Mini-invasive surgical instruments in transaortic myectomy for hypertrophic obstructive cardiomyopathy: a single-center experience with 168 cases.

BACKGROUND: Although septal myectomy is a standard strategy for managing patients with hypertrophic obstructive cardiomyopathy (HOCM) and drug-refractory symptoms, so far, only a few experienced myectomy centers exist globally. Mainly, this can be explained by the many technical challenges presented by myectomy. From our clinical experience, applying the mini-invasive surgical instruments during myectomy potentially reduces the technical difficulty. This study reports the preliminary experience regarding transaortic septal myectomy using mini-invasive surgical instruments for managing patients with HOCM and drug-refractory symptoms; also, we evaluate the early results following myectomy. METHODS: Between March 2016 and March 2019, consecutive HOCM patients who underwent isolated transaortic septal myectomy using the mini-invasive surgical instruments were enrolled in this analysis. Intraoperative, in-hospital and follow-up results were analyzed. RESULTS: We included 168 eligible patients (83 males, mean 56.8 ± 12.3 years). The midventricular obstruction was recorded in 7 (4.2%) patients. All patients underwent transaortic septal myectomy with a mean aortic cross-clamping time of 36.0 ± 8.1 min. During myectomy, 9 (5.4%) patients received repeat aortic cross-clamping. Surgical mortality was 0.6%. Notably, 5 (3.0%) patients developed complete atrioventricular block, they needed permanent pacemaker implantation. The median follow-up time was 6 months; however, no follow-up deaths occurred with a significant improvement in New York Heart Association functional status. We reported a sharp decrease in the maximum gradients from the preoperative value (11.6 ± 7.4 mmHg vs. 94.4 ± 22.6 mmHg, p < 0.001). The median degree of mitral regurgitation fell to 1.0 (vs. 3.0 preoperatively, p < 0.001) with a significant reduction in the proportion of moderate or more regurgitation (1.2% vs. 57.7%, p < 0.001). CONCLUSIONS: Mini-invasive surgical instruments may be beneficial in reducing the technical challenges of transaortic septal myectomy procedure. Of note, transaortic septal myectomy using the mini-invasive surgical instruments may present with favorable results.

High shear stress suppresses proliferation and migration but promotes apoptosis of endothelial cells co-cultured with vascular smooth muscle cells via down-regulating MAPK pathway.

BACKGROUND: Early neointimal hyperplasia of vein graft may be ameliorated via enhancing intravenous surface shear stress. Cellular processes including proliferation, apoptosis and migration of endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) may play very important roles in the process of neointimal hyperplasia of vein graft; and mitogen-activated protein kinase (MAPK) pathways including extracellular signal-regulated kinase (ERK1/2) and p38 pathways play vital roles in regulating a large variety of cellular processes. This study evaluated the impacts of shear stress and MAPK pathways on cellular processes of ECs in a co-culture system with VSMCs, and aimed to test the hypothesis that high shear stress suppresses proliferation and migration but promotes apoptosis of ECs co-cultured with VSMCs via down-regulating MAPK pathway. METHODS: Primary ECs and VSMCs derived from porcine great saphenous vein were collected, respectively. 4-7 generation of cells were used as work cells. ECs and VSMCs were co-cultured and synchronized under high and low shear stress using Parallel-Plate Flow Chamber system. And then, ECs co-cultured with VSMCs were incubated with U0126 (ERK1/2 inhibitor) or PD98059 (p38 inhibitor) under different shear stress. Proliferation, apoptosis and migration of ECs in a co-culture system with VSMCs were detected by 4,5-dimethyl-2-thiazolyl (MTT) assay and bromodeoxyuridine (BrdU) assay, fluorescent-activated cell sorting (FACS) technique, and Transwell assay separately. Each test repeated 3 times. Additionally, protein expressions of ERK1/2 and p38 MAPK were detected by using Western blot, respectively. RESULTS: Under higher level of shear stress condition, proliferation and migration of ECs co-cultured with VSMCs were suppressed, while cell apoptosis was promoted. And blocking ERK1/2 pathway by U0126 or blocking p38 pathway by PD98059, proliferation and migration of ECs co-cultured with VSMCs were further suppressed, while cell apoptosis was further promoted. Additionally, protein expressions of phosphorylation of ERK1/2 and p38MAPK were decreased under higher level of shear stress condition, and were further reduced by blocking ERK1/2 or p38 pathway under shear stress condition. CONCLUSIONS: High shear stress may suppress proliferation and apoptosis of ECs in a co-culture system with VSMCs but promote cell migration via down-regulating ERK1/2 and p38 MAPK pathways.

