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TWIST1 is an important basic helix‐loop‐helix protein linked to multiple physiological and pathological processes. Although TWIST1 is believed to be involved in vascular pathogenesis, its effects on homeostasis of smooth muscle cells (SMCs) remain poorly understood. Here, we show that TWIST1 protein levels were significantly elevated during SMC phenotypic switching in vivo and in vitro. TWIST1 overexpression promoted phenotypic switching of SMCs, while siRNA targeting of TWIST1 prevented cell transition. Mechanistically, TWIST1 decreased the level of microRNA‐143/145, which governs smooth muscle marker gene transcription. In addition, TWIST1 repressed p68 mRNA and protein expression, a crucial modulator of SMC behavior and microRNA biogenesis. Our co‐immunoprecipitation assay demonstrated a previously unrecognized molecular interaction between TWIST1 and p68 protein. Finally, we found that TWIST1 triggered SMC phenotypic switching and suppressed microRNA‐143/145 expression by promoting the proteasomal degradation of p68. These data suggest a novel role of TWIST1 in the regulation of SMC homeostasis by modulating p68/microRNA‐143/145 axis., Increased TWIST1 expression leads to the suppression of the DDX5/microRNA‐143/145 pathway in VSMC, which induces phenotypic switching of VSMC and promotes the progression of vascular remodeling. Therefore, TWIST1 might be a attractive therapeutic target for inhibiting phenotype‐related vascular disorders.

Lilium shenxianjui Y.L.Xu & Y.F.Lu, a new species of Liliaceae from Zhejiang, East China, is described with illustrations. The new species is morphologically similar to L. concolor and L. bakerianum in having campanulate flowers and converging stamens, but differs from the former in having stems dark purple (vs. green, rarely base purple), leaf blades densely papillose at margin and abaxial mid-ribs (vs. glabrous), pedicle base with 2 bracts (vs. solitary), flowers red-orange, 4–10 in a short raceme (vs. dark red, 1–5 in a raceme or sub-umbel), tepals 4.8–6 cm long, 0.8–1.5 cm wide (vs. 2.2–4 cm long, 4–7 mm wide), nectars glabrous at margin (vs. papillose at margin), anthers lunate, ca. 1 cm long (vs. long-oblong, ca. 7 mm long), styles ±2 as long as ovaries (vs. slightly shorter). It differs from Lilium bakerianum in having pedicle base with 2 bracts (vs. solitary), flowers 4–10, red-orange, unspotted (vs. flowers 1–3, white, purple-red spotted), tepals 4.8–6 cm long, 0.8–1.5 cm wide (vs. 6.5–8 cm long, 1.4–2.3 cm wide), ovaries 8–10 mm long (vs. 1.7–2 cm long).

Growing evidence has shown that apelin/APJ system functions as a critical mediator of cardiac development as well as cardiovascular function. Here, we investigated the role of apelin in the cardiomyogenic differentiation of mesenchymal stem cells derived from Wharton's jelly of human umbilical cord in vitro. In this research, we used RNA interference methodology and gene transfection technique to regulate the expression of apelin in Wharton's jelly-derived mesenchymal stem cells and induced cells with a effective cardiac differentiation protocol including 5-azacytidine and bFGF. Four weeks after induction, induced cells assumed a stick-like morphology and myotube-like structures except apelin-silenced cells and the control group. The silencing expression of apelin in Wharton's jelly-derived mesenchymal stem cells decreased the expression of several critical cardiac progenitor transcription factors (Mesp1, Mef2c, NKX2.5) and cardiac phenotypes (cardiac α-actin, β-MHC, cTnT, and connexin-43). Meanwhile, endogenous compensation of apelin contributed to differentiating into cells with characteristics of cardiomyocytes in vitro. Further experiment showed that exogenous apelin peptide rescued the cardiomyogenic differentiation of apelin-silenced mesenchymal stem cells in the early stage (1-4 days) of induction. Remarkably, our experiment indicated that apelin up-regulated cardiac specific genes in Wharton's jelly-derived mesenchymal stem cells via activating extracellular signal-regulated kinase (ERK) 1/2 and 5.

