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Two oxidative degradation impurities of sugammadex sodium have been successfully synthesized under stress conditions and isolated by preparative high performance liquid chromatography, which would be extremely difficult to prepare stochiometrically by conventional methods due to their structural complexity. Characteristic fragmentation pattern observed by mass spectrometry for sugammadex series compounds helped distinguish the two regioisomeric di-sulfoxide impurities. Confirmed by nuclear magnetic resonance analysis, Impurity I was identified as ortho-disulfoxide sugammadex and Impurity II as meta-disulfoxide sugammadex. It is the first time detailed structures of these two impurities are reported. Additionally, HPLC analysis also indicated the observance of these two impurities in long-term stored sugammadex sodium finished pharmaceutical product but absence in three pilot batches of sugammadex sodium drug substance which met ICH requirements. The compounded analysis technique has proven to be successful and reliable, and we hope that it could be well applied to structure identification for other sugammadex impurities and will be beneficial for other researchers focusing on this field.

This study aims at investigating the nonlinear dynamic behavior of rotating blade with transverse crack. A novel nonlinear rotating cracked blade model (NRCBM), which contains the spinning softening, centrifugal stiffening, Coriolis force, and crack closing effects, is developed based on continuous beam theory and strain energy release rate method. The rotating blade is considered as a cantilever beam fixed on the rigid hub with high rotating speed, and the crack is deemed to be open and close continuously in a trigonometric function way with the blade vibration. It is verified by the comparison with a finite element-based contact crack model and bilinear model that the proposed NRCBM can well capture the dynamic characteristics of the rotating blade with breathing crack. The dynamic behavior of rotating cracked blade is then investigated with NRCBM, and the nonlinear damage indicator (NDI) is introduced to characterize the non-linearity caused by blade crack. The results show that NDI is a distinguishable indicator for the severity level estimation of the crack in rotating blade. It is found that severe crack (i.e., a closer crack position to blade root as well as larger crack depth) is expected to heavily reduce the stiffness of rotating blade and apparently result in a lower resonant frequency. Meanwhile, the super-harmonic resonances are verified to be distinguishable indicators for diagnosing the crack existence, and the third-order super-harmonic resonances can serve as an indicator for the presence of severe crack since it only distinctly appears when the crack is severe.

Background Antegrade cerebral perfusion (ACP), including unilateral and bilateral, is most commonly used for cerebral protection in aortic surgery. There is still no consensus on the superiority of the two methods. Our research aimed to investigate the clinical effects of u-ACP and b-ACP. Methods 321 of 356 patients with type A aortic dissection were studied retrospectively. 124 patients (38.6%) received u-ACP, and 197 patients (61.4%) received b-ACP. We compared the incidence of postoperative neurological complications and other collected data between two groups. Besides, we also analyzed perioperative variables to find the potential associated factors for neurological dysfunction (ND). Results For u-ACP group, 54 patients (43.5%) had postoperative neurological complications, including 22 patients (17.7%) with permanent neurologic dysfunction (PND) and 32 patients (25.8%) with temporary neurologic dysfunction (TND). For b-ACP group, 47 patients (23.8%) experienced postoperative neurological complications, including 16 patients (8.1%) of PND and 31 patients (15.7%) of TND. The incidence of PND and TND were significantly different between two groups along with shorter CPB time (p = 0.016), higher nasopharyngeal temperature (p≦0.000), shorter ventilation time (p = 0.018), and lower incidence of hypoxia (p = 0.022). Furthermore, multivariate stepwise logistic regression analysis confirmed that preoperative neurological dysfunction (OR = 1.20, p = 0.028), CPB duration (OR = 3.21, p = 0.002), and type of cerebral perfusion (OR = 1.48, p = 0.017) were strongly associated with postoperative ND. Conclusions In our study, it was observed that b-ACP procedure exhibited shorter CPB time, milder hypothermia, shorter ventilation time, lower incidence of postoperative hypoxia, and neurological dysfunction compared to u-ACP. Meanwhile, the incidence of ND was independently associated with three factors: preoperative neurological dysfunction, CPB time, and type of cerebral perfusion.

