB). METHODS: Of 420 patients recruited to this study, 210 patients underwent primary OPCAB and 210 controls with ischemic heart disease received optimal medical therapy. Arachidonic acid-induced platelet aggregation and urinary 11-dehydro thromboxane B2 were measured at baseline and following aspirin administration on days 1, 4, 10, and on 6th month. Four polymorphisms were identified [TBXA2R (T924C), P2Y1 (A1622G), Pl(A1/A2) and GP1Bα (C1018T)]. RESULTS: On the first post-operative day, 62 patients (29.5%) were with high RPR and 148 (70.5%) were with low RPR. Of the former, 33 (15.7%), 10 (4.6%), and 0 (0%) patients remained with high RPR on days 4, 10, and on 6 month, respectively. No individuals with high RPR was found in controls. Logistic regression identified TBXA2R-924TT (OR = 4.5; 95% CI, 1.8-11.1) and body mass index > 27 kg/m(2) (OR = 2.73; 95% CI, 1.1-7.0) as independent risk factors for high on-aspirin RPR. CONCLUSIONS: High on-aspirin RPR after OPCAB is associated with genetic polymorphism TBXA2R-924TT and obesity.

Efficacy of endovascular repair in the treatment of retrograde ascending aortic intramural haematoma.

BACKGROUND: The current treatment for retrograde ascending aortic intramural hematoma (RAIMH) remains challenging. This study aims to summarize the short-term results of endovascular repair in the treatment of retrograde ascending aortic intramural hematoma. METHODS: Between June 2019 and June 2021, 21 patients (16 males and 5 females) with a retrograde ascending aortic intramural hematoma, aged 53 ± 14years, received an endovascular repair in our hospital. All cases involved an ascending aortic or aortic arch intramural hematoma. 15 patients had an ulcer on the descending aorta combined with an intramural hematoma in the ascending aorta and 6 patients had typical dissection changes on the descending aorta combined with an intramural hematoma in the ascending aorta. All patients had a successful endovascular stent-graft repair, with 10 cases operated on in the acute phase (<14 days) and 11 cases in the chronic phase (14-35 days). RESULTS: A single-branched aortic stent graft system was implanted in 10 cases, a straight stent in 2 cases, and a fenestrated stent in 9 cases. All surgeries were technically successful. One of the patients developed a new rupture 2 weeks after surgery and was converted to a total arch replacement. No perioperative stroke, paraplegia, stent fracture or displacement, limb or abdominal organ ischemia occurred. The intramural hematomas started being absorbed on CT angiography images before discharge. There was no incidence of postoperative 30-day mortality, and the intramural hematomas in the ascending aorta and aortic arch were fully or partly absorbed. CONCLUSION: Endovascular repair of retrograde ascending aortic intramural hematoma was shown to be safe and effective, and correlated with favorable short-term results.

[Application of radial artery in total arterial coronary revascularization in elderly patients].

OBJECTIVE: To summarize the application experience and clinical effect of radial artery in total arterial coronary revascularization (TAR) in elderly patients. METHODS: Retrospectively analyzed the clinical data of patients who underwent TAR at the University of Hong Kong Shenzhen Hospital from July 1, 2020 to May 30, 2022. Patients were divided into ≥ 65-year-old group and < 65-year-old group according to age. The radial artery blood flow, diameter, intimal integrity and Allen test were evaluated by ultrasound before operation. The distal ends of radial artery were collected for pathological examination during operation. Coronary artery CT angiography (CTA) was examined postoperatively and follow up. The safety and reliability of ultrasonic assessment of radial artery and application of radial artery in elderly patients with TAR were summarized and analyzed. RESULTS: A total of 101 patients received TAR, including 35 cases aged ≥ 65 years old, 66 cases aged < 65 years old; 78 cases used bilateral radial arteries, and 23 cases used unilateral radial arteries. 4 cases of bilateral internal mammary arteries. All the proximal ends of the radial artery were anastomosed to the proximal end of the ascending aorta, 34 cases were performed of "Y" grafts, and 4 cases were sequential anastomoses. There was no in-hospital death and perioperative cardiovascular events. Perioperative cerebral infarction occurred in 3 patients. 1 patients was reoperated for bleeding. Intra-aortic balloon pump (IABP) assistance was used in 21 patients. Poor wound healing occurred in 2 cases and healed well after debridement. Follow-up of 2 to 20 months after discharge showed no internal mammary artery occlusion and 4 radial artery occlusions; no major adverse cardiovascular and cerebrovascular event (MACCE) occurred, and the survival rate was 100%. There was no significant difference in the above perioperative complications and follow-up endpoints between the two age groups. CONCLUSIONS: By adjusting the order of bypass anastomosis and optimizing the preoperative evaluation method, radial artery combined with internal mammary artery can obtain better outcome early in TAR, and can be safely and reliably applied to elderly patients.