Objective To investigate the safety and efficacy of transplantation of allogeneic Wharton' jelly-derived mesenchymal stem cells (WJMSCs) in a porcine model of chronic ischemia cardiomyopathy. Methods Cardiomyopathy models (CIMP) were reproduced in 25 minipigs out of 29 by left anterior descending coronary artery balloon occlusion, and the 4 remains served as sham group. The left ventricular ejection fraction (LVEF) was detected by echocardiography, and the value ≤45% was defined as successful modeling. Of that 25 minipigs, 5 died, 3 failed of modeling and 17 remains were successfully modelled. The dose safety experiment of WJMSCs transplantation was firstly performed in 3 successful models and 3 failed models. Three doses were teste d in turn at 6×106, 1×107 and 2×107 with 1 successful and 1 failed model for each dose, and TIMI 3 was considered safety dosage. The remainder 14 CIMP models were randomly assigned to transplantation group and control group (7 each), and given 2×107 WJMSCs intracoronary infusion or equal amounts of normal saline respectively. Echocardiography, histopathology and immunofluorescence tests were performed 8 weeks after WJMSCs transplantation. Results LVEF increased by 11.6% (P

Objective To explore the relationship between symptom-onset-to-balloon time and in-hospital mortality in patients with ST elevation myocardial infarction (STEMI). Methods Since October 2010, all cardiovascular intervention procedures in military hospitals were registered online, including coronary interventions. Data in this study were originated from this registry database. Primary endpoint was in-hospital mortality, and it was stratified by age and infarction location to explore the effects of these factors on the mortality rate. Results 8878 STEMI patients from 92 military medical centers were enrolled in this study. These patients were divided into 3 groups by the length of onset-to-vessel opening time: interval ≤3h (n=2999), interval between 3 and 6h (n=2369), and interval >6h (n=3510). The in-hospital mortality rate in those groups was 2.5%, 2.9% and 3.0%, respectively (P=0.405). In interval ≤3h group, mortality rate in young (70 years) patients with anterior MI was as high as 7.4% (P

A single-line bidirectional optical add-drop multiplexer is proposed to provide ring-based passive optical network with a self-healing functionality to eliminate the effect of any one fiber failure.

It is an important strategic choice for countries to develop low-carbon economy while dealing with climate change. The paper gives a forecast and analysis on population, economic development, technology, energy consumption and CO2 emissions variation in China before 2020 as setting the year 2007 as the base year by using IPAT model. Three scenarios of CO2 emissions are set including business as usual (BAU), energy efficiency improvement scenario (EEI), and low carbon scenario (LC). The result shows that the LC scenario is the most appropriate and the most feasible scenario for China to achieve the low-carbon development in the future. Assuming that China’s future development follows the LC scenario, we give three suggestions of low-carbon transformation in China: technological innovation, energy structure optimization and policy advice.

Rainfall is one of the most important factors of the slope stability. After the "5.12" earthquake, there are a large number of loose solid produced by earthquake on the mountain, which leads to the soils strength loss in the earthquake disaster zones. and induces landslides and collapses easily in the heavy rainfall condition. The soil parameters obtained from the tests, the scene investigation of the Erman mountain landslide of Han Yuan County, the new developed control of ArcGIS to obtain intuitive landslide warning graphs have been carried out. Results show that the picture of hazard grade is consistent with the actual situation of landslide on Erman mountain. It will provide a scientific way to analyze the influence of heavy rainfall on slope stability.

The geological disaster is one of the important research contents of the field of Earth Science. In this paper, the method of theoretical knowledge,field surveys and laboratory experiments is adopted.The Erman Mountain in Hanyuan County is the research object.Analysis the environmental conditions,development characteristics and mechanism. Select the characters of landslide, geological structure, elevation, slope, slope, earthquake, rainfall and other factors as analysis variables. Combine GIS with fuzzy mathematical evaluation method, develop the landslide stability evaluation plug-in and then divide the risk regionalization of study area, in order to avoid occurrence of geological hazards in the area, reduce casualties and property losses. The results show that The occurrence of landslide areas are mainly concentrated in the elevation at about 1600 m and 30° ~ 50° slope area.With the increase of height and slope, the possibility of landslides is increasing.

Objective To explore the influence of apelin-13 on 5-azacytidine (5-Aza) inducing differentiation of human umbilical cord mesenchymal stem cells (hUC-MSCs) to cardiomyocytes. Methods hUC-MSCs were cultivated by tissue adherent method, and subcultured after digested with trypsin. The second passage cells (P2) were cultured for 14 days with different concentrations of apelin-13 (0, 1×10–6mol/L, 2×10–6 and 10×10–6mol/L apelin-13, called as group A, B, C and D respectively), and the concentration of 5-Aza was 10×10–6mol/L in each group. Immune markers on the surface of hUC-MSCs were detected by flow cytometry, the absorbance (A value) of cultured cells at 570nm was detected by MTT method, the mRNA expression levels of troponin T (cTnT) and GATA-4 were determined by RT-PCR, and the expression of cTnT (myocardial cell surface marker) was observed by immunohistochemistry. Results HUC-MSCs expressed CD44, CD90, CD105, CD73 and HLA-ABC, but did not express CD34, CD45 or HLA-DR. The A value at 570nm of hUC-MSCs treated with 10×10–6mol/L apelin-13 was 0.875±0.325 and similar to that of hUC-MSCs treated with 0 mol/L apelin-13 (0.841±0.290, P>0.05). The expression levels of cTnT mRNA and GATA-4 mRNA in groups B, C and D were 2.09±1.35, 5.24±1.30 and 1.17±0.63 and 2.68±1.18, 4.82±0.14 and 2.14±0.27 times those in group A. The expression levels of cTnT and GATA-4 mRNA in group C were significantly higher than those in groups B and D (P

