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.

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.

In situ laser fenestration for revascularization of aortic arch during treatment for iatrogenic type A aortic dissection.

BACKGROUND: Iatrogenic aortic dissection is a rare and fatal complication. Its treatment was challenging and controversial especially in patients with previous cardiac procedure. This study aimed to present the case of a patient with aortic dissection after previous open cardiac surgery who was successfully treated by in situ laser fenestration for revascularization of aortic arch. CASE PRESENTATION: A 65-year-old man suffered severe aortic and mitral valve regurgitation was treated by open cardiac aortic valve replacement (biological valve, Edwards) and mitral valve repair. During the sixth-month follow-up, computed tomography angiography (CTA) scan revealed an aortic dissection that extended from the ascending aorta to both femoral arteries. After stabilized by medical treatment, the patient was treated by endovascular stent-graft implantation and in situ laser (holmium laser, energy: 0 5 J, frequency: 5 Hz.) fenestration for revascularization of aortic arch in our one-stop hybrid operating room. The patient recovered without any clinical complication and was discharged 5 days after the procedure. CONCLUSIONS: Our work suggested that in situ laser fenestration for revascularization of aortic arch is a feasible, effective, and safe treatment in patients with iatrogenic aortic dissection.

Xuebijing in the treatment of patients with sepsis.

BACKGROUND: There are more than 18 million patients diagnosed with sepsis every year. In China, Xuebijing (XBJ) injection is a traditional medicine that is widely used in the treatment of sepsis. However, the efficacy of XBJ in treatment of randomized controlled trials (RCTs) remains unclear. This meta-analysis was to evaluate the clinical efficacy of XBJ based on randomized case-control studies. METHODS: PubMed, Cochrane, Embase, Wanfang, CNKI, and WeiPu (VIP) databases were searched to identify all the relative randomized case-control. The latest research was done in June, 2016. Relative risks (RR), weighted mean difference (WMD) along with 95% confidence interval (95%CI) were used to analyze the main outcomes. Statistical analysis was performed using STATA 10.0 (TX, USA). The qualities of the involved articles were accessed by the Jadad scale. RESULTS: Forty-nine randomized case-control studies met the inclusion and exclusion criteria, with 1861 patients in the control group and 2023 patients in the XBJ group. Compared with the conventional therapy, XBJ injection could significantly reduce the APACHE-IIscore (WMD: -3.70, 95%CI: -4.31-[-3.09]), PCT (WMD: -1.26µg/L, 95%CI: -1.63µg/L-[-0.88µg/L]), WBC (WMD: -1.48×109/L, 95%CI: -2.03×109/L-[-0.94×109/L]), CRP (WMD: -24.38mg/L, 95%CI:-30.49mg/L-[-18.26mg/L]), NEU (WMD: -4.68, 95%CI: -8.32-[-1.04]), T0(WMD: -0.50, 95%CI: -0.92-[-0.07]). The 28-day mortality of the XBJ group was significantly lower than the control group (RR: 0.51; 95%CI: 0.44-0.59). CONCLUSION: XBJ injection has a significant clinical efficacy in the therapy of patients with sepsis. However, there is a need for more randomized, lager-sample size, high-quality, and multicenter studies to confirm the extract efficacy of XBJ injection.

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.

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.

Tumor-targeting magnetic lipoplex delivery of short hairpin RNA suppresses IGF-1R overexpression of lung adenocarcinoma A549 cells in vitro and in vivo.

Liposomal magnetofection potentiates gene transfection by applying a magnetic field to concentrate magnetic lipoplexes onto target cells. Magnetic lipoplexes are self-assembling ternary complexes of cationic lipids with plasmid DNA associated with superparamagnetic iron oxide nanoparticles (SPIONs). Type1 insulin-like growth factor receptor (IGF-1R), an important oncogene, is frequently overexpressed in lung cancer and mediates cancer cell proliferation and tumor growth. In this study, we evaluated the transfection efficiency (percentage of transfected cells) and therapeutic potential (potency of IGF-1R knockdown) of liposomal magnetofection of plasmids expressing GFP and shRNAs targeting IGF-1R (pGFPshIGF-1Rs) in A549 cells and in tumor-bearing mice as compared to lipofection using Lipofectamine 2000. Liposomal magnetofection provided a threefold improvement in transgene expression over lipofection and transfected up to 64.1% of A549 cells in vitro. In vitro, IGF-1R specific-shRNA transfected by lipofection inhibited IGF-1R protein by 56.1±6% and by liposomal magnetofection by 85.1±3%. In vivo delivery efficiency of the pGFPshIGF-1R plasmid into the tumor was significantly higher in the liposomal magnetofection group than in the lipofection group. In vivo IGF-1R specific-shRNA by lipofection inhibited IGF-1R protein by an average of 43.8±5.3%; that by liposomal magnetofection inhibited IGF-1R protein by 43.4±5.7%, 56.3±9.6%, and 72.2±6.8%, at 24, 48, and 72 h, respectively, after pGFPshIGF-1R injection. Our findings indicate that liposomal magnetofection may be a promising method that allows the targeting of gene therapy to lung cancer.