Patients over 70 years of age with moderate ischemic mitral regurgitation undergoing surgical revascularization plus mitral valve repair: insights from a single-center study of propensity-matched data.

BACKGROUND: Elderly patients, compared with the young, have a higher burden of surgical risk factors with reduced functional capacity and increased comorbidities conditions, and may have worse clinical outcomes. So far, few reports have focused on clinical outcomes of patients over 70 years of age with moderate chronic ischemic mitral regurgitation (IMR) undergoing mitral valve repair at the time of coronary artery bypass grafting (CABG). This single-center study of propensity-matched data attempts to answer a question: compared with patients with age of 70 or less, whether patients over 70 years of age with moderate IMR undergoing CABG plus mitral valve repair receive poor outcomes. METHODS: All eligible patients were included in this study and were entered into either an elderly group (n=142) or a control group (n=182) according to patients' age. In-hospital outcomes (consisting of surgical mortality and major postoperative morbidity) and midterm clinical outcomes (including all-cause mortality and recurrent mitral regurgitation) were compared after propensity score matching (1:1). RESULTS: Using propensity-score matching, 103 pairs of patients were successfully established in a 1:1 ratio. No significant differences between the two matched groups were found with regard to surgical mortality (5.8% vs. 3.9%, P=0.754) and major postoperative morbidity. A total of 184 patients (91 in the elderly group and 93 in the control group) received regular follow-up visit with the median duration of 38 months [interquartile range (IQR), 27-56 months]. There were not any significant differences between the two matched groups regarding overall survival and recurrent IMR-free survival (stratified log-rank P=0.185 and stratified log-rank P=0.453, respectively). The elderly group as compared to the control group did not affect midterm mortality via cox proportional hazard regression (propensity score adjusted hazard ratio, 1.143; 95% confidence interval, 0.761-1.943; P=0.285). CONCLUSIONS: Patients over 70 years of age with moderate chronic IMR undergoing combined CABG and mitral valve repair may receive favorable in-hospital and midterm clinical outcomes.

Impact of severe left ventricular dysfunction on in-hospital and mid-term outcomes of Chinese patients undergoing first isolated off-pump coronary artery bypass grafting.

BACKGROUND: Few studies focused on evaluating the impacts of preoperative severe left ventricular dysfunction on clinical outcomes of patients undergoing off-pump coronary artery bypass grafting surgery (OPCAB). This single center retrospective study aimed to evaluate the impacts of severe left ventricular dysfunction on in-hospital and mid-term clinical outcomes of Chinese patients undergoing first, scheduled, and isolated OPCAB surgery. METHODS: From January 2010 to December 2014, 2032 eligible patients were included in this study and were divided into 3 groups: a severe group (patients with preoperative left ventricular ejection fraction (LVEF) of ≤35%, n = 128), an impaired group (patients with preoperative LVEF of 36-50%, n = 680), and a normal group (patients with preoperative LVEF of >50%, n = 1224). In-hospital and follow-up clinical outcomes were investigated and compared. RESULTS: Patients in the severe group compared to the other 2 groups had higher in-hospital mortality and higher incidences of low cardiac output and prolonged ventilation. Kaplan-Meier curves showed a similar cumulative follow-up survival between the severe group and the impaired group (χ2 = 1.980, Log-rank p = 0.159) and between the severe group and the normal group (χ2 = 2.701, Log-rank p = 0.102). Multivariate Cox regression indicated that grouping was not a significant variable related to mid-term all-cause mortality. No significant difference was found in the rate of repeat revascularization between the severe group (2.4%) and the other 2 groups. CONCLUSIONS: Patients with preoperative LVEF of ≤35% compared to preoperative LVEF of >35% increased the risk of in-hospital death and incidences of postoperative low cardiac output and prolonged ventilation, but shared similar mid-term all-cause mortality and repeat revascularization after OPCAB surgery.