MiR-144-5p/CCL12 Signaling Axis Modulates Ischemic Preconditioning-Mediated Cardio-protection by Reducing Cell Viability, Enhancing Cell Apoptosis, Fibrosis, and Pyroptosis.

Ischemic postconditioning (IPost) represents short periods of nonlethal ischemia-reperfusion performed at the onset of reperfusion. Studies have shown that IPost involves various biological processes such as cell proliferation, apoptosis, and pyroptosis and can activate complex signaling pathways. CCL12 is a critical mediator in the inflammatory process after tissue injury. In the present study, we examined the potential actions of CCL12-mediated signaling pathways in cardioprotection after IPost using a cardiomyocyte model. By applying the bioinformatics analysis, we found that CCL12 was upregulated in the rat heart tissues after I/R injury, and the expression level of CCL12 was restored in rats with IPost. The in vitro studies showed that CCL12 and CCR2 expression levels were upregulated in the hypoxia/reoxygenation (H/R)-induced H9C2 cells, which was attenuated in the H/R + hypoxia post-conditioning (PostC) group. The functional assays showed that H/R treatment reduced cell viability, increased cell apoptosis, and promoted fibrosis and pyroptosis of H9C2 cells, which was attenuated in the H/R + PostC group. Overexpression of CCL12 impaired the protective action of hypoxia post-conditioning in the H9C2 cells. Further mechanistic studies showed that miR-144-5p could directly target the 3' untranslated region of CCL12. Overexpression of miR-144-5p markedly repressed the expression levels of CCL12 and CCR2 in H9C2 cells, while miR-144-5p inhibition had the opposite effects. Furthermore, the inhibition of miR-144-5p reduced the cell viability, increased cell apoptosis, and enhanced fibrosis and pyroptosis of H9C2 cells after H/R or H/R + PostC treatment. In conclusion, CCL12 was downregulated in cardiomyocytes following ischemic postconditioning, and CCL12 overexpression impaired the cardioprotective actions of ischemic postconditioning by reducing cell viability, enhancing cell apoptosis, fibrosis, and pyroptosis. Further mechanistic evidence revealed that CCL12 was a direct target of miR-144-5p, and miR-144-5p/CCL12/CCR2 signaling may represent a critical pathway in mediating the cardioprotective effects of ischemic postconditioning.

Environmental and economic analysis of application of water hyacinth for eutrophic water treatment coupled with biogas production.