The cardiac lineage arises from the cardiogenic area located in anterior lateral plate mesoderm during gastrula stage. Differentiation of cells in cardiac mesoderm into cardiac progenitor cells was regulated by complex signaling networks involving specific cytokines, inducing signal proteins and the core cardiac transcription factors. Any link of signaling networks influenced by mutation in genetics and changes in environment would lead to a series of congenital heart defects. Therefore, studies of signal transduction mechanism in heart development will give rise to a series of significant theoretical and clinical contributions to the mechanism of development of congenital heart diseases. Recently, it has been proved that a group of early transcription factors, including Nkx2.5, GATA4, Tbx5 and Isl-1, were involved in the complicated signaling networks during heart development. However, the mechanism of most signaling pathways in the networks remains unclear. In the present paper, the recent progresses concerning cardiac progenitor cells, a group of transcription factors, including Nkx2.5, GATA4, Tbx5, Isl-1 and Apelin/APJ pathways, were discussed. DOI: 10.11855/j.issn.0577-7402.2013.11.019

Compressive sensing (CS) is an emerging technology which can capture and represent compressible signal at a rate below the Nyquist rate of sampling. In this paper, the perceptual compressive sensing scheme is proposed. Firstly, two-dimentional Discrete Wavelet Transform (DWT) is applied for sparse representation and the perceptual feature is calculated for the different wavelet coefficient. Then the coefficients are partitioned into four blocks. According to the perceptual features, the perceptual weighted CS measurement is performed for different block respectively. Experimental results show that the proposed scheme achieves higher subjective and objective performance compared with the algorithm without the human vision system. With 40% coefficients retained, the image can still be recovered with considerably objective and subjective quality.

The previous models of automobile short-term demand were mainly for single time series. For this disadvantage, the definition of extensive correlation evaluation was proposed, and then the method was discussed to reflect the correlation of factors on automobile demand. Utilizing extensive skills, factors and sub-factors were represented as correlation eigenmatrix which could ensure the level of each factors influences on automobile demand. Accordingly, short-term demand predictive model of automobile was established based on continuous time model.

Objective: Obesity is a prominent component of metabolic syndrome and a major risk factor for renal disease. The aim of this study was to explore the effect of cross-talk between peroxisome proliferator-activated receptor (PPAR)δ and p38 mitogen-activated protein kinase (p38 MAPK) on obesity-related glomerulopathy. Design and Methods: Male Wistar rats were randomly assigned to standard laboratory chow or a high-fat diet for 32 weeks. Glomerular mesangial cells HBZY-1 and mature differentiation 3T3-L1 cells were cocultured and were transfected with PPARδ-expressing vectors or treated with agonist or inhibitor of PPARδ or p38 MAPK. Results: Rats on a high-fat diet showed typical characteristics of metabolic syndrome including obesity, dyslipidemia, insulin resistance, and hypertension. Rats on a high-fat diet also had significant glomerular hypertrophy and extracellular matrix accumulation, which were accompanied by increased p38 MAPK phosphorylation and decreased PPARδ expression in the kidney tissue. The roles of p38 MAPK and PPARδ in a coculture system of mesangial cells and mature differentiation 3T3-L1 cells were further explored. PPARδ suppression promoted laminin and type IV collagen secretion through p38 MAPK phosphorylation in mesangial cells, whereas PPARδ overexpression or PPARδ agonist attenuated phosphorylation of p38 MAPK and laminin and type IV collagen secretion. Conclusions: The characteristics of obesity-related glomerulopathy, which might be partly caused by PPARδ suppression-induced p38 MAPK activation and laminin and type IV collagen secretion was demonstrated.