Foreign object damage (FOD) is a frequent but dangerous failure of the compressor. Blade tip timing (BTT) is regarded as a promising on-line monitoring method for blades, but it is difficult to obtain the real FOD data in a laboratory environment. This paper proposes a virtual BTT measuremnt method for FOD. Firstly, we establish the dynamic response model of the multi-degree of freedom damped system, and use the modal superposition method to infer its response displacement under the impact of a foreign object. Secondly, we use the Johnson-Cook model to calculate the stress limit of the blade model. Thirdly, finite element analysis is employed to calculate the influence of different impact positions on the blade tip displacement and the blade failure. Finally, we use the Simulink module to simulate the blade vibration displacement signal, and the measurement process according to the principle of tip timing. By this means, the laboratory simulation of BTT measurement under FOD is realized.

Engine compressor blades play important roles in aeroengine operation. They are easily injured by foreign objects due to direct contact with the outside air. Blade tip timing (BTT) is a non-contacting vibration measurement method for rotating blade health monitoring. However, the under sampled problem is an inevitable obstacle in the feature extraction of BTT signal. An alternative feature extraction method called autocorrelation method for asynchronous vibration analysis is proposed in this paper to identify the vibration amplitude and frequency of the under sampled BTT signal simultaneously. Based on the assumption of single frequency vibration, the signals collected by three probes are used to form two equations, and the vibration frequency and amplitude are obtained by solving them. Additionally, the discussion on the probe layout required by the proposed method is conducted. The verification using simulation signal (the noised signal with one frequency component) and experimental signal (signal collected under constant rotating speed) shows that the amplitude and frequency can be accurately extracted by the proposed method.

Leucosceptroids are sesterterpenoids with potent antifeedant and antifungal activities. In this paper, efforts on two synthetic strategies toward stereoselective total synthesis of the leucosceptroid family of natural products are reported. Intramolecular addition cyclization strategy could lead to a stereochemically mismatched core structure, while intermolecular addition/ring-closing metathesis cyclization strategy successfully furnished an advanced common intermediate bearing eight contiguous stereogenic centers, including three tetra-substituted ones, which fully matches all the stereochemistry on the tricyclic framework in leucosceptroid H. Late-stage transformation of this intermediate to leucosceptroid H encountered difficulty in oxidizing the secondary hydroxyl group to a carbonyl group in the target. Instead of the desired oxidation, an interesting tricyclic spiral product originating from a C-C bond cleavage was observed.

Leucosceptroids are sesterterpenoids with potent antifeedant and antifungal activities. An efficient stereoselective construction of the highly congested [5,6,5] tricyclic framework of leucosceptroid H is presented. This framework bearing eight contiguous stereogenic centers, including three tetrasubstituted ones, could serve as a common intermediate for the collective total synthesis of the leucosceptroid family of natural products.

Compressor blades often operate in high temper-ature, high pressure, and heavy load environments. They are in direct contact with the outside air, which causes their life to be severely limited. Blade vibration is an important factor that reflecting the state of the blade. Therefore, effective blade vibration monitoring methods are needed. Blade tip timing (BTT) is a non-contact blade vibration measurement method that has the potential to achieve real-time condition monitoring. However, one of the biggest obstacles to real-time condition monitoring is the once per revolution (OPR) sensor in BTT. Due to the internal environment limitations of aero-engines, installing the OPR sensor in an actual engine is extremely expensive, and it is almost impossible to install the OPR sensor. To solve this problem, the relationship between the blade spacing change (BSC) and the blade vibration is analyzed and the measurement principle of BSC is presented in this study. Based on BSC, we proposed a novel BTT measurement method that does not need the OPR signal. The simulation and experiment are conducted to show the rationality of the proposed method.

The harsh working environment of the compressor hinders the condition monitoring of rotating blades. Blade faults are mostly induced by foreign object damage or high cycle failure due to initial defects. Detecting these failures before blades being broken will not only ensure engine safety but largely reduce repair costs. As a non-contact measurement technique, Blade Tip Timing(BTT) becomes a more popular method recently for health monitoring and fault diagnosis. By analyzing BTT data, many blade vibration parameters could be obtained. In this paper, we discuss how to extract first bend natural frequency, amplitude and static offset from BTT data. Then the change rule of these parameters around blade fault is illustrated. Afterward, a clustering method is employed to combine these parameters. In addition, a test with two faulty blades is introduced and used to verify the effectiveness of the proposed method.

