The dynamic changes in autophagy activity and its role in lung injury after deep hypothermic circulatory arrest.

Deep hypothermic circulatory arrest (DHCA) can cause acute lung injury (ALI), and its pathogenesis mimics ischaemia/reperfusion (I/R) injury. Autophagy is also involved in lung I/R injury. The present study aimed to elucidate whether DHCA induces natural autophagy activation and its role in DHCA-mediated lung injury. Here, rats were randomly assigned to the Sham or DHCA group. The sham group (n = 5) only received anaesthesia and air intubation. DHCA group rats underwent cardiopulmonary bypass (CPB) followed by the DHCA procedure. The rats were then sacrificed at 3, 6 and 24 h after the DHCA procedure (n = 5) to measure lung injury and autophagy activity. Chloroquine (CQ) was delivered to evaluate autophagic flux. DHCA caused lung injury, which was prominent 3-6 h after DHCA, as confirmed by histological examination and inflammatory cytokine quantification. Lung injury subsided at 24 h. Autophagy was suppressed 3 h but was exaggerated at 6 h. At both time points, autophagic flux appeared uninterrupted. To further assess the role of autophagy in DHCA-mediated lung injury, the autophagy inducer rapamycin and its inhibitor 3-methyladenine (3-MA) were applied, and lung injury was reassessed. When rapamycin was administered at an early time point, lung injury worsened, whereas administration of 3-MA at a late time point ameliorated lung injury, indicating that autophagy contributed to lung injury after DHCA. Our study presents a time course of lung injury following DHCA. Autophagy showed adaptive yet protective suppression 3 h after DHCA, as induction of autophagy caused worsening of lung tissue. In contrast, autophagy was exaggerated 6 h after DHCA, and autophagy inhibition attenuated DHCA-mediated lung injury.

False lumen patency status and outcomes after endovascular repair of uncomplicated chronic type B dissection.

BACKGROUND: Thoracic endovascular aortic repair (TEVAR) remains a controversial treatment for uncomplicated chronic type B aortic dissection (cTBAD). This study was performed to investigate the postoperative outcomes of TEVAR, such as survival and reintervention, and the risk factors for prognoses. METHODS: In total, 41 patients with uncomplicated cTBAD who underwent TEVAR from 2014 to 2021 were reviewed. The patients were divided into two groups: those with false lumen complete thrombosis (FLCT) and false lumen partial thrombosis (FLPT) based on computed tomography angiography (CTA) images. Kaplan-Meier analysis was performed to estimate survival and freedom from reintervention. Binary logistic analysis was performed to estimate risk factors for partial thrombosis. RESULTS: During a mean follow-up of 31 (1-78) months, five deaths and six reinterventions had occurred at 5 years. By 1 week, thoracic FLCT had occurred in 23 (56.1%) patients and thoracic FLPT had occurred in 18 (43.9%). The rate of freedom from reintervention was significantly lower in the FLCT than in the FLPT group (p = 0.04). The 5-year survival rate of the two groups was not statistically significant (p = 0.14). Risk factors for thoracic FLPT were the distance between the re-entry site and the graft (p = 0.02) and the proximal oversizing ratio (p = 0.04). CONCLUSIONS: TEVAR is an effective and safe treatment for uncomplicated cTBAD and has a low mortality rate. Thoracic FLCT is associated with less reintervention, but overall survival is not impacted by this difference. Patients treated with TEVAR without certain risk factors can have a good prognosis.

The effect of in situ laser fenestration for total endovascular arch repair in redo aortic dissection.