[Biological behaviors and chemosensitivity of NSCLC A549 cells after IGF-IR gene silencing by targeting RNAi in vitro].

OBJECTIVE: To investigate the biological behaviors and chemosensitivity of non-small cell lung cancer (NSCLC) cell line A549 after IGF-IR gene silencing by RNA interference (RNAi) in vitro. METHODS: Two plasmids siRNA 1 and 2 expressing IGF-IR siRNA with human U6 promoter were constructed,and an unrelated siRNA was used as negative control. NSCLC A549 cells were transfected with sequence-specific siRNA or unrelated siRNA as control. Quantitative RT-PCR and Western blot were used to detect the expression of IGF-IR. NSCLC A549 cells were transfected with siRNA and treated with DDP. MTT assay and flow cytometry were used to assess the effects of IGF-IR silencing on tumor cell proliferation and chemosensitivity. RESULT: Transfection of NSCLC cells with siRNA resulted in reduction of IGF-IR mRNA expression by 78.9 % and protein production by 89.8%. The decrease in IGF-IR levels caused significant growth inhibition of A549 cells both at 48 h and at 72 h, and decrease of the IC50 of DDP at 24 h, 48 h and at 72 h. Flow cytometry showed that 77.5% of A549 cells retained in G0/G1 phase. CONCLUSION: The sequence specific suppression of IGF-IR gene expression by RNAi enhances sensitivity to DDP in NSCLC cell.

Knockdown of insulin-like growth factor 1 receptor enhances chemosensitivity to cisplatin in human lung adenocarcinoma A549 cells.

The effects of RNA interference-mediated insulin-like growth factor 1 receptor (IGF1R) gene silencing in response to cisplatin (DDP) in the lung cancer cell line A549 in vivo and in vitro were investigated using two plasmids expressing short hairpin RNA (shRNA) to IGF1R. A549 cells were transfected with plasmids expressing each shRNA and then treated with DDP. Semi-quantitative reverse transcription-PCR and Western blot analysis were used to detect the expression of IGF1R. MTT assay, flow cytometry and tumor growth assay in athymic nude mice were used to assess the chemosensitivity to DDP following IGF1R knockdown. Our data showed that the transfection of A549 cells with shRNA resulted in specific silencing of IGF1R by 78.9% at the mRNA level and by 89.8% at the protein level. Down-regulation of IGF1R significantly enhanced cell sensitivity to DDP, decreased the IC50 of DDP in A549 cells at 24 h, 48 h and 72 h, and retained 77.5% of A549 cells in the G0/G1 phase. Furthermore, shRNA-mediated silencing of IGF1R in combination with DDP treatment enhanced the suppression of tumor growth in both size and weight by more than 60% and increased apoptosis by more than 75% when compared with the controls in vivo. Suppression of IGF1R gene expression by shRNA enhances the chemosensitivity of A549 cells to DDP both in vitro and in vivo, indicating the therapeutic potential of RNA interference as a method for gene therapy in treating lung cancer.

[shRNA-mediated insulin-like growth factor I receptor gene silencing inhibits cell proliferation, induces cell apoptosis, and suppresses tumor growth in non-small cell lung cancer: in vitro and in vivo experiments].