Objective To study the risk factors of oxygenation impairment in patients with type-A acute aortic dissection who underwent total arch replacement with a stented elephant trunk. Methods In this study, 169 consecutive patients were enrolled who were diagnosed with type-A acute aortic dissection and underwent a total arch replacement procedure at the Qilu Hospital of Shandong University between January 2015 and February 2017. Postoperative oxygenation impairment was defined as arterial oxygen partial pressure/inspired oxygen fraction ≤ 200 with positive end expiratory pressure ≥ 5 cm H2O that occurred within 72 hours of surgery. Perioperative clinical characteristics of all patients were collected and univariable analyses were performed. Risk factors associated with oxygenation impairment identified by univariable analyses were included in the multivariable regression analysis. Results The incidence of postoperative oxygenation impairment was 48.5%. Postoperative oxygenation impairment was associated with prolonged mechanical ventilation time, intensive care unit stay, and hospital stay. Multivariable regression analysis demonstrated that body mass index (odds ratio [OR], 1.204; 95% confidence interval [CI], 1.065-1.361; P = .003), preoperative oxygenation impairment (OR, 9.768; 95% CI, 4.159-22.941; P Conclusions Postoperative oxygenation impairment is a common complication of surgery for type-A acute aortic dissection. Body mass index, preoperative oxygenation impairment, preoperative homocysteine, circulatory arrest time, and plasma transfusion were independent risk factors for oxygenation impairment after a total arch replacement procedure.

Blade Tip Timing (BTT) methods have been increasingly implemented for blade health monitoring. However, most of them are based on the prior knowledge that the resonance’s location is known. Since real BTT test usually takes more than ten hours, it’s unrealistic to Figure out every resonance from the measured raw data manually. Furthermore, BTT data analysis suffers from its inherent under-sampled and non-uniform shortcoming. In this paper, we present a simple yet effective method for BTT-based blade health monitoring. The method starts with an automatic resonance recognition, where cross-correlation and Savitzky Golay filter are used to locate the resonance region. Then an adaptively reweighted least-squares periodogram algorithm is designed to identify parameters of the resonant vibration. The effectiveness of the algorithm was tested using both simulation and real test data.

This study aimed to investigate the effect of bone marrow-derived mesenchymal stem cells (BMSCs) on disseminated intravascular coagulation (DIC) model rats and to further explore the underlying mechanism. A rat model of lipopolysaccharide (LPS)-induced DIC was successfully established, as indicated by impaired plasma hemostatic parameters and damaged organ functions in rats. Importantly, pre-treatment with rat allogeneic BMSCs before LPS injection significantly alleviated systemic intravascular coagulation, reduced plasma levels of organ dysfunction indicators and pro-inflammatory cytokines, suppressed fibrin microthrombi formation, ameliorated liver, heart, and renal injuries, and increased 24-hour survival rates in LPS-induced DIC rats. The protection of BMSCs against DIC was in a moderately dose-dependent manner. Further investigation revealed that BMSCs co-cultured with peripheral blood mononuclear cells (PBMCs) significantly inhibited the LPS-stimulated PBMCs proliferation and the release of pro-inflammatory cytokines from PBMCs. Of note, upregulation of immunosuppressive factors including indoleamine 2,3-dioxygenase and interleukin-10, which was induced by interferon-γ, contributed to BMSCs-mediated inhibition of LPS-stimulated PBMCs proliferation. These effects do not depend on the direct cell–cell contact. In conclusion, BMSCs pre-treatment ameliorates inflammation-related tissue destruction in LPS-induced DIC model rats. The protection of BMSCs may be attributed to their anti-inflammatory and immunomodulatory properties, which render BMSCs a promising source for stem cell-based therapeutic approaches in inflammation-related DIC.