The approach for action recognition based on the reconstructed phase spaces.

This paper presents a novel method of human action recognition, which is based on the reconstructed phase space. Firstly, the human body is divided into 15 key points, whose trajectory represents the human body behavior, and the modified particle filter is used to track these key points for self-occlusion. Secondly, we reconstruct the phase spaces for extracting more useful information from human action trajectories. Finally, we apply the semisupervised probability model and Bayes classified method for classification. Experiments are performed on the Weizmann, KTH, UCF sports, and our action dataset to test and evaluate the proposed method. The compare experiment results showed that the proposed method can achieve was more effective than compare methods.

The complex action recognition via the correlated topic model.

Human complex action recognition is an important research area of the action recognition. Among various obstacles to human complex action recognition, one of the most challenging is to deal with self-occlusion, where one body part occludes another one. This paper presents a new method of human complex action recognition, which is based on optical flow and correlated topic model (CTM). Firstly, the Markov random field was used to represent the occlusion relationship between human body parts in terms of an occlusion state variable. Secondly, the structure from motion (SFM) is used for reconstructing the missing data of point trajectories. Then, we can extract the key frame based on motion feature from optical flow and the ratios of the width and height are extracted by the human silhouette. Finally, we use the topic model of correlated topic model (CTM) to classify action. Experiments were performed on the KTH, Weizmann, and UIUC action dataset to test and evaluate the proposed method. The compared experiment results showed that the proposed method was more effective than compared methods.

[Minimally invasive aortic valve replacement for isolated aortic valve disease: clinical analysis of 101 consecutive patients].

OBJECTIVE: To review the results for minimally invasive aortic valve replacement (AVR) through a 5 cm right anterolateral thoracotomy. METHODS: From July 2009 to September 2011, 101 consecutive patients with isolated aortic valve disease (degenerative in 37 patients, rheumatic in 21 patients, congenital in 37 patients, endocarditic in 3 patients and aorta-arteritis in 1 patients) underwent AVR through the right anterolateral thoracotomy approach in the third intercostal space with a groin incision for femoral connection of cardiopulmonary bypass. The mean age was 45.7 years (ranging from 17 to 71 years). Sixty patients were male. RESULTS: Operations were successfully performed in all but 1 patient (1.0%) who required intraoperative conversion to full sternotomy. Mean duration of cardiopulmonary bypass time and aortic cross-clamp time was (88 ± 24) minutes and (55 ± 18) minutes, respectively. Thirty-day mortality was 1.0% (1/101), this patient was found difficult in weaning off cardiopulmonary bypass and exhibited severe coronary artery plaque, although bypass graft was carried out immediately, the patient died of severe low cardiac output syndrome finally. No blood products were needed in 83.2% patients. Follow-up was performed in all patients at an average of (16 ± 7) months postoperatively. A good recovery was obtained in all patients except one who died of multiple organ failure caused by massive cerebral infarction 38 days after surgery. CONCLUSIONS: Minimally invasive aortic valve replacement though the right anterolateral thoracotomy approach is safe and feasible, with good cosmetic results and rapid postoperative recovery. It is worthy of clinical elective application.

[Repair of posterior mitral valve prolapsed: comparative study of three different approaches].