OBJECTIVE: To study the effects of RNA interference (RNAi)-mediated insulin-like growth factor I receptor (IGF-IR) gene silencing on human lung cancer cells. METHODS: Plasmids expressing IGF-IR shRNA1 and IGF-IR shRNA2 were constructed. Human non-small cell lung cancer cells of the line A549 were cultured and transfected with sequence-specific shRNA. RT-PCR was used to monitor the IGF-IR mRNA expression. Western blotting was used to detect the expression of IGF-IR, bcl-2 and caspase-3, associated with apoptosis, and IGF-IR signaling pathways-associated proteins, total and phospho-ERK1/2 and Akt. MTT assay and flow cytometry were used to examine the cell activity and cell cycle. Twelve nude mice were injected subcutaneously with A549 cells, 20 days later the mice were randomly divided into 3 groups to be injected into the tumor with IGF-IR, PBS, or blank plasmid respectively 4 times with the interval of 5 days. Five days after the 4th injection the mice were killed and the tumors were taken out. TUNNEL assay was used to detect the apoptotic cell in the tumor. RESULTS: RT-PCR showed that the IGF-IR mRNA expression level of the A549 cells transfected with IGF-IR shRNA1 was only 24% +/- 4% that of the A549 cells transfected with blank plasmid (P < 0.05); however, the IGF-IR mRNA expression level of the A549 cells transfected with IGF-IR shRNA2 was 78% +/- 5% that of the A549 cells transfected with blank plasmid (P > 0.05). The IGF-IR protein expression level of the A549 cells of the IGF-IR shRNA1 group was only 10.2% +/- 2.8% that of the A549 cells of the blank plasmid group (P < 0.05). Western blotting showed that the protein expression levels of bcl-2 and caspase-3p20 of the A549 cells of the IGF-IR shRNA1 group were 46% +/- 6% and 156% +/- 8% those of the negative controls (both P < 0.05); however, the protein expression levels of bcl-2 and caspase-3p20 of the A549 cells of the IGF-IR shRNA2 group were not different from those of the negative control cells. The Akt kinase and ERK phosphorylation levels of the A549 cells of the IGF-IR shRNA1 group were 10% and 36% +/- 3% those of the negative control cells respectively (both P < 0.05). Since 48h after the transfection the active cell number of the IGF-IR shRNA1 group was 64% +/- 7% that of the negative group (P < 0.05), and this decrease effect lasted to 72 h after (67% +/- 6% that of the negative cells, P < 0.05). 48 h after the transfection the percentage of cells at G(0)/G(1) phase of the IGF-IR shRNA1 group was 77.5%, significantly higher than that of the negative control group, and the percentages of the cells at S and G(2)/M phases of the IGF-IR shRNA1 group were 15.7% and 7.3% respectively, both significantly lower than those of the negative control group (23.0% and 29.9% respectively). Since the second injection the tumor size of the mice of IGF-IR shRNA group was 40% - 50% that of the PBS group (P < 0.05), and the tumor size of the mice of the PBS group was 90% that of the control group. TUNNEL assay showed that the number of apoptotic cells in the tumors of the IGF-IR shRNA1 group mice was 118 +/- 8/high power, significantly higher than that of the control group (70 +/- 9, P < 0.05). CONCLUSION: RNAi technique effectively inhibits the expression of IGF-IR, thus decreasing the NSCLC cell proliferation inducing apoptosis and inhibiting the tumor growth.

Silencing of the type 1 insulin-like growth factor receptor increases the sensitivity to apoptosis and inhibits invasion in human lung adenocarcinoma A549 cells.

The type 1 insulin-like growth factor receptor (IGF-1R), which is over-expressed or activated in many human cancers, including lung cancer, mediates cancer cell proliferation and metastasis. Several studies indicate that blocking IGF-1R expression can inhibit tumor cell proliferation and metastasis. In this study, inhibition of the endogenous IGF-1R by recombinant adenoviruses encoding short hairpin RNAs against IGF-1R was found to significantly suppress IGF-1R expression, arrest the cell cycle, enhance the apoptotic response, and inhibit proliferation, adhesion, invasion and migration in A549 cells. Moreover, silencing IGF-1R decreases the expression of invasive-related genes including matrix metalloproteinase-2 (MMP-2), MMP-9, and urokinase-plasminogen activator (u-PA), and the phosphorylation of Akt and ERK1/2. These results suggest that the silencing of IGF-1R has the potential to be an effective cancer gene therapy strategy for human lung cancer.

Suppression of type 1 Insulin-like growth factor receptor expression by small interfering RNA inhibits A549 human lung cancer cell invasion in vitro and metastasis in xenograft nude mice.