Disseminated intravascular coagulation (DIC) is a fatal thrombohemorrhagic disorder. Bone marrow-derived mesenchymal stem cells (BMSCs) are multipotent stem cells that have tremendous therapeutic effect. Our aim was to explore whether the immune mechanisms were associated with BMSCs-afforded protection against DIC. We generated a rat model of DIC by lipopolysaccharide (LPS, 3 mg/kg) injection via the tail vein. In the treatment group, rats were pre-treated with 1 × l03 , 1 × l04 , 1 × l05 , and 1 × l06 allogeneic BMSCs before LPS injection. Blood sample was withdrawn from the abdominal aorta at 0 (before), 4, and 8 h after LPS injection and used for biochemical analyses. After experiments, the mice were sacrificed and their organs were harvested and observed by H&E and PTAH staining. Continuous infusion of LPS into the rats gradually impaired the hemostatic parameters and damaged organ functions. However, pre-treatment with BMSCs dose-dependently improved the hemostatic parameters. Meanwhile, the treatment significantly suppressed the fibrin microthrombi formation and alleviated liver, heart, lung, and renal injuries. Flow cytometry analysis demonstrated that BMSCs pre-treatment inhibited LPS-induced upregulation of CD3+ CD8+ T cells and CD3+ /CD161a+ NKT cells in the peripheral blood. BMSCs pre-treatment reversed the upregualtion of the B-cell population and the percentage of CD43+ /CD172a+ monocytes in the DIC models. Finally, BMSCs pre-treatment decreased the levels of tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-1β (IL-1β), and interleukin-6 (IL-6) and increased the levels of interleukin-10 (IL-10) in LPS-induced DIC models. Pre-treatment with BMSCs can reduce coagulation and alleviate organ dysfunction via peripheral immune responses in LPS-induced DIC rat model. J. Cell. Biochem. 118: 3184-3192, 2017. © 2017 Wiley Periodicals, Inc.

ObjectivesWe sought to explore and create a reliable, convenient, and economic hyperkinetic pulmonary artery hypertension (PAH) model and confirm the exact time of establishing a reversible or irreversible model to serve as a platform for future studies.MethodsWe used a common carotid artery and jugular vein shunt with an anastomosis and cuff to create a hyperkinetic PAH model in rabbits. At 1, 2, 3, 6, and 12 months postoperatively, the systolic pressure, mean pulmonary arterial pressure, and mean arterial pressure were measured by catheterization and the right ventricle hypertrophy index was calculated. Pathologic changes in the small pulmonary arteries were observed with hematoxylin and eosin staining, and the Heath-Edwards classification system was used to evaluate PAH.ResultsThe anastomosis and cuff graft groups both increased in systolic pressure, mean pulmonary arterial pressure (P

BACKGROUND Ethyl pyruvate (EP) is an anti-inflammatory and anti-oxidant agent associated with many diseases. In this study, we evaluated whether EP could attenuate monocrotaline-induced pulmonary arterial hypertension (PAH). METHODS A PAH model was established by subcutaneously injecting a single dose of monocrotaline (60 mg/kg). And then a daily intraperitoneal injection of EP (50 mg/kg) was administered on day 1 to day 28 (preventive EP treatment) or day 15 to day 28 (therapeutic EP treatment). Hemodynamic changes were measured by catheterization, and the right ventricle hypertrophy index, the medial wall thickness, and the medial wall areas were also calculated. Enzyme-linked immunosorbent assay and immunohistochemical analysis were used to determine the serum levels and expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and endothelin-1 (ET-1) in the lung tissue. RESULTS Both preventive and therapeutic EP treatment significantly ameliorated hemodynamic changes and vascular remodeling indicators (all P < 0.05). The serum levels and expression of TNF-α, IL-6, and ET-1 in the lung tissue were also significantly decreased (all P < 0.05). CONCLUSIONS EP ameliorates monocrotaline-induced PAH and reverses pulmonary vascular remolding in rats by inhibiting the release of TNF-α and IL-6 and reducing the expression of ET-1.

ObjectiveThe study objective was to investigate the effect of recombinant human hepatocyte growth factor gene transfection via an endotracheal approach on hyperkinetic pulmonary artery hypertension rabbit models.MethodsThe rabbits with established pulmonary artery hypertension were separated into a gene transfection group (rabbits treated with intratracheal instillation of human hepatocyte growth factor 2 × 109 plaque-forming units coded by replication-defective recombinant adenovirus), an empty vector group, and a control group. Two weeks after endotracheal gene transfection, immunohistochemistry examination and Western blot were used to detect the protein expression of human hepatocyte growth factor. The hemodynamic data were measured, and pulmonary angiography was performed to investigate the pulmonary collateral vessels. The vascular density in lung also was analyzed.ResultsTwo weeks after gene transfection, human hepatocyte growth factor was expressed in the gene transfection group. The mean pulmonary artery pressure in the gene transfection group was lower than in the control and empty vector groups (P