OBJECTIVE: Treatment of aortic arch pathologies in redo cases is technically challenging. In this study, we assessed early and mid-term outcomes of total endovascular arch repair combined with a new method of in situ laser fenestration. METHODS: Between January 2018 and March 2019, five patients with a history of cardiovascular surgery underwent in situ laser fenestration procedures using the "squid capture technique" for aortic arch pathologies with dissection. All patients were followed up regularly and imaging examinations were performed. The technical success, procedural complications, as well as the early and mid-term mortality and morbidity rates were evaluated. RESULTS: All patients survived the operation and fenestration was technically successful in all of the patients. There was no in-hospital mortality. No patients developed major complications, such as peri-operative strokes, transient ischemic attacks, or spinal cord ischemia. The 11-22 months follow-up (mean, 17 months) was completed by all patients. No endoleaks were discovered; false lumen thromboses and subsequent positive remodeling of the aorta were demonstrated and all in situ laser-fenestrated arteries were patent. CONCLUSIONS: In situ laser fenestration combined with "squid capture technique" was shown to may be an effective and safe option for reconstruction of aortic arch during thoracic endovascular aortic repair. In situ laser fenestration combined with "squid capture technology" was shown to be an effective treatment option for patients with prior history of cardiovascular surgery and who are at high risk for redo open operations.

Diabetic retinopathy predicts cardiovascular mortality in diabetes: a meta-analysis.

BACKGROUND: The prognostic significance of diabetic retinopathy (DR) for cardiovascular diseases (CVD) remained unclear. Therefore, we performed this meta-analysis to assess whether DR predicted CVD mortality in diabetic patients. METHODS: We searched PubMed, Embase, Web of Science and Cochrane Library for cohort studies reporting the association of DR and CVD mortality. Then we pooled the data for analysis. RESULTS: After screening the literature, 10 eligible studies with 11,239 diabetic subjects were finally included in quantitative synthesis. The pooled risk ratio (RR) of DR, mild DR, and severe DR for CVD mortality was 1.83 (95% confidence interval (CI): 1.42, 2.36; p < 0.001), 1.13 (95% CI 0.81, 1.59; p = 0.46), and 2.26 (1.31, 3.91; p = 0.003), respectively, compared to those without DR. In type 2 DM, the patients with DR had a significantly higher CVD mortality (RR: 1.69; 95% CI 1.27, 2.24; p < 0.001). Subgroup analysis also showed a significantly higher CVD mortality in DR according to various regions, study design, data source, and follow-up period (all RR > 1; all P values < 0.05). Data from 2 studies showed no significant correlation of DR and CVD mortality in diabetic patients receiving cardiovascular surgery (RR: 2.40; 95% CI 0.63, 9.18; P = 0.200). CONCLUSIONS: DR is a risk marker of cardiovascular death, and severe DR predicts a doubled mortality of CVD in diabetes. These findings indicate the importance of early identification and management of diabetic patients with DR to reduce the risk of death.

Retinal artery occlusion as the manifestation of left atrial myxoma: a case report.

BACKGROUND: Retinal artery occlusion caused by myxoma is relatively rare. There are several points that should be taken into consideration to avoid overlooking this disorder. CASE PRESENTATION: This case report describes a 43-year-old woman with sudden vision loss in her left eye for 20 days after single sudden syncope. Fundus examination of the left eye showed obscure boundary of optic disc with, reflective dispersion of the retina and poor light reflex of central fovea. A retinal artery occlusion was found in her left eye. Echocardiography revealed a tumor in the left atrium. Visual capacity improved a little during the follow-up. CONCLUSION: In any patients with retinal artery occlusion, detailed medical history and echocardiography should be carried out to exclude heart diseases.

Polymer-based delivering of shRNA to rabbit aortic smooth muscle cells suppressed the expression of IGF-1R in vitro and in vivo.