Cancer invasion and metastasis, involving a variety of pathological processes and cytophysiological changes, contribute to the high mortality of lung cancer. The type 1 insulin-like growth factor receptor (IGF-1R), associated with cancer progression and invasion, is a potential anti-invasion and anti-metastasis target in lung cancer. To inhibit the invasive properties of lung cancer cells, we successfully down-regulated IGF-1R gene expression in A549 human lung cancer cells by small interfering RNA (siRNA) technology, and evaluated its effects on invasion-related gene expression, tumor cell in vitro invasion, and metastasis in xenograft nude mice. A549 cells transfected with a plasmid expressing hairpin siRNA for IGF-1R showed a significantly decreased IGF-1R expression at the mRNA level as well as the protein level. In biological assays, transfected A549 cells showed a significant reduction of cell-matrix adhesion, migration and invasion. Consistent with these results, we found that down-regulation of IGR-1R concomitantly accompanied by a large reduction in invasion-related gene expressions, including MMP-2, MMP-9, u-PA, and IGF-1R specific downstream p-Akt. Direct tail vein injections of plasmid expressing hairpin siRNA for IGF-1R significantly inhibited the formation of lung metastases in nude mice. Our results showed the therapeutic potential of siRNA as a method for gene therapy in inhibiting lung cancer invasion and metastasis.

Down-regulation of IGF-IR using small, interfering, hairpin RNA (siRNA) inhibits growth of human lung cancer cell line A549 in vitro and in nude mice.

Type I insulin-like growth factor receptor (IGF-IR), which is frequently overexpressed in a variety of human cancers including lung cancer, mediates cancer cell proliferation and tumor growth. In this study, we used a human U6 promoter-driven DNA-template approach to induce hairpin RNA (hpRNA)-triggered RNAi to silence IGF-IR gene expression in the human lung cancer cell line A549, and then evaluate its effects on apoptosis, apoptosis-related gene expression, and the growth of tumor cells in vitro and in nude mice. IGF-IR expression levels were found to markedly decrease in cells transfected with a plasmid expressing hairpin siRNA for IGF-IR (by more than 78.9%). Down-regulation of IGR-IR concomitantly accompanied reduction of bcl-2 as well as pERK and pAkt levels, activation of caspase-3, apoptosis and growth inhibition of A549 cells in vitro. Direct intratumoral injections of plasmid DNA expressing hpRNA for IGF-IR significantly regressed pre-established tumors in nude mice. Our results support the therapeutic potential of RNAi as a method for gene therapy in treating lung cancer.

Pretreatment with aminophylline reduces release of Troponin I and neutrophil activation in the myocardium of patients undergoing cardioplegic arrest.

OBJECTIVE: Cardioplegic arrest and subsequent reperfusion results in myocardial injury partly related to local inflammation in the heart. It has been proven that aminophylline has numerous anti-inflammatory effects. This study has been designed to evaluate the effects of aminophylline used as a cardioprotective agent for patients undergoing cardiopulmonary bypass (CPB) for valve replacement. METHODS: Thirty patients undergoing elective valve replacement were randomized to receive either aminophylline (n=15), or normal saline (control n=15). Administration of aminophylline (5mg/kg) was injected intravenously after induction of anesthesia. The cardiac Troponin I (cTnI), myocardial myeloperoxidase (MPO) activity, atrial cyclic AMP, and a coronary sinus neutrophil count were measured before and after cardioplegic arrest. RESULTS: There were no differences between the two groups with regard to clinical variables. The cTnI concentration increased significantly after aortic declamping in both groups. However, it was significantly lower, 8h after aortic declamping, in aminophylline group (1.00+/-0.41 vs 2.37+/-1.35 ng/ml p=0.038). The atrial cAMP was significantly higher before aortic cross-clamping in aminophylline group (42.5+/-6.7 pmol/g tissue vs 30.6+/-12.4 pmol/g tissue p=0.04). In addition, we found that the aminophylline group had a significantly lower MPO after reperfusion (1.50+/-0.58 U/g tissue vs 0.86+/-0.24 U/g tissue p=0.003), and a significantly lower neutrophil count 30 min after aortic declamping (0.68+/-0.11x10(3) cell/ml vs 0.32+/-0.16x10(3) cell/ml, p=0.023). CONCLUSIONS: Pretreatment with intravenous aminophylline reduces the subclinical myocardial injury and neutrophil activation in patients undergoing CPB for valve replacement.