To investigate the reasons behind the seeding difficulty, pollination and embryonic developments of cucumber from crosses of autotetraploid with diploid (4xx4 x , 2xx2x, 4xx2x, 2x×4x) were studied. Results showed: 1) pollen germination rate on the stigma of self-pollinated tetraploid (4x×4x) were the lowest, and in 2x×2x, 2x×4x, the percentage of pollen germination on stigma were higher; 2) tetraploid plant have a higher abnormal embryo sacs rate (from 17.0s to 24.90%) than that of diploid (from 4.8 to 6.5%); 3) the fertilization process of self-pollinated diploid, self-pollinated tetraploid, crosses of tetraploid with diploid (4xx2x) were from 24 to 36 h, from 48 to 60 h, from 36 to 48 h respectively. No fertilization was observed in crosses of diploid with tetraploid (2X×4X). The fertilization rates of self-pollinated tetraploid were lower (19.17 to 25.39%) than that of 4x×2x (30.25 to 48.08%); 4). The embryo developments of self-pollinated diploid and tetraploid were normal, whereas in 4xx2x, the embryo development was abnormal and developed very slowly, which were the key reason of sterility. Therefore, no mature triploid seeds have been obtained; and 5) In 4xx2x, the obvious degeneration of the endosperm was the important factor of the slow embryo development.

ObjectiveTo study the mechanisms of vascular remodeling and increased vascular reactivity, a reliable, economic, easy, and stable animal model of hyperkinetic pulmonary hypertension is needed. The purpose of this study was to construct an animal model of hyperkinetic pulmonary arterial hypertension by chronic systemic–pulmonary shunt in young rabbits.MethodsThoracotomy was performed through a midsternal incision in 1-month-old rabbits, and anastomosis between the left carotid artery and pulmonary artery trunk created a chronic left-to-right shunt. After 3 months, the shunted artery was checked by echocardiography. Systolic, diastolic, and mean pulmonary arterial pressures were measured by microcatheterization. The pathologic changes of small pulmonary arteries were observed after staining with hematoxylin and eosin. Thickness and area indices were calculated.ResultsHigh-flow pulmonary hypertension was successfully established in 24 rabbits 3 months after operation. Relative to a sham operation group, the systolic, diastolic, and mean pulmonary arterial pressures were obviously increased in the experimental group (P

Background Hyperkinetic pulmonary arterial hypertension (PAH) is a common complication in congenital heart disease, and affects operations, indications, and prognoses for patients. Gene-based stem cell transplantation is an alternative treatment that can attenuate PAH. Methods Hyperkinetic PAH rabbit models were successfully established, using common carotid artery and jugular vein anastomosis. Endothelial progenitor cells (EPCs) were isolated from the bone marrow, cultured, and transfected with human hypoxia inducible factor-1 alpha (hHIF-1α), using lentiviruses. Two weeks after the transfected EPCs were transplanted into the rabbits, catheterization was applied to collect hemodynamic data. The hypertrophy of the right ventricle and pulmonary vascular remodeling were evaluated by measuring the right ventricle hypertrophy index, the medial wall thickness, and the medial wall area. Western blot and immunohistochemistry analyses were used to detect the expression of hHIF-1α in the pulmonary small arteries. Results Two weeks after transplantation, systolic pulmonary arterial pressure and mean pulmonary arterial pressure were both attenuated. The hypertrophy of the right ventricle, and pulmonary vascular remodeling were reversed. Expression of hHIF-1α in the hHIF-1α–transfected EPCs that had been transplanted was high, and the number of pulmonary small arteries had increased. In addition, combined HIF-1α and homogeneous EPC therapy was more effective at attenuating PAH and increasing the density of pulmonary small arteries, compared with EPC transplantation alone. Conclusions Both the therapy with HIF-1α–transfected EPCs, and EPC transplantation, attenuated shunt flow–induced PAH, by means of an angiogenic effect. The former therapeutic method was more effective.