Our previous study demonstrated that the apelin–APJ pathway contributed to myocardial regeneration and functional recovery after bone marrow-derived mesenchymal stem cell (BM-MSC) transplantation during the differentiation of BM-MSCs into cardiomyogenic cells in acute myocardial infarction (AMI) rat models. However, the underlying mechanisms by which apelin promotes cardiac repair and functional recovery have not been completely clarified. In the present study, we investigated whether apelin could mobilize and activate endogenous cardiac stem cells and progenitors, thereby mediating regeneration and repair of the myocardium after AMI in rat models. Six-week-old male Sprague–Dawley rats underwent AMI and received apelin-13 (200 ng, n = 10) or an equivalent volume of saline by intramyocardial injection ( n = 10); there was also a sham operation group ( n = 8). Proliferation of endogenous cardiac stem cells was analyzed by immunofluorescence staining in rat infarcted myocardium, and heart function was evaluated by echocardiography at 28 days after apelin-13 injection. Treatment with apelin-13 led to a significant increase of Ki-67 + -c-kit + /Sca-1 + /Flk-1 + endogenous cardiac stem or progenitor cells in the border zone and infarct zone of rat hearts at 28 days after myocardial infarction (MI). Significant increases in the expression of c-kit, Sca-1, and Flk-1 on both levels of transcription and translation were confirmed by real-time polymerase chain reaction (RT-PCR) and Western blot. Treatment of apelin-13 also resulted in a significant reduction of infarct size and improvement of cardiac function post-MI. We conclude that apelin-13 is able to enhance mobilization, survival, and proliferation of endogenous myocardial stem cells in the injured heart, providing a novel mechanistic explanation for how apelin-13 might repair the heart and improve cardiac function. Thus, apelin-13 or pharmacological agonists of the APJ receptor could act as novel therapies for heart regeneration.

Objective To illustrate the relationship between abdominal fat accumulation and cardiac remodeling in hypertension patients. Methods Visceral fat area (VA) and substantial fat area (SA) were assessed by CT in 380 hypertensive patients (male 198, female 182) with an age range of 21-83 years during the period of Jan 2006 to Dec 2008, and their blood pressure, waist circumference (WC), body mass index (BMI), interventricular septum thickness (IVST) were measured at the same time. The patients were divided into 4 groups according to their VA and WC, namely visceral fat obesity (VFO), pseudo-VFO, masked visceral fat obesity (MVFO), and non-obesity; intra-abdominal fat normal group (VA normal), intra-abdominal fat accumulation group (IFA); interventricular septum thickening group, and normal group. The differences in IVST, SA, VA, VA/ SA, WC and BMI were observed between the groups. Results The values of WC, VA, BMI, VA/SA were significantly higher in interventricular septum thickening group than in normal group, while the SA was significantly lower than that in normal group, and the difference was statistically significant (P < 0.05). IVST, WC, BMI, VA and VA/SA were significantly higher in IFA group than in VA normal group, while SA was obviously higher in VA normal group, and showed statistically significant difference (P < 0.05). IVST and VA were significantly higher in VFO group than in other groups (P < 0.05), and the VA/SA was significantly lower in VFO group than in MVFO group (P < 0.05); the IVST and VA in MVFO group were significantly higher than those in pseudo-VFO group and non-obesity group (P < 0.05). The SA in pseudo-VFO group was significantly higher than that in VFO, MVFO and non-obesity groups (P < 0.05), however, there was no statistically significant difference in IVST when compared with non-obesity group. Logistic correlation analysis showed VA/SA, VA and WC were the risk factors leading to ventricular septal hypertrophy. Conclusions Masked abdominal obesity is significantly related to septal hypertrophy in hypertension, and VA/SA is an important risk factor for ventricular septal hypertrophy.

Objective To investigate the clinical application and its influencing factors of ankle-brachial index (ABI) and toe-brachial index (TBI) in the diagnosis of arterial disease of lower extremity. Methods ABI and TBI were measured in 800 limbs of 402 patients with diabetes and/or hypertension hospitalized from July 2010 to February 2011. The patients were divided into narrow group (ABI < 0.9), normal group (0.9≤ABI < 1.3), and calcification group (ABI≥1.3) according to the value of ABI, and also into narrow group (TBI < 0.7) and normal group (TBI≥0.7) according to the value of TBI. The correlation of ABI with TBI was analyzed, and the differences in age, obesity parameters, biochemical indicators and other factors were compared between the groups. Influence of high-sensitivity C-reactive protein (hs-CRP) on ABI and TBI was further analyzed. Results Only when ABI < 0.9, ABI and TBI have significant correlation (r=0.826, P < 0.01). W hen the group comparison based on ABI values, it was shown that the age and hs-CRP were significantly higher in the narrow group than in the normal group and calcification group (P < 0.01). The comparison between groups based on TBI values indicated that the age, systolic blood pressure and hs-CRP in the narrow group were significantly higher than those in the normal group (P < 0.01 or P < 0.05). ABI and TBI in the normal hs-CRP group were significantly higher than those in high hs-CRP group (P < 0.05). Conclusion Hs-CRP may play an important role in the development and progression in peripheral arterial atherosclerosis. Therefore, ABI and TBI measurements in combination with hs-CRP level can improve early diagnosis of arterial disease of lower extremity.