OBJECTIVE: To compared outcomes of robotic mitral valve repair with those of standard sternotomy, and right anterolateral thoracotomy. METHOD: From August 2010 to July 2011, 70 patients with degenerative mitral valve disease and posterior leaflet prolapsed scheduled for elective isolated mitral valve repair were prospectively nonrandomized to undergo mitral valve operation by standard sternotomy (n = 30), right anterolateral thoracotomy (n = 30), or a robotic approach (n = 10). There were 49 male and 21 female patients, aging from 16 to 70 years with a mean of 53.4 years. Outcomes of the three groups were compared. RESULTS: Mitral valve repair was achieved in all patients except 1 patient in the standard group. There were no in-hospital deaths. The median operation time [(300 ± 41) min, (184 ± 20) min and (169 ± 22) min, F = 112.5, P < 0.01], cardiopulmonary bypass time [(139 ± 26) min, (82 ± 20) min and (69 ± 23) min, F = 36.8, P < 0.01], aortic cross-clamping time [(93 ± 23) min, (47 ± 10) min and (38 ± 8) min, F = 75.0, P < 0.01] were longer for robotic than standard sternotomy and right anterolateral thoracotomy. The robotic group had shortest time of mechanical ventilation time [(4.9 ± 2.1) h, (5.3 ± 4.5) h and (14.1 ± 10.2) h, F = 13.2, P < 0.01], ICU time [(15.1 ± 2.1) h, (16.4 ± 5.4) h and (28.7 ± 16.1) h, F = 11.6, P < 0.01], postoperative hospital stay time [(4.6 ± 1.0) d, (5.7 ± 1.7) d and (8.8 ± 5.1) d, F = 8.0, P < 0.01] with the lowest of drainage [(192 ± 200) ml, (215 ± 163) ml and (405 ± 239) ml, F = 7.1, P < 0.01] and ratio of the patients needed blood transfusion (0, 20.0% and 66.7%, χ(2) = 22.7, P < 0.01). Patients were followed up 6 to 17 months, with 100% completed. No patients died during follow-ups, and no moderate or more mitral regurgitation was observed. The robotic group had the shortest time of return to normal activities compared with the other two groups [(2.4 ± 0.7) weeks, (4.2 ± 1.2) weeks and (8.2 ± 1.8) weeks, F = 83.0, P < 0.01]. CONCLUSION: This study shows mitral valve repair via the right anterolateral thoracotomy and a robotic approach is safe and feasible, with good cosmetic results and rapid postoperative recovery, and is worthy of clinical selective application.

Complications after endovascular repair of Stanford type A (ascending) aortic dissection.

Endovascular treatment has emerged as a less traumatic alternative treatment for several diseases of the thoracic aorta. However, the complications of the endovascular management of ascending aortic dissections are still high. We present a case of two iatrogenic complications after endovascular repair (EVAR) of type A (ascending) aortic dissection. Retrograde aortic dissection at the proximal part of the aortic endovascular graft and a guidewire-induced iatrogenic left ventricular pseudoaneurysm were presented in this patient after the stent-grafting procedure. Fourteen months later, surgical replacement of the ascending aorta and proximal arch was performed and the left ventricular pseudoaneurysm was treated successfully by linear closure. The patient recovered uneventfully. Although aortic endovascular grafting is apparently less traumatic, indications and potential complications related to the stent graft should be considered with great care.

Very low density lipoprotein receptor subtype II silencing by RNA interference inhibits cell proliferation in hepatoma cell lines.

Very low density lipoprotein receptor (VLDLR) belongs to the low density lipoprotein receptor family, it is divided into two subtypes according to forms with an absence (type II) or a presence (type I) of the O-linked sugar domain. VLDLR have been detected in kinds of cancers so far; however, the subtype of VLDLR in hepatocellular carcinoma (HCC) tissues and hepatoma cell lines has yet to be reported. We detected the VLDLR expression in 39 cases of hepatocellular carcinoma and in three kinds of hepatoma cell lines: HepG2, HBV transfected HepG2.2.15, SMMC-7721 and normal human fetal liver cell line LO2 using RT-PCR and western blotting. The results showed that both type I and type II VLDLR were detected in HCC tissues and hepatoma cell lines, and the type II VLDLR expression was significantly higher than that of type I in cell lines. We inhibited the type II VLDLR expression by shRNA-mediated RNA interference in HepG2, SMMC-7721 cell and then subsequently found the cell proliferation slowed down. The cyclinD1 expression confirmed the cell cycle was arrested at the G0/G1 phase, suggesting that inhibiting the type II VLDLR expression may have a positive impact on carcinogenesis of HCC.

[Role of focal adhesion kinase in the hypoxia-induced invasion of SMMC-7721 cells].