The possibility of endothelial nitric oxide synthase (eNOS) gene transfer, which prevents restenosis of vein grafts, was explored in 16 goats. The recombinant adenoviral vector coding endothelial nitric oxide synthase (AdCMVeNOS) and adenoviral vector (AdCMV) were constructed. A total of 6 cm jugular vein was removed, cut into two equal lengths for vein grafts, and infected with AdCMVeNOS or AdCMV in vitro. One segment (2 cm) of each carotid artery was removed. The vein graft that had been infected with AdCMVeNOS was anastomosed to the right carotid artery, and the vein graft that had been infected with AdCMV was anastomosed to the left. The functional expression of eNOS in vein grafts was assessed by the immunohistochemical staining and measurement of NO concentration. The inhibition of intimal hyperplasia in vein grafts was evaluated by the assay of 3H-TDR incorporation, histologic analysis, measurement of intimal thickness, and percent area stenosis. Adenovirus mediated eNOS gene transfer to goat vein grafts resulted in functional transgene expression with increased NO release. Increased local NO production could inhibit intimal hyperplasia and increase the patent rate of vein grafts.

Aims Growing evidence suggests a close association of plaque angiogenesis with atherosclerotic plaque formation and progression, and an important role of matrix metalloproteinase (MMP) in angiogenesis and atherosclerosis. We attempted to investigate the functional involvements of MMP8 in angiogenesis. Methods and results Knockdown of MMP8 in human umbilical vein endothelial cells (HuVECs) with MMP-8 shRNA lentivirus resulted in a decrease in in vitro capillary-like network formation, cell proliferation and migration, and impaired its capacity of in vivo angiogenesis. Less nuclear accumulation of β-catenin and lower β-catenin target gene expression levels was observed in the HuVECs expressing lower levels of endogenous MMP8. Knockdown of endogenous MMP8 in HuVECs down-regulated platelet/endothelial cell adhesion molecule-1 (PECAM-1) expression by converting less angiotensin I to II, which is an inducer for PECAM-1 gene expression. Aortic rings isolated from MMP8−/−/apoE−/− mice had less endothelial cell sprouting, and endothelial cells in MMP8−/−/apoE−/− mice had a lower ability to migrate into Matrigel plugs and less capacity of proliferation and angiogenesis. Moreover, immunohistochemical analyses revealed that MMP8 was expressed in microvessels within human atherosclerotic plaques and aneurysm. Finally, analyses of MMP8−/−/apoE−/− and MMP8+/+/apoE−/− mice fed a Western diet for 12 weeks showed that MMP8-deficient mice had small lesion size and less endothelial cells within atherosclerotic lesions. Conclusion We demonstrated for the first time that MMP8 plays an important role in angiogenesis in vitro and in vivo . Our findings provide new insights into the molecular mechanisms of plaque angiogenesis and suggest that MMP8 is a potential therapeutic target of cardiovascular diseases.

Although many studies have evaluated the impacts of obesity on various medical treatments, it is not known whether obesity is related to late mortality with implantation of small aortic prosthesis. This study evaluated the effect of obesity on late survival of patients after aortic valve replacement (AVR) with implantation of small aortic prosthesis (size ≤ 21 mm).From January 1998 to December 2008, 536 patients in our institution who underwent primary AVR (307 patients with smaller prostheses) survived the 30 days after surgery. Patients were categorised as normal weight if body mass index (BMI) was ≤ 25 kg/m(2), as overweight if BMI 25-30 kg/m(2), and as obese if BMI ≥ 30 kg/m(2). Data were collected at the third-month (M), sixth-M, first-year (Y), third-Y, fifth-Y, and eighth-Y after operation.By multivariable analysis, obesity was a significant independent factor of late mortality (hazard ratio [HR]: 1.59; p=0.006). The obese and overweight groups of patients exhibited lower survival (p0.001) and a higher proportion in NYHA class III/IV (p0.01) compared with the normal group. Lower EOAI and higher left ventricular mass index were found in the obese and overweight groups, but we saw no significant variance in LVEF among the three groups.Obesity was associated with increased late mortality of patients after AVR with implantation of small aortic prosthesis. Being obese or and overweight may also affect the NYHA classification, even in the longer term.