Objective To explore the influence of intra-abdominal fat (IAF) accumulation on ambulatory blood pressure (ABP). Methods Four hundred and forty-eight hospitalized patients with cardiovascular and metabolic diseases, including 235 males and 213 females, aged 20-85 (55±12) years old, were enrolled in this study. The abdominal fatty thickness was measured with B-mode ultrasound. Simultaneously the patient received 24hABP monitoring. The patients were divided into excessive IAF group, normal group, and quintile subgroups according to the cut-off points (male 38.5mm, female 34.7mm) for observing the difference in indexes of ambulatory blood pressure between different groups/subgroups. Results The 24h mean systolic BP (24hMSBP), 24h mean BP (24hMBP), 24h mean diastolic BP (24hMDBP), daytime MSBP (dMSBP), daytime MBP (dMBP), daytime MDBP (dMDBP), nighttime MSBP (nMSBP), nighttime MBP (nMBP), night MDBP (nMDBP) were significantly higher in the excessive IAF group than in the normal group (P < 0.05). However, the elevation of ABP was not a simple gradual linear elevation corresponding to a gradual increase in IAF thickness, but manifested an approximately U-shaped trend. Pearson correlation analysis showed IAF thickness was positively correlated with all the indexes of 24hABP, while partial correlation analysis after adjustment for age and sex showed IAF thickness was positively correlated with 24hSBP, 24hMBP, dMBP and nMBP. Conclusion The relationship between IAF thickness and ABP presents a U-shaped curve, which may provide an enlightenment in controlling blood pressure by weight loss in clinical work.

Objective To explore the relationship between intra-abdominal fat accumulation and heart rate variability. Methods A total of 353 patients with hypertension were enrolled in this study, among them there were 197 males and 156 females, aged from 27 to 85 years old with a mean of 55±13 years. All the patients received abdominal fat ultrasonography, 24-hour ambulatory ECG and blood biochemical tests, and they were divided into intra-abdominal fat accumulation group and normal intra-abdominal fat group according to the fat thickness measured by B-mode ultrasound value (male ≥38.5mm, female ≥34.7mm). They were redivided into four subgroups based on interquartile range of the fat thickness for comparing the difference in heart rate variability between 4 groups. Results Each subject had a 24-hour ECG recording taken and the standard HRV time-domain indices: SDNN (standard deviation of the normal-to-normal RR intervals), reflecting total nervous tension, SDANN (standard deviation of the averages of RR intervals in all 5-minute segments), reflecting sympathetic tone, and RMSSD (the root mean square successive differences) and SDNN index (mean of the standard deviations of RR intervals in all 5-minute segments), reflecting vagal nerve tone were determined. Results showed all the aforesaid indices were lower in the intra-abdominal fat group than in the normal intra-abdominal fat group (P < 0.05). Hierarchical analysis by interquartile revealed that PNN50 (the percentage of successive RR intervals that differed by more than 50ms), SDNN, SDANN, RMSSD and SDNN index were significantly lower in abdominal fat thickness > 38.0mm group than in < 15.5mm group (P < 0.05); PNN50, SDNNN, SDANN and RMSSD were significantly lower in the > 38.0mm group than in 15.6-27.0mm group; SDNN and SDNN index were significantly lower in the 27.1-38.0mm group than in < 15.5mm group; SDNN was significantly lower in the 27.1-38.0mm group than in 15.6-27.0mm group. Linear regression analysis indicated intra-abdominal fat thickness, fasting blood glucose and sex were the main risk factors of the SDNN; abdominal fat thickness and sex were main factors influencing SDANN, and abdominal fat thickness, fasting blood glucose and diastolic blood pressure were main influencial factors of SDNN index. Conclusion Intra-abdominal fat accumulation may significantly reduce the heart rate variability in hypertension patients.

Technical innovation is the power and resource for the sustainable and healthy development of enterprises, and is re- lated to the improvement of social productivity and the establishment and improvement of national innovation system. Technical innovation is the process of the enterprise using the original knowledge and transforming it into new tech- nology. The input and output of knowledge of (i.e., creating new technology) presents S curve, experiencing the stage of imitating type, fusion type and original type, which is subjected to the synergistic action of institutional arrangements factor and its operating factors. Through the analysis of evolution mechanism of different stages of technological inno- vation stages, this paper verifies the rationality and scientific nature of the theoretical assumptions.