Restenosis is one of clinical limitations for vein graft in coronary bypass graft. It has been proved that signal pathway IGF-1 and its receptor (IGF-1R) activated by hemodynamic mechanical stretch are responsible for the vascular smooth muscle cells proliferation in vein graft neointima formation. Unfortunately, there is no routinely successful method to resolve this problem. Gene delivering to vein graft possesses great therapeutic potential to prevent neointima formation. Polymer is one kind of nanoparticles, which can activate the process of endocytosis of cells. In this study, we evaluated the transfection efficiency and therapeutic potential of polymer-based transfection of plasmids expressing GFP and shRNAs targeting IGF-1R (pGFPshIGF-1Rs) to smooth muscle cells and rabbit external jugular vein graft. Results showed that polymer-based transfection provided high efficiency of transgene expression in smooth muscle cells in vitro. In vitro, IGF-1R-specific shRNA transfected by polymer inhibited IGF-1R protein expression by 52 ± 3.6%, when compared with mock transfected cells. In vivo delivering efficiency of pGFPshIGF-1R plasmid into the rabbit external jugular vein graft was significantly high in the polymer-based transfection group, when compared with negative control group. In vivo, polymer-based transfection IGF-1R-specific shRNA efficiently inhibited the expression of IGF-1R protein by 77 ± 3.6%, 65.6 ± 4.9%, and 76.7 ± 4.3% at 24, 48, and 72 h, respectively, when compared with negative control group. Our findings indicated that polymer-based transfection may be a promising technique that allows the targeting of gene therapy for vein graft restenosis.

[Value of preoperative assessment on transcatheter aortic valve implantation procedure with high-pitch dual-source computed tomography angiography].

OBJECTIVE: To evaluate the value of preoperative assessment on transcatheter aortic valve implantation (TAVI) procedure with high-pitch dual-source computed tomography angiography (CTA). METHODS: Seventeen consecutive patients with severe symptomatic aortic stenosis underwent TAVI in our department from December 2012 to December 2013 were examined by 128-slice prospective ECG-triggered high-pitch spiral CTA and the clinical data were analyzed. Aortic annulus, sinus of Valsalva, sinotubular junction, ascending aorta and native leaflet to coronary ostium length were measured. Peripheral vascular access was evaluated. Then the patients were assessed on the suitability for TAVI procedure and prosthetic valve sizes. RESULTS: Mean diameter of the aortic annulus was (25.7 ± 2.0) mm, perimeter mean diameter was (26.4 ± 2.0) mm, area mean diameter was (25.4 ± 1.9) mm. Mean diameter of sinus of Valsalva was (34.0 ± 3.8) mm. Mean diameter of sinotubular junction was (30.5 ± 3.2) mm. Mean diameter of ascending aorta was (37.8 ± 2.8) mm. The length from native leaflet to left coronary ostium was (14.0 ± 2.0) mm, and the length from native leaflet to right coronary ostium was (15.9 ± 3.6) mm. Mean diameter of left iliac arteries was (7.5 ± 1.4) mm. Mean diameter of right iliac arteries was (7.4 ± 1.2) mm. Mean diameter of left femoral arteries was (7.4 ± 1.2) mm. Mean diameter of right femoral arteries was (7.3 ± 1.3) mm. One patient was considered ineligible for TAVI because of large aortic annulus diameter. Three patients died prior to TAVI. Two patients refused to undergo TAVI. Eleven patients underwent TAVI, 26# prosthetic valve was implanted in 1 patient, 29# prosthetic valve implanted in 6 patients, 31# prosthetic valve implanted in 4 patients. Prosthetic valve implantation was successful in 9 patients and only mild or trace perivalvular leakage was observed in these patients. Moderate perivalvular leakage were observed in 2 patients because of the location of implantation was too low, and perivalvular leakage was significantly reduced after re-implantation with same size prosthetic valve at a higher location. CONCLUSIONS: CTA can be used to evaluate the aortic root anatomy and vascular access, and help to choose the right size of prosthetic valve. CTA has an important practical value in preoperative screening of TAVI procedure.

The association between tea consumption and non-malignant digestive system diseases: A Mendelian randomized study.