Hyperkinetic pulmonary arterial hypertension (PAH) severely influences the success of operation for congenital heart disease and deteriorates the prognosis of disease. Adipose-derived stromal cell (ADSC) is a good alternative multipotent stem cell for regeneration medicine. PAH rat models were established by arteriovenous shunt and ADSCs were isolated, cultured, and labeled in vitro. Twelve weeks after shunt operation, rats received an injection of 5 × 10(7) ADSCs. Two weeks after transplantation, hemodynamic abnormality induced by the shunt flow and the hypertrophy of right ventricle were reversed, which was confirmed by invasive measurement and echocardiography examination. The PAH rats receiving cell transplantation demonstrated decreased remodeling of small arteries in the lung; immunohistochemistry analysis showed augmented expression of hepatocyte growth factor (HGF) and increased number of pulmonary small arteries. Western blot and real-time reverse transcriptase-polymerase chain reaction indicated that the protein and mRNA levels of HGF and endothelial nitric oxide synthase increased, respectively, in the lung after cell transplantation. Our results suggested that ADSC transplantation can ameliorate PAH induced by shunt flow by enhancing the expression of HGF and subsequently promoting angiogenesis in the injured lung tissue.

This study was designed to investigate the role of C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) during allograft adventitial inflammation and arteriosclerosis. Lewis rats were used as donors and Wistar rats as recipients for the experimental groups, while both donors and recipients were Wistar rats in the control groups. The 36 experimental and 16 control allografts were divided into four groups (nine in each experimental and four in each control group): group A animals were euthanized at 1 week posttransplantation; groups B, C, and D animals were euthanized at 2, 3, and 4 weeks posttransplantation, respectively. The method of enzyme-linked immunosorbent assay (ELISA) was used to test serum levels of CRP, IL-6, and TNF-alpha. Immunohistological and pathological studies were performed to evaluate allograft adventitial inflammation, arteriosclerosis, and expression of proliferating cell nuclear antigen (PCNA). Allografts collected from group D demonstrated abundant infiltration of smooth muscle cells and collagenous fibers with inflammatory cells in the adventitia. ELISA demonstrated a higher levels of CRP, IL-6, and TNF-alpha in experimental than control groups. Additionally, PCNA increased over time in the adventitia. Our results suggested that the expressions of CRP, IL-6, and TNF-alpha play important roles during the development of allograft adventitial inflammation and arteriosclerosis.

Nitric oxide, a potent vasodilator with an important role in the regulation of pulmonary vascular tone, is synthesized by a family of nitric oxide synthases. To determine whether endothelial nitric oxide synthase (eNOS) gene transfer may prevent pulmonary hypertension, the effects of transfer of the eNOS gene to the lung were studied in rabbits with pulmonary hypertension induced by high pulmonary blood flow.Adenoviral vector encoding the eNOS gene was intratracheally transfected into the lung of rabbits with flow-induced pulmonary hypertension. Rabbits instilled intratracheally with adenoviral vector without encoding the eNOS gene served as a control group. Hemodynamic data were recorded before and after transfection, and transgene expression was investigated.Pulmonary hypertension was significantly attenuated in eNOS gene-transfected rabbits compared with control animals (mean pulmonary arterial pressure, 22.3 +/- 5.5 versus 41.0 +/- 6.9 mm Hg; pulmonary vascular resistance, 326 +/- 42 versus 618 +/- 66 dynes x s x cm(-5); p0.01). Systemic arterial pressure and systemic vascular resistance were unaffected. There was an increase in calcium-dependent conversion of L-arginine to L-citrulline in the lung (16.81 +/- 0.72 versus 4.11 +/- 0.41 pmol x mg protein(-1) x h(-1)) and cyclic guanosine monophosphate levels (0.138 +/- 0.015 versus 0.065 +/- 0.003 pmol/mg protein). Immunohistochemical staining showed expression of the eNOS gene was detected mainly in endothelial cells of small pulmonary vessels. Transgene expression was confirmed using Western blot analysis.These data suggest that intratracheal adenoviral-mediated eNOS gene transfer can attenuate flow-induced pulmonary hypertension in rabbits and may represent a new form of therapy for the treatment of flow-induced pulmonary hypertension.