The waveform controlled short-circuit CO2 arc welding has been developed and applied in industries widely. To guarantee its process stability and weld quality in automatic applications further, the torch-height, the distance from torch to workpiece, which may be altered by the welding distortion and assembling errors of joints, is detected via measuring the wire electrode extension during the metaphase of short-circuit and then controlled. The acquired data is filtered by rule-based fuzzy algorithm and/or shift-average method. The experimental results, validated by slope and lap-joint welding, show that the detection and control system has excellent stability and dynamic response under different welding conditions, such as slope angle, wire feeding rate and welding speed, this will make the welding process more stability and the weld quality improved.

Background We recently showed that increased expression of the transient receptor potential canonical Type 3 (TRPC3) channel is associated with genetic hypertension. It is unknown whether store-operated TRPC3 channels, which are activated after depletion of intracellular stores, or second messenger-operated TRPC3 channels, which are activated by 1-oleoyl-2-acetyl-sn-glycerol, show augmented responses in monocytes in genetic hypertension and support the development of vascular disease. Methods Using the fluorescent-dye technique, we studied store-depleted and thapsigargin-induced, store-operated calcium influx and 1-oleoyl-2-acetyl-sn-glycerol-induced second messenger-operated calcium influx into monocytes from spontaneously hypertensive rats (SHRs) and from normotensive Wistar-Kyoto rats (WKYs). The RNA interference for the downregulation of TRPC3 in monocytes by small, interfering RNA (siRNA) was performed and evaluated using in-cell Western assay. Results Thapsigargin-induced, store-operated calcium influx was significantly elevated in SHRs and was approximately double that observed in WKYs. In the presence of nimodipine, the thapsigargin-induced, store-operated calcium influx was also significantly higher in SHRs compared with WKYs. After stimulation of monocytes by angiotensin II, calcium influx was significantly elevated in SHRs, and was approximately double that observed in WKYs. The 1-oleoyl-2-acetyl-sn-glycerol-induced, second messenger-operated calcium influx was also significantly elevated in SHRs compared with WKYs. Thapsigargin-induced, store-operated calcium influx was reduced by the inhibitor 2-aminoethoxydiphenyl borane. After TRPC3 knockdown, the thapsigargin-induced, store-operated calcium influx, as well as 1-oleoyl-2-acetyl-sn-glycerol-induced calcium influx, was significantly more reduced in cells from SHRs compared with WKYs. Conclusions The increased store-operated and second messenger-operated calcium influx through TRPC3 channels in monocytes from SHRs may be responsible for a more aggressive effect in promoting vascular disease in genetic hypertension.

Growing evidence has shown that apelin/APJ system functions as a critical mediator of cardiac development as well as cardiovascular function. Here, we investigated the role of apelin in the cardiomyogenic differentiation of mesenchymal stem cells derived from Wharton's jelly of human umbilical cord in vitro. In this research, we used RNA interference methodology and gene transfection technique to regulate the expression of apelin in Wharton's jelly-derived mesenchymal stem cells and induced cells with a effective cardiac differentiation protocol including 5-azacytidine and bFGF. Four weeks after induction, induced cells assumed a stick-like morphology and myotube-like structures except apelin-silenced cells and the control group. The silencing expression of apelin in Wharton's jelly-derived mesenchymal stem cells decreased the expression of several critical cardiac progenitor transcription factors (Mesp1, Mef2c, NKX2.5) and cardiac phenotypes (cardiac α-actin, β-MHC, cTnT, and connexin-43). Meanwhile, endogenous compensation of apelin contributed to differentiating into cells with characteristics of cardiomyocytes in vitro. Further experiment showed that exogenous apelin peptide rescued the cardiomyogenic differentiation of apelin-silenced mesenchymal stem cells in the early stage (1-4 days) of induction. Remarkably, our experiment indicated that apelin up-regulated cardiac specific genes in Wharton's jelly-derived mesenchymal stem cells via activating extracellular signal-regulated kinase (ERK) 1/2 and 5.