BACKGROUND: Tea consumption might be closely related to non-malignant digestive diseases. Nevertheless, this correlation remains inadequately comprehended. Therefore, our objective was to elucidate the essence of these connections. METHODS: This study employed a Mendelian randomization approach to investigate the impact of tea consumption on specific digestive disorders. Genetic data associated with tea consumption were obtained from the UK Biobank (UKB), encompassing 447,485 participants. We chose a gene-wide association study with no sample overlap and UKB as our data source for all outcomes. The primary analytical method utilized was inverse variance weighting, and multiple analytical models were employed to enhance the analysis's reliability and ensure robust results. RESULT: Our investigation revealed that tea consumption was linked to an elevated susceptibility to gastroesophageal reflux disease (GERD). However, there was a lack of substantial evidence suggesting an association between tea intake and Crohn's disease (CD), ulcerative colitis (UC), or non-alcoholic fatty liver disease (NAFLD). CONCLUSIONS: Our study suggests that the excessive consumption of tea may heighten the likelihood of GERD. These results hold potential significance in guiding dietary pattern modifications for individuals with GERD. Furthermore, there may be value in implementing GERD monitoring and preventive measures in populations with elevated tea consumption.

Inhibition of Taurine-upregulated Gene 1 Upregulates MiR-34a-5p to Protect against Myocardial Ischemia/Reperfusion via Autophagy Regulation.

BACKGROUND: Taurine upregulated gene 1 (TUG1) has been identified on long noncoding RNA (lncRNA); however, its function in myocardial cells following ischemia/ reperfusion (I/R) injury has not been explored. This study aimed to investigate the role of LncTUG1 in I/R injury by focusing on its relationship with autophagy induction by regulating miR-34a-5p expression. METHODS: We established a myocardial I/R model and H9C2 hypoxia-ischemic and reoxygenation (HI/R) conditions to induce I/R injury. TTC, Western blot, CCK-8 assay, quantitative reverse transcription PCR, flow cytometry, and confocal microscopy were used to assess the size of myocardial infarct, level of some apoptotic-related and autophagy-associated proteins, cell viability, the level of LncRNA TUG1, apoptosis, and autophagy, respectively. RESULTS: The results revealed that a TUG1 knockdown protected against I/R-induced myocardial injury by decreasing the impairment in cardiac function. LncRNA TUG1 expression was increased in a myocardial I/R model and HI/R in H9C2 cells. Moreover, inhibition of LncTUG1 enhanced H9C2 cell viability and protected the cells from HI/R-induced apoptosis. Silencing LncRNA TUG1 promoted HI/R-induced autophagy. Furthermore, TUG1 siRNA upregulated the level of miR-34a-5p compared to the HI/R group. The protective effect of LncRNA TUG1 inhibition on H9C2 cells following HI/R was eliminated by blocking autophagy with an miR-34a-5p inhibitor. CONCLUSION: These findings indicated that inhibiting TUG1 may reduce the extent of myocardial I/R injury by regulating miR-34a-5p. Taken together, these results suggest that LncRNA TUG1 may represent a novel therapeutic target for myocardial I/R injury.

Shared genetic etiology of vessel diseases: A genome-wide multi-traits association analysis.