The proliferation of water hyacinth is currently controlled by removing it from a water body and disposing it by landfill in China. Using water hyacinth to remove nutrients from water bodies and to produce biogas is another technically feasible option for the control of water hyacinth, but its environmental and economic performances are not well understood. This study collected data from an experimental biogas plant to develop a lifecycle analysis and a cost benefit analysis for the control of water hyacinth proliferation in a eutrophic lake in China. Comparison was made between the alternative option of using water hyacinth for biogas production and the current practice of disposing it in landfills. The results reveal that the biogas option is economically feasible with a positive energy balance. The removal of water hyacinth to produce biogas can contribute to water quality improvement and GHG emission reduction whose values, however, depend on the processing scale of the biogas plant. Since both the current approach and the biogas option can remove nutrients from water bodies, the additional value of water quality improvement resulting from the biogas option is only possible when the processing scale of the biogas plant is greater than the amount of water hyacinth disposed by landfill. The emission of methane deserves attention when water hyacinth is disposed by landfill. The biogas option can respond to China's policies on water pollution control, renewable energy development, and energy saving and emission reduction.

Investigation into the role of Stmn2 in vascular smooth muscle phenotype transformation during vascular injury via RNA sequencing and experimental validation.

This study examined the effects of Stmn2 on phenotype transformation of vascular smooth muscle in vascular injury via RNA sequencing and experimental validation. Total RNA was extracted for RNA sequencing after 1, 3 and 5 days of injury to screen the differentially expressed genes (DEGs). Western blot was used to detect the protein expression of Stmn2 and its associated targets. The morphological changes of carotid arteries in rats were examined by hematoxylin and eosin (H&E) staining. The expression of vascular smooth muscle cell (VSMC) phenotype markers smooth muscle alpha-actin (α-SMA), vimentin and OPN were detected by immunohistochemistry. DEGs were related to the extracellular matrix and other cell components outside the plasma membrane. They were associated with protein binding, cytoskeleton protein binding, signal receptor binding and other molecular functions, actin cytoskeleton regulation and other Kyoto Encyclopedia of Genes and Genomes pathways. Stmn2 was identified as the hub gene of actin cytoskeleton pathway and vascular disease, and its expression followed the trend of decreasing initially and increasing afterwards during the progress of vascular injury. Western blot assay showed that the expression of Stmn2 and Tubulin decreased immediately after vascular injury; Stmn2 overexpression significantly up-regulated the expression of osteopontin and α-SMA and vimentin in VSMCs. The results of morphology analysis and immunostaining also showed that Stmn2 overexpression promoted the intima thickening and enhanced the proliferating cell nuclear antigen expression in the injured vascular tissues. In conclusion, our results implied that Stmn2 may play a potential role in vascular injury, which may be associated with VSMC phenotype transformation. Further studies are warranted to determine detailed molecular mechanisms of Stmn2 in vascular injury.

Osteoglycin knockdown promotes vascular smooth muscle cell proliferation and migration in aortic dissection via the VEGF/VEGFR2 axis.

Extracellular matrix (ECM) proteins serve a major role in the pathogenesis of aortic dissection (AD). The aim of the present study was to investigate the effect of osteoglycin (OGN), an ECM proteoglycan, on aortic dissection (AD), as well as the underlying mechanism. Thoracic aortic tissues from 20 patients with AD and healthy thoracic aortic tissue from 5 patients undergoing coronary artery bypass grafting were collected to detect OGN expression levels. Following OGN knockdown in rat aortic smooth muscle cells, cell proliferation was detected by performing Cell Counting Kit­8 and BrdU assays, cell migration was assessed by performing the wound healing assay, cell invasion was detected by performing the Transwell assay, and VEGFR/AKT signaling pathway­related protein expression levels were measured via western blotting. The results demonstrated that OGN expression was significantly downregulated in patients with AD compared with healthy controls. Compared with the si­negative control (NC) group, OGN knockdown promoted RASMC proliferation and migration. Compared with the si­NC group, OGN knockdown also significantly enhanced the phosphorylation of the downstream signaling molecules of VEGFR, including AKT and ERK1/2, in VEGF­stimulated RASMCs. Collectively, the present study indicated that OGN knockdown facilitated RASMC proliferation and migration by activating AKT and ERK1/2 signaling. Therefore, OGN may serve as a novel therapeutic target for AD.