Recent studies have indicated that stem cell implantation increases cardiac function by repairing damaged myocardium. We investigated whether intracoronary transplantation of autologous bone marrow-derived mononuclear cells (BMMCs) confers beneficial effects in patients with refractory chronic heart failure. Twenty-eight patients received standard heart failure medication and BMMC transplantation (BMMC treatment) or standard medication only (controls). BMMCs were harvested from each patient. Clinical manifestations, biochemical assays, rhythm studies, echocardiograms, and positron emission tomograms were recorded. Fourteen patients with cell grafting had symptomatic relief of heart failure within 3 days. Left ventricular ejection fraction increased by 9.2% and 10.5% at 1 week and 3 months after the procedure, respectively, versus baseline (p0.01 for the 2 comparisons). Left ventricular end-systolic volume decreased by 30.7% after 3 months (p0.01). Brain natriuretic peptide levels at days 3 and 7 after cell infusion significantly decreased by 69.2% and 70.4%, respectively, whereas atrial natriuretic peptide levels increased by 30.1% at day 7. Positron emission tomographic analysis showed a significant increase in cell viability of 10.3% in the infarcted zone. No patient died in the BMMC-treated group at 6-month follow-up. In contrast, heart failure did not improve in any control patient. Left ventricular ejection fraction decreased by 7.2% after 3 months. Two control patients died from heart failure within 6 months. In conclusion, this is the first demonstration in humans that intracoronary BMMC transplantation is a feasible and safe therapeutic strategy to decrease symptoms, increase cardiac function, and possibly prolong life in patients with end-stage heart failure refractory to standard medical therapy.

Background and Purpose— It is still controversial whether elevated plasma homocysteine and the C677T polymorphism of methylenetetrahydrofolate reductase (MTHFR) gene are risk factors for stroke. The aim of the present study was to investigate the association between the 2 factors and stroke in Chinese in a large case-control study. Methods— We recruited 1823 stroke patients (807 cerebral thrombosis, 513 lacunar infarction, 503 intracerebral hemorrhage) and 1832 controls. Total plasma homocysteine was determined by high-performance liquid chromatography. C677T polymorphism was genotyped by polymerase chain reaction and Hin fI digestion. Results— Total plasma homocysteine levels were significantly higher in cases than controls (median, 14.7 versus 12.8 μmol/L; P P P P =0.017). The TT genotype was associated with an increased risk for overall stroke (odds ratio, 1.27; 95% CI, 1.04 to 1.56) and thrombotic stroke (odds ratio, 1.37; 95% CI, 1.06 to 1.78). Conclusions— The C677T polymorphism of the MTHFR gene was associated with increased risk of cerebral thrombotic stroke in Chinese. Total plasma homocysteine was correlated with both ischemic and hemorrhagic stroke, suggesting potential initiation of homocysteine-lowering therapy in this population.

Background and Purpose— It is still inconclusive whether high plasma lipoprotein(a) [Lp(a)] level is a risk factor for stroke. Small sample size and different ethnic groups and methodologies might be contributors to the conflicts in study results. The purpose of the present study was to investigate the association between plasma Lp(a) levels, pentanucleotide TTTTA repeat (PNTR) polymorphism of the apolipoprotein(a) [apo(a)] gene, and Chinese stroke in a case-control study. Methods— We recruited 1825 cases with stroke (44.3% cerebral atherothrombosis, 28.3% lacunar infarction, and 27.3% intracerebral hemorrhage) and 1817 controls from 7 centers in China. Lp(a) concentrations were quantified by enzyme-linked immunosorbent assay. The PNTR polymorphism of the apo(a) gene was determined by polymerase chain reaction–polyacrylamide gel electrophoresis. Conditional multivariate logistic regression analysis was used to identify independent risk factors for stroke and its subtypes. Results— Lp(a) levels were significantly higher in cases than in controls (median, 28.5 versus 23.1 mg/dL; P Conclusions— Our results indicate for the first time that low numbers of apo(a) PNTR and plasma Lp(a) levels are independently associated with both ischemic and hemorrhagic stroke in Chinese.

Different from the traditional researches only focus on the relationship between the real exchange rate and trade balance, terms of trade, gross domestic product. This paper led the relevance between real exchange rate and trade structure Balassa-Samuelson effect. From the perspective of the total manufactured goods trade structure, an empirical study was done with annual data 1981–2012 by co-integration technique. The results showed that China’s total trade structure had the co-integration relationship with the real exchange rate, and it had a more obvious effect on the incidence and model fitting. So four basic economic factors were chosen which were the variables of aggregate trade structure, trade conditions, openness, monetary supply, these constructed RMB equilibrium real exchange rate estimation model. It would give theoretical supports to exploration of RMB real exchange rate.

To explore the correlation between computed tomographic (CT) vascular convergence sign and enhancement value in patients with pulmonary nodules.A total of 708 consecutive patients with pulmonary nodule received dual-source CT scan from January 2010 to January 2012. They were divided into vascular convergence sign group (including 4 subgroups) and non-vascular convergence sign group. Then the correlation between CT vascular convergence sign and enhancement values was analyzed.The enhancement values in vascular convergence sign group were significantly higher than those in non-vascular convergence sign group ((27.6 ± 10.5) vs (3.2 ± 2.8) HU, P = 0.000). The CT enhancement values in lesions tended to increase with the number of connecting blood vessels. However, no significant differences existed among the subgroups (P0.05). The accuracy of vascular convergence sign for detection of pulmonary malignant nodules was 84.9%, 70.6% and 60.3% according to the standards of CT enhancement values ≥ 15, 20, 25 HU respectively. The sensibility, specificity and accuracy of determining pulmonary malignant nodules were 97.2%, 68.8% and 93.7% according to the standard of vascular convergence sign. The accuracy of determining pulmonary nodules' CT enhancement values ≥ 15 HU was 88.1% according to the standard of vascular convergence sign.Vascular convergence sign may be used to indicate the enhancement of pulmonary nodules when CT enhancement images are not available.