BACKGROUND: The comorbidity among vascular diseases has been widely reported, however, the contribution of shared genetic components remains ambiguous. METHODS: Based on genome-wide association study summary statistics, we employed statistical genetics methodologies to explore the shared genetic basis of eight vascular diseases: coronary artery disease, abdominal aortic aneurysm, ischemic stroke, peripheral artery disease, thoracic aortic aneurysm, phlebitis, varicose veins, and venous thromboembolism. We assessed global and local genetic correlations among these disorders by linkage disequilibrium score regression, high-definition likelihood, and local analysis of variant association. Cross-trait analyses conducted with CPASSOC identified pleiotropic variants and loci. Further, biological pathways at the multi-omics level were explored using multimarker analysis of genomic annotation, transcriptome-wide and proteome-wide association studies. Causal associations among the vascular diseases were evaluated by mendelian randomization and latent causal variable to assess vertical pleiotropic effects. RESULTS: We found significant global genetic associations in 18 pairs of vascular diseases. Additionally, we discovered 317 unique genomic regions where at least one pair of traits demonstrated significant correlation. Multi-trait association analysis identified 19,361 significant potential pleiotropic variants in 274 independent pleiotropic loci. Multi-trait colocalization analysis revealed 56 colocalized loci in specific disease sets. Gene-based analysis identified 700 potential pleiotropic genes, which were subsequently validated at both transcriptome and protein levels. Gene-set enrichment analysis supports the role of biological pathways such as vessel wall structure, coagulation and lipid transport in vascular disease. Additionally, 7 pairs of vascular diseases have a causal relationship. CONCLUSIONS: Our study indicates a shared genetic basis and the presence of common risk genes among vascular diseases. These findings offer novel insights into potential mechanisms underlying the association between vascular diseases, as well as provide guidance for interventions and treatments of multi-vascular conditions.

Thrombotic Thrombocytopenia Purpura (TTP) following emergent aortic valve replacement after a complicated TAVR procedure: a case report and review of the literature.

BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is a rare hematological disorder. The occurrence of TTP subsequent to an emergent aortic valve replacement after a TAVR procedure is exceedingly uncommon with only a few reported cases worldwide. CASE PRESENTATION: We report the case of a 70-year-old female patient diagnosed with aortic insufficiency. Following a transcatheter aortic valve replacement, she underwent emergency aortic valve replacement under cardiopulmonary bypass on the subsequent day due to heart valve displacement. The postoperative diagnosis revealed TTP and symptomatic treatment involving plasma exchange was administered. After demonstrating steady improvement, the patient was eventually discharged. CONCLUSION: Aortic valve replacement after TAVR is a high-risk procedure and increases susceptibility for developing secondary TTP. The diagnosis and treatment of secondary TPP is considerably challenging, and early diagnosis with symptomatic treatment including plasma exchange can increase patient survival.

The Role of Inflammatory Biomarkers in Mediating the Effect of Inflammatory Bowel Disease on nonmalignant Digestive System Diseases: A Multivariable Mendelian Randomized Study.

Background: While observation studies have shown a positive correlation between inflammatory bowel disease (IBD) and the risk of nonmalignant digestive system diseases, a definitive causal relationship has not yet been clearly established. Methods: Mendelian randomization (MR) was employed to investigate the potential causal association between genetic susceptibility to IBD and nonmalignant gastrointestinal diseases. Genetic variants were extracted as instrumental variables (IVs) from a genome-wide association study (GWAS) meta-analysis, which included 12,194 cases of Crohn's disease (CD) and 28,072 control cases of European ancestry. The GWAS for ulcerative colitis (UC) included 12,366 UC and 33,609 control cases of European ancestry. All IVs reached genome-wide significance (GWAS p value <5 × 10-8). Summary-level data for acute pancreatitis (AP), irritable bowel syndrome (IBS), gastroesophageal reflux disease, cholelithiasis, and CeD (celiac disease) were obtained from the GWAS meta-analysis and the FinnGen dataset. Summary-level data on relevant inflammatory factors were provided by the International Genetic Consortium. Univariate MR analysis was conducted using inverse variance weighting as the primary method for estimating causal effects. Multivariate MR analyses were also performed to detect possible mediators. Results: Genetic susceptibility to UC was associated with an increased risk of AP (OR = 1.08; 95% CI = 1.03-1.13; p=0.002) and IBS odds ratio (OR] = 1.07; 95% confidence interval (CI] = 1.03-1.11; (p < 0.001). In terms of potential mediators, interleukin 6 (IL-6) had a driving effect on the association between UC and AP. There was no apparent evidence of increased risk with CD. Meanwhile, genetic susceptibility to CD increases the risk of CeD (OR = 1.14; 95% CI = 1.03-1.25; p=0.01). Conclusions: The evidence suggests that UC is associated with an elevated risk of AP and IBS, and IL-6 may be responsible in AP. CD is associated with an increased risk of developing CeD. Implementing a proactive monitoring program for assessing the risk of gastrointestinal diseases in UC patients, particularly those with elevated IL-6 levels, may be of interest. In addition, the presence of AP and IBS may indicate the presence of UC. Preventing CeD is an essential consideration in the therapeutic management of patients with CD.