The -251A>T polymorphism of interleukin-8 is associated with longer mechanical ventilation and hospital staying after coronary surgery.

BACKGROUND: Cardiac surgery is associated with inflammatory responses that are known to affect its outcome. The present study was designed to define whether post-operative release of interleukin (IL)-6, 8 and tumor necrosis factor-alpha (TNF-alpha) is related to the presence of a certain allele in functional polymorphism and its relationship to clinical outcome after off-pump coronary artery bypass (OPCAB). METHODS: One hundred and forty-five patients undergoing first time elective OPCAB were genotyped for IL-6(-174G>C), IL-8(-251A>T) and TNF-alpha(-308G>A) polymorphisms using polymerase chain reaction (PCR) and gene sequencing. Cytokine levels were measured in plasma samples taken before the operation and 4, 24 and 72h postoperatively by suspension array system. RESULTS: Levels of IL-6 and IL-8 increased significantly after OPCAB. Patients with IL-6-174GG and IL-8-251AA genotypes had higher post-operative circulating levels of IL-6 and IL-8, respectively. Logistic regression showed that IL-8-251AA genotype was an independent risk factor of ventilation time more than 1day (OR=11.80, 95% CI: 1.87-74.48) and hospital staying more than 14days (OR=38.00, 95% CI: 4.15-347.87) after surgery. CONCLUSIONS: OPCAB results in post-operative inflammatory responses. Genetic backgrounds alter the extent of inflammatory response and might relate to clinical outcome of OPCAB.

Perioperative brain natriuretic peptide in off-pump coronary artery bypass.

BACKGROUND: During the last decade brain natriuretic peptide (BNP) has been recognized as a useful marker for acute and chronic left ventricular dysfunction. The present study was designed to evaluate the clinical relevance of BNP before and after off-pump coronary artery bypass (OPCAB). METHODS: One hundred and twelve patients undergoing primary OPCAB were divided into two groups by preoperative BNP levels (group A, BNP < or = 100 pg/ml and group B, BNP > 100 pg/ml). Levels of BNP and MB isoenzyme of creatine kinase (CK-MB) were measured preoperatively, 6 hours and 1 day post-operatively. Echocardiographic and clinical data were collected. RESULTS: Patients in group A had smaller perioperative left ventricular end-diastolic dimensions (LVEDD) and greater left ventricular ejection fractions (LVEF) compared to group B (P < 0.05). Levels of BNP and CKMB increased postoperatively in both groups (P < 0.01). However, there was no relationship between postoperative BNP and CKMB at any time point. Logistic regression analyses showed that a preoperative BNP level > 100 pg/ml was an independent risk factor for ventilation > 24 hours (odds ratio, OR = 13.33; 95% CI: 1.42-125.03) and ICU stay > 72 hours (OR = 3.01; 95% CI: 1.09-8.33). CONCLUSION: The baseline BNP level correlated with preoperative ventricular function and longer durations of ventilation and hospital stay after OPCAB. BNP increased early after operation. However, postoperative BNP did not correlate with myocardial injury or clinical results after OPCAB.

[Association of polymorphisms of cytochrome P450 2C9 exon 4 and -65G>C with warfarin sensitivity].