Metabolic syndrome has received great attention because it poses a potential cardiovascular hazard, which increases the risk of lower extremity atherosclerosis. However, the relationship between the components of metabolic syndrome and the onset of chronic venous disorder of the lower extremities remains unexplained.This study investigated the characteristics of cardiometabolic risk factors of early chronic venous disorder of the lower extremities in subjects with cardiometabolic risk. The characteristics of risk factors and diabetes-related complications in diabetic patients with early chronic venous disorder of the lower extremities were also investigated. In addition, the association between early chronic venous disorder and atherosclerosis of the lower extremities was analysed. The study examined 782 subjects with cardiometabolic risk factors, including obesity, hypertension, diabetes mellitus and dyslipidaemia. Lower extremity venous function was measured by digital photoplethysmography.Women had a higher prevalence of early chronic venous disorder than did men (p 0.01). Male subjects with early chronic venous disorder had a higher systolic blood pressure than those with normal venous function (p 0.01), and female subjects with early chronic venous disorder had a higher fasting plasma glucose level than did controls (p 0.05). The prevalence of diabetes mellitus is also significantly higher in female patients with early chronic venous disorder (p = 0.000). Diabetic patients with early chronic venous disorder not only had higher fasting plasma glucose and total cholesterol levels but also had more serious macrovascular complications than the control group. The independent risk factors of early chronic venous disorder in female subjects with cardiometabolic risks were age and fasting plasma glucose in men it was only age Women face a two times greater risk than men. The independent risk factors of early chronic venous disorder in diabetic patients were age, gender, HbA1c and triglyceride levels Women had an almost 12 times greater risk of early chronic venous disorder than men. Among the diabetic patients, the prevalence of early chronic venous disorder did not differ by ankle-brachial index.Female subjects with cardiometabolic risk factors or female diabetic patients face a greater risk of early chronic venous disorder than do male subjects. Diabetic patients with early chronic venous disorder had more serious macrovascular complications than did the controls, and the early venous function was found to be correlated with the blood glucose level and triglyceride status.

To investigate glucose metabolism status and its relationship with blood pressure, obesity, renal function and cardio-cerebral vascular events in Chinese essential hypertensive patients.Essential hypertensive patients without diabetic history were enrolled in this cross-sectional survey. All patients filled in questionnaires and received physical examination and laboratory tests. Oral glucose tolerance test (OGTT, fasting and 2 hours glucose level after drinking the 75 g glucose solution) was performed in patients who signed the informed consent.(1) The control rate of systolic BP was lower in patients with dysglycemia than in patients without dysglycemia (41.0% vs. 46.4%, P = 0.000). (2) The albuminuria detection rate and the abnormal rate of estimated glumerular filtration rate (eGFR) increased significantly with the deterioration of glucose metabolism. (3) Multifactor-analysis showed that abnormal waist circumference, decreased eGFR and presence of albuminuria were independent risk factors for abnormal glucose metabolism. Cardiovascular events was significantly higher in patients with abnormal glucose metabolism than patients with normal glucose metabolism.Abnormal glucose metabolism is common in Chinese essential hypertensive patients. When complicated with abnormal glucose metabolism, essential hypertensive patients had poor blood pressure control rate and were related to higher cardiovascular risk.

To explore the characteristics and related risk factors of arterial elasticity in persons with prehypertension, high-normal blood lipid and(or) impaired glucose regulation(impaired fasting glucose and(or) impaired glucose tolerance).After receiving physical and biochemical examinations, a total of 1238 persons were enrolled. Among them, the etiologies were prehypertension (n = 65), high-normal blood lipid (n = 156), impaired glucose regulation (n = 159), prehypertension and high-normal blood lipid (n = 85), prehypertension and impaired glucose regulation (n = 77), high-normal blood lipid and impaired glucose regulation (n = 55) and prehypertension, high-normal blood lipid and impaired glucose regulation (n = 9). Also 332 healthy subjects, 113 hypertensive patients, 150 hyperlipidemics and 37 diabetics were enrolled as controls. Systemic vascular compliance (SVC), systemic vascular resistance (SVR), brachial