VENOARTERIAL EXTRACORPOREAL MEMBRANE OXYGENATION REDUCES MYOCARDIAL AND MITOCHONDRIAL DAMAGE IN ACUTE MYOCARDIAL INFARCTION.

ABSTRACT: Background: Myocardial infarction (MI) is a common cardiovascular disease with a high fatality rate once accompanied by cardiogenic shock. The efficacy of extracorporeal membrane oxygenation (ECMO) in treating MI is controversial. Methods: MI was induced by ligating the left anterior descending artery (LAD) in adult male rats. Groups were defined as follows: MI group, reperfusion for 90 min after 30 min of LAD occlusion; MI + ECMO group, reperfusion and ECMO were performed for 90 min immediately after 30 min of LAD occlusion; prolonged MI + ECMO group, ECMO was used immediately after 30 min of occlusion with persistent occlusion of the LAD for an additional 30 min, followed by 90 min of reperfusion. The myocardial infarct size and mitochondrial morphology and function data were collected and compared of each group. Results: The ECMO groups had a smaller myocardial infarct size and larger percentage ejection fraction. Compared with the prolonged MI + ECMO group, the immediate reperfusion group had a lower percentage of infarct size (63.28% vs. 17.97% vs. 31.22%, MI vs. MI + ECMO vs. prolonged MI + ECMO). Mitochondria isolated from the ischemic zone showed an intact mitochondrial structure, including fewer voids and broken cristae, and preserved activity of mitochondrial complex II and complex IV in ECMO groups. Conclusions: ECMO support in MI can reduce myocardial injury despite delayed coronary reperfusion.

MicroRNA-150 aggravates H2O2-induced cardiac myocyte injury by down-regulating c-myb gene.

MicroRNAs (miRNAs) are one class of non-coding RNAs that play an important role in post-transcriptional regulation via the degradation or translational inhibition of their target genes. MicroRNA-150 (miR-150) plays a vital role in regulating the development of B and T lymphocytes. Although the dysregulation of miR-150 was confirmed in human myocardial infarction, little is known regarding the biological functions of miR-150 in response to reactive oxygen species (ROS)-mediated gene regulation in cardiac myocytes. Using quantitative real-time reverse transcription-polymerase chain reaction, we demonstrated that the level of miR-150 was up-regulated in cardiac myocytes after treatment with hydrogen peroxide (H2O2). To identify the potential roles of miR-150 in H2O2-mediated gene regulation, we modulated expression of miR-150 using miR-150 inhibitor and miR-150 mimics. Results showed that silencing expression of miR-150 decreased H2O2-induced cardiac cell death and apoptosis. In lymphocytes, c-myb was a direct target of miR-150. In cardiac myocytes, we found that c-myb was also involved in miR-150-mediated H2O2-induced cardiac cell death. These results suggested that miR-150 participates in H2O2-mediated gene regulation and functional modulation in cardiac myocytes. MiR-150 may play an essential role in heart diseases related to ROS, such as cardiac hypertrophy, heart failure, myocardial infarction, and myocardial ischemia/reperfusion injury.

Can Posterior Pericardial Incision Truly Improve Postoperative Complications After Cardiac Surgery? A Systematic Review and Meta-Analysis.