Background Severe pulmonary hypertension is a common complication of congenital cardiac defects with large left to right shunt, and the closure of a large ventricular septal defect (VSD) with elevated pulmonary vascular resistance (PVR) is associated with significant morbidity and mortality. A unidirectional monovalve homologous aortic patch was designed to close the large VSD with severe pulmonary hypertension in an effort to decrease the morbidity and mortality. Methods Twenty-seven patients (mean age, 15.0 ± 5.6 years) with large VSD with severe pulmonary hypertension (pulmonary vascular resistance, 15.2 ± 3.8 Wood units) were repaired with a unidirectional monovalve homologous aortic patch. According to body surface area and the preoperative arterial oxygen saturation, the monovalve homologous aortic patches were fenestrated on the aortic wall with a diameter of 4 to 8 mm. Results Two patients died of pulmonary hypertensive crisis and cardiac arrest postoperatively. All of the survival patients were followed up (5 months to 10 years) and the cardiopulmonary function was well improved with no late death. Obvious opening and closing of the monovalve was detected by early postoperative echocardiography in seven patients. A small amount of right to left shunt was detected in three patients three months after operation, and in two of them the shunt still existed three years after operation. Conclusions Closure of a large VSD in patients with severe pulmonary hypertension could be performed with low morbidity and mortality when a unidirectional monovalve homologous aortic patch was used and the long-term result was satisfactory.

Kai Liu1*, Guangqing Cao1*, Xiquan Zhang1, Ruifang Liu2, Weiwei Zou3, Shuming Wu11Departments of Cardiovascular Surgery, 2Anesthesia, Qilu Hospital of Shandong University, Jinan; 3The School of Pharmaceutical Science, Shandong University, Jinan, Shandong, People’s Republic of China; *Kai Liu and Guangqing Cao contributed equally to this work.Purpose: Poly lactic-co-glycolic acid nanoparticles (PLGA-NP) are widely used as a biodegradable biomaterial in medicine. Rapamycin-eluting stents have been used for prevention of restenosis during surgery. This study investigated the effect of pretreatment with intraluminal perfusion of carbopol-encapsulated rapamycin-loaded PLGA nanoparticles (RAP-PLGA-NP) on neointimal hyperplasia in a rabbit vein graft model.Methods: A segment of common carotid artery was replaced with a segment of external jugular vein in 60 rabbits which were then separated into four treatment groups, ie, Group 1, in which vein grafts were pretreated with intraluminal RAP-PLGA-NP perfusion, Group 2 in which vein grafts underwent equivalent empty vehicle (PLGA-NP) perfusion, Group 3, in which vein grafts received no treatment, and Group 4, which served as a sham operation group receiving normal vein contrast. On postoperative day 28, the grafts and normal veins were harvested for histologic examination, flow cytometry analysis, and high-performance liquid chromatography measurement.Results: Compared with Group 1, the intima of the grafts were thickened, the ratio of intimal area to vessel area increased, and the collagen volume index of the vein grafts increased significantly in Groups 2 and 3. The cell proliferation index in Group 1 (21.11 ± 3.15%) was much lower than that in Group 2 (30.35 ± 2.69%) and in Group 3 (33.86 ± 8.72%). By high-performance liquid chromatography measurement, retention of rapamycin was detected in Group 1 (11.2 ± 0.37 µg/10 mg) 28 days after single drug perfusion.Conclusion: Pretreatment with intraluminal RAP-PLGA-NP perfusion may inhibit neointimal hyperplasia in vein grafts by penetrating into local tissue and limiting cell proliferation.Keywords: autograft, stenosis, jugular vein, transplants

Background Whether obesity is related to late mortality with implantation of small aortic prosthesis remains to be clarified. This study was aimed to evaluate the effect of obesity on late survival of patients after aortic valve replacement (AVR) with implantation of small aortic prosthesis (size ≤ 21 mm). Methods From January 1998 to December 2008, 307 patients in our institution who underwent primary AVR with smaller prostheses survived the 30 days after surgery. Patients were defined as normal if body mass index (BMI) was 2, as overweight if BMI 24–27.9 kg/m2, and as obese if BMI ≥ 28 kg/m2. Data of New York Heart Association (NYHA) functional classification, left ventricular ejection fraction (LVEF), effective orifice area index (EOAI), and left ventricular mass index (LVMI) of the patients collected at the 3rd month (M), 6th M, 1st year (Y), 3rd Y, 5th Y, 8th Y after operation respectively. Results By multivariable analysis, obesity was an independent factor of late mortality (hazard ratio [HR]: 1.62; P = 0.01). The obesity and overweight group had more poor survival (p Conclusions Obesity was associated with increased late mortality of patients after AVR with implantation of small aortic prosthesis. Being obese or and overweight may also affect the NYHA classification, even in the longer term. EOAI should be improved where possible, as it may reduce late mortality and improve quality of life in obese or overweight patients.