OBJECTIVE: To investigate the association of the polymorphisms of cytochrome P450 2C9 (CYP2C9) exon 4 608T/G, 561A/C, 537A/C and 527A/C, and -65G/C with warfarin sensitivity. METHODS: A total of 102 patients under warfarin anticoagulant therapy were selected. During follow-up, warfarin dosage and associated Prothrombin Time-International Normalized Ratio (P-INR) values were recorded. Simultaneous monitoring of incidence of bleeding and thrombosis adverse effect was recommended. Genetic polymorphisms of the above mentioned loci were identified by polymerase chain reaction and DNA sequencing. RESULTS: The average age of the 102 patients was (62.1+/-10.5) years. The body mass index (BMI) was (24.7+/-3.8) kg/m2. Mean daily warfarin requirement was from 1.250 to 5.077 mg/day when therapeutic PT-INR (1.5-2.5) was maintained. DNA sequencing showed no polymorphisms of 608T/G, 561A/C, 537A/C, 527A/C in CYP2C9 exon 4. Warfarin daily dosage in CYP2C9 exon 4 -65C carriers was 3.106+/-0.619 mg/d, while it was (2.555+/-0.708) mg/d in individuals with wild-type -65G (P=0.020). Receiver operating characteristic (ROC) analysis showed that warfarin daily dosage of more than 2.5 mg/d can be used to predict the CYP2C9 exon 4 -65GC genotype (AUC: 0.770, P=0.005, 95%CI:0.626-0.915). Logistic regression indicated that BMI was an independent factor of bleeding during anti-coagulation therapy (OR=0.794, 95%CI: 0.651-0.970, P=0.024). CONCLUSION: The Chinese population are, generally, warfarin-sensitive. Exon 4 of the CYP2C9 gene is highly conserved in this population. The warfarin maintenance dosage in CYP2C9 exon 4 -65CG carriers was significantly higher than those with wild-type -65GG. The clinical significance needs further investigation with more large-scale, multi-center trials.

Determining the Influencing Factors of Biogas Technology Adoption Intention in Pakistan: The Moderating Role of Social Media.

Environmental degradation and rapid climate change have forced researchers and practitioners to find sustainable practices to save the world. Increasing energy demand is not only consuming scarce natural resources, but also damaging the climate and overall ecosystem. In this regard, biogas technology is beneficial in two ways-by meeting the energy demand and saving natural resources. Pakistan is an agricultural country and has a high potential for producing energy through biogas technology. Therefore, this study aims to find farmers' intentions of adopting biogas technology in Pakistan by employing the extended norm activation model. Furthermore, the moderating role of social media was explored. Purposive sampling was used to collect data from farmers and results were extracted by using Partial least square structural equation modelling software. The results suggest that awareness of consequences, ascription of responsibility, environmental concern and perceived consumer effectiveness positively and significantly influence personal norms of the farmers. Consequently, personal norms affect farmers' intentions of adopting biogas technology in Pakistan. The moderating role of social media was also confirmed by the results. This study considers the notable insights of biogas technology adoption in Pakistan. Finally, the limitations of the study and suggestions for future research are discussed.

Hybrid two-stage repair of Stanford A dissection with visceral or peripheral malperfusion.

BACKGROUND: The present study aimed to evaluate the effect of two-stage hybrid aortic repair at the distal aorta of Stanford A dissection with malperfusion. METHODS: This retrospective case series included 20 patients with Stanford A dissection administered two-stage thoracic endovascular aortic repair (TEVAR) about 1 month after central repair because of visceral or limb malperfusion. The patients were examined by computed tomography (CT) angiography at 3, 6, 12 and 24 months after operation. Recovery of malperfusion and true lumen index were evaluated during follow-up. RESULTS: Twenty patients underwent two-stage hybrid aortic repair, including 11 males and 9 females. The follow-up time was 24 ± 7 months. No intervention-related complications were observed, including stent graft-induced new re-entry tears, death, stroke and spinal cord injury. Malperfusion in all cases was corrected. The true lumen was not enlarged enough 1 month after the first surgery. Thrombosis of the false lumen was observed around the elephant trunk at the carina level and the celiac artery. Three months after second stage TEVAR, the false lumen thrombosis was resorbed; in addition, the trunk was fully expanded at the carina level, and the true lumen was enlarged at the celiac artery. CONCLUSIONS: Two-stage hybrid aortic repair for residual true lumen in the distal aorta 1 month after initial surgery is helpful for descending aorta remodeling and effective in treating malperfusion. This procedure may be a good option for patients suffering from Stanford A dissection with small true lumen in the distal aorta and malperfusion.