INTRODUCTION: Postoperative atrial fibrillation (POAF) and pericardial effusion are important factors affecting prognosis after cardiac surgery. Recently, it has been reported that posterior pericardiotomy (PP) can effectively prevent the occurrence of POAF and pericardial effusion. To validate these conclusions and guide clinical practice, we conducted a systematic review with meta-analysis. METHODS: We searched multiple databases for manuscripts published before July 2022 on the use of PP to prevent POAF and pericardial effusion and included only randomized controlled trials. The main outcome was atrial fibrillation after coronary artery bypass grafting, and secondary outcomes were included. RESULTS: This meta-analysis included 14 randomized controlled trials with a total of 2275 patients. Meta-analysis showed that the incidence of POAF after cardiac surgery in the PP group was significantly lower than that in the control group (risk ratio=0.48; 95% confidence interval=0.33~0.69; P<0.00001). PP effectively reduced postoperative pericardial effusion (risk ratio=0.34, 95% confidence interval=0.21-0.55; P<0.00001). CONCLUSION: PP has shown good results in preventing POAF, pericardial effusion, and other complications, which indicates that PP is a safe and effective surgical method, but attention still needs to be paid to the potential risk of coagulation dysfunction caused by PP.

Deficiency of GDF-11 Accelerates TAC-Induced Heart Failure by Impairing Cardiac Angiogenesis.

The role of growth differentiation factor (GDF)-11 in cardiac diseases has not been fully determined. Our study revealed that GDF-11 is not essential for myocardial development and physiological growth, whereas its absence exacerbates heart failure under pressure overload condition via impairing the responsive angiogenesis. GDF-11 induced VEGF expression in CMs by activating the Akt/mTOR pathway. The effect of endogenous GDF-11 on the heart belongs to local self-regulation of myocardial tissue, rather than a way of systemic regulation.

Tissue distribution and cancer growth inhibition of magnetic lipoplex-delivered type 1 insulin-like growth factor receptor shRNA in nude mice.

The targeted delivery of therapeutic genes into specific tissues, as well as the determination of the biological fate and potential toxicity of nanoparticles, remains a highly relevant challenge for gene-based therapies. Type 1 insulin-like growth factor receptor (IGF-1R), an important oncogene, is frequently over-expressed in lung cancer and mediates cancer cell proliferation as well as tumor growth. In our previous studies, we have successfully applied gene delivery mediated by commercially available nanoparticles (CombiMAG) under a magnetic field, which suppresses IGF-1R expression in a non-small cell lung cancer cell line (A549) in vitro. In the present study, we aimed to investigate the biological distribution and target tumor suppression of magnetofection, as well as its potential toxicity via CombiMAG-carrying plasmids expressing green fluorescent protein (GFP) and short hairpin RNAs (shRNAs) targeting IGF-1R (pGFPshIGF-1Rs) in tumor-bearing mice. The peak expression in various organs appeared 48 h after transfection. Transgene expression via magnetofection was 3-fold improvement than via lipofection. On the 30th day after injection, the tumor size and weight of the CombiMAG-treated group (789.32 ± 39.43 mm(3), 105.5 ± 6.1 mg) were significantly decreased compared with those of the lipofection group (893.83 ± 31.23 mm(3), 164.5 ± 9.1 mg; P< 0.05), and the suppression rate was ∼36%. After a 30-day observation, the injection of CombiMAG did not cause any apparent toxicity. Therefore, IGF-1R shRNA nanoparticles can be valuable and safe delivery agents for RNA interference therapy to tumors in vivo.

[Magnetic liposome mediated shRNA specifically suppresses the growth of non-small cell lung cancer in vitro and in vivo].

OBJECTIVE: To evaluate the inhibition of shRNA mediated by magnetic liposome in the growth of non-small cell lung cancer (NSCLC) under the interference of magnetic field in vitro and in vivo and explore the effects of magnetic field on the efficiency of magnetofection. METHODS: The plasmid of pGFPshIGF-1R was constructed for expressing GFP and shRNA against IGF-1R. CombiMAG as superparamagnetic iron oxide nanoparticles (SPIONs) and Lipofectamine2000 as cationic liposome comprised the magnetic liposome. pGFPshIGF-1R was transferred into A549 cells by magnetofection under a series of interaction durations and intensity of external magnetic fields. pGFPshIGF-1R was delivered into A549 cells in vitro and injected intravenously into the tumor-bearing mice every 48 h for four doses in vivo by way of lipofection or magnetofection. The magnetofection efficiency was analyzed by cytometry and the potency of IGF-1R knockdown by Western blot. At Week 3 after the 4th injection, the mice were sacrificed and the tumors removed and weighed. The tumor inhibition rate was calculated. RESULTS: The interaction durations and intensity of magnetic field could influence the magnetofection efficiency. In vitro, IGF-1R specific-shRNA transfected by lipofection inhibited IGF-1R protein by 56.1% ± 6.0% and by liposomal magnetofection by 85.1% ± 3.0%. In vivo, pGFPshIGF-1R delivered by both lipofection and magnetofection significantly inhibited the tumor growth by 41.3% (P < 0.01) and 65.2% (P < 0.01). CONCLUSIONS: Based on magnetic liposome as gene vectors, magnetofection may become a promising targeted therapy for lung cancer. And the transfection efficiency is influenced by magnetic field.

[One-stop hybrid cardiac surgery for adults with complex heart disease].

OBJECTIVE: To evaluate the efficacy and security of one-stop hybrid cardiac surgery for the treatment of adult patients with complex heart disease. METHODS: From November 2011 to March 2012, a total of 5 patients [4 male, mean age: (58.8 ± 14.7) years] underwent one-stop hybrid approach in the hybrid operating room. Two patients suffered from multi-coronary lesions, 2 patients were diagnosed with both valvular heart disease and coronary disease, and another 1 patient had valve disease and congenital heart disease (patent ductus arteriosus). Minimally invasive cardiac surgery (coronary artery bypass grafting for the left anterior descending or valvular surgery) and percutaneous intervention were performed in an enhanced operative unit. The efficacy and security of one-stop hybrid cardiac surgery were evaluated after the procedure. RESULTS: The one-stop hybrid procedure was successful in all patients. Left internal mammary artery grafts were unobstructed. A total of 6 non-left anterior descending coronary lesions were treated by percutaneous coronary intervention and 6 drug-eluting stents were implanted. There was no death, perioperative myocardial infarction, heart failure, prosthetic valve dysfunction, respiratory failure, stroke or repeat surgery during the procedure period. All patients remained free from angina, prosthetic valve dysfunction and patent ductus arteriosus recanalisation during the 3.2 months (rang 1 to 5 months) follow-up period. CONCLUSION: One-stop hybrid cardiac surgery provides a reasonable, feasible and safe alternative for treating adult patients with complex heart disease.

Transcoronary sinus repair of a severely dilated and tortuous right coronary artery fistulized to coronary sinus complicated with tricuspid valve insufficiency.

BACKGROUND: Right coronary artery (RCA) fistulized to the coronary sinus is rare condition in adult cardiac anomalies, and the management and operative indication are controversial. CASE PRESENTATION: We describe the case of a 45-year female patient who presented with exertional dyspnea, accompanied by intermitted lower limbs and facial edema. She was diagnosed with severe tricuspid regurgitation second to a severely dilated RCA fistulized to the coronary sinus. After multidisciplinary discussion, she underwent surgery through routine medium sternotomy, the right atrium was opened under cardiopulmonary bypass. The coronary arteriovenous fistula from the distal portion of RC to a severely enlarged coronary sinus was found. Trans-coronary sinus closure of the fistula was performed with continuous stitching and a tricuspid ring annuloplasty was done. The patient recovered uneventful post operation. CONCLUSION: According to current literatures, surgical treatment was adopted for this case, instead of endovascular intervention. The optimal approach for these cases should consider the heart's anatomical characteristics. But we need to be aware of the occurrence of myocardial infarction and tricuspid regurgitation in the early and late stage after operation.