OBJECTIVE: To study focal adhesion kinase (FAK) expression in hypoxia-stressed SMMC-7721 cells and the role of FAK expression in the hypoxia-induced invasion of SMMC-7721 cells. METHODS: SMMC-7721 cells were cultured in 21% O2 or 1% O2. FAK expression was determined by Western blot. The siRNA expression vector pshRNA-FAK targeting to FAK and the control vector pGensil-2 were transfected into SMMC-7721 cells. The hypoxia-induced migration and invasion ability of SMMC-7721 cells transfected with pshRNA-FAK were analyzed. In normoxia, invasion of SMMC-7721 cells transfected with pcDNA3-FAK was analyzed. RESULTS: The expression of FAK was increased significantly in SMMC-7721 cells 24 h after hypoxia stress (P<0.01). The level of FAK protein was decreased by 74.6%+/-5.1% after the pshRNA-FAK transfection in normoxia and hypoxia. The migration and invasion of SMMC-7721 cells was increased in 1% O2 (P<0.01). However, the migration and invasion of SMMC-7721 cells transfected with pshRNA-FAK was decreased in 1% O2 (P<0.05). Overexpression of FAK significantly stimulated the invasion of SMMC-7721 cells. CONCLUSION: Up-regulation of FAK may play an important role in the invasion of SMMC-7721 cells induced by hypoxia.

[Hypoxia induces heat shock protein HSP70-2 expression in a HIF-1 dependent manner].

OBJECTIVES: To investigate role of hypoxia inducible factor 1 (HIF-1) in the transcriptional activation of heat shock protein 70-2 (HSP70-2) in hepatocellular carcinoma (HCC) cells under hypoxic conditions. METHODS: HCC cells were exposed to reduced oxygen atmosphere (1% O2), or treated with YC-1 or HIF-1 alpha siRNA, the expression of HIF-1 alpha and HSP70-2 were detected by Western blot analysis. Serial deletions of the HSPA2 promoter were cloned in the reporter pGL3-Basic plasmid. These reporter plasmids were co-transfected with HIF-1 alpha siRNA, and the promoter activities were detected with the dual luciferase assay. RESULTS: Western blot analysis showed that both HIF-1 alpha and HSP70-2 proteins were strongly increased after HCC cells were exposed to hypoxic conditions (1% O2) for 6 h, and the expression level of HSP70-2 was increased in a time-dependent manner. Treatment of HepG2 cells with YC-1 or HIF-1 alpha siRNA significantly inhibited the expression of HIF-1 alpha and HSP70-2. In silico analysis of the HSP70-2 promoter using the Gene2 Promoter software revealed the presence of two putative hypoxic response element (HRE) consensus at -446bp (HRE1) and -238bp (HRE2). Depletion of promoter sequence between -653 and -385 led to a dramatic reduction of promoter activity, whereas further deletion to position -201 did not reduce the activity further. These data suggested that HRE1 plays an important role in hypoxia-induced activation of the HSPA2 promoter. Site-directed mutagenesis further confirmed these results. Mutation of HRE1 but not of HRE2 abrogated the sensitivity of the HSP70-2 promoter to hypoxia. CONCLUSIONS: HSP70-2 expression is up-regulated in response to hypoxia and a HIF-1 binding site (HRE1) in the HSP70-2 promoter is involved in this response.

HBx protein induces expression of MIG and increases migration of leukocytes through activation of NF-kappaB.

Elevated expression of monokine induced by the interferon-gamma (MIG) has been shown in HBV carriers, and it is involved in the infiltration of inflammatory cells and liver damage after HBV infection. However, the molecular mechanisms by which HBV-induced MIG expression have not been characterized. Our results indicated that HBx protein induced MIG expression in a dose-dependent manner. Such increase was due to the direct binding of NF-kappaB to the MIG promoter. By luciferase, chromatin immunoprecipitation and electrophoretic mobility shift assays, we demonstrated that the NF-kappaB binding site at positions -147 was essential for transcriptional activation of MIG promoter by HBx protein. Chemotaxis assay showed that the up-regulation of MIG protein levels enhanced the migration of peripheral blood lymphocytes (PBLs), and inhibition of NF-kappaB significantly decreased the chemotaxis activity. Our findings provide a new insight into how leukocytes migrate to liver, and disclose a new regulatory mechanism of MIG expression after HBV infection.

Transcriptional up-regulation of FoxM1 in response to hypoxia is mediated by HIF-1.

The proliferation-specific Forkhead box M1 (FoxM1) transcription factor is overexpressed in cancer cells and acts as an important regulator of cancer cell growth and survival. Here, we show the molecular mechanisms by which hypoxia regulate FoxM1 expression in cancer cells. When cells were subjected to hypoxia (1% O2), the mRNA and protein levels of FoxM1 had a significant increase in cancer cells (HepG2, MCF-7, and HeLa). Such increase was due to the direct binding of hypoxia-inducible factor 1 (HIF-1) to the HIF-1 binding sites in the FoxM1 promoter. By deletion and mutation assays, we demonstrated that the HIF1-1 and HIF1-3/4 binding sites on the FoxM1 promoter were essential for transcriptional activation of FoxM1 by hypoxia. We also demonstrated that HIF-1alpha directly bound to the promoter of FoxM1 and the binding was specific, as revealed by HIF-1 binding/competition assay and chromatin immunoprecipitation assay. Consequently, the up-regulation of FoxM1 accelerated the growth of hypoxic cancer cells by decreasing nuclear levels of p21 and increasing expression of cyclin B1 and cyclin D1. These findings provide a new insight into how tumor cells overcome hypoxic stress and survive, and also disclose a new regulatory mechanism of FoxM1 expression in tumor cells.

Transcriptional upregulation of HSP70-2 by HIF-1 in cancer cells in response to hypoxia.

Heat shock protein 70-2 (HSP70-2) can be expressed by cancer cells and act as an important regulator of cancer cell growth and survival. Here, we show the molecular mechanisms by which hypoxia regulate HSP70-2 expression in cancer cells. When cells were subjected to hypoxia (1% O2), the expression of HSP70-2 had a significant increase in cancer cells. Such increase was due to the direct binding of hypoxia-inducible factor to hypoxia-responsive elements (HREs) in the HSP70-2 promoter. By luciferase assays, we demonstrated that the HRE1 at position -446 was essential for transcriptional activation of HSP70-2 promoter under hypoxic conditions. We also demonstrated that HIF-1alpha binds to the HSP70-2 promoter and the binding is specific, as revealed by HIF binding/competition and chromatin immunoprecipitation assays. Consequently, the upregulation of HSP70-2 enhanced the resistance of tumor cells to hypoxia-induced apoptosis. These findings provide a new insight into how tumor cells overcome hypoxic stress and survive, and also disclose a new regulatory mechanism of HSP70-2 expression in tumor cells.

[Inhibition of HSP70-2 expression by RNA interference induces apoptosis of human hepatocellular carcinoma cells].

OBJECTIVES: To determine the effect of short hairpin RNA targeting HSP70-2 on the growth and apoptosis of hepatocellular carcinoma (HCC) cells, and to elucidate its possible mechanisms in mitochondria apoptotic pathway. METHODS: Western blot and immunocytochemistry were used to determine the expression of HSP70-2 in HCC cells and normal hepatocytes. HepG2 and Huh-7 cells were cultured and transfected with HSP70-2 shRNA1 and shRNA2. Cell proliferation was examined by MTT. Cell apoptosis and mitochondria membrane potential were determined by flow cytometry. Western blot was used to analyze the expressions of apoptosis related proteins including Bax, Bcl-2, PARP, caspase-9 and caspase-3. RESULTS: HSP70-2 was expressed at high levels in hepatocellular carcinoma (HCC) cells (SNU-449, HepG2, Huh-7, Hep3B) whereas there were very low levels in normal hepatocytes (L02). Using DNA vector-based RNA interference, we found that knockdown of HSP70-2 inhibited the growth of HCC cells through induction of mitochondria-dependent apoptosis. The mitochondria-dependent apoptosis induced by HSP70-2 knockdown was indicated by cytochrome c release from mitochondria, activation of caspase-9 and caspase-3, and loss of mitochondrial potential. Furthermore, knockdown of HSP70-2 resulted in up-regulation of the pro-apoptotic factor Bax and down-regulation of the pro-survival factor Bcl-2. CONCLUSIONS: Our results indicated that HSP70-2 down-regulation induces apoptosis of HCC cells through the mitochondrial apoptotic pathway, highlighting the importance of HSP70-2 in survival of HCC cells and maintenance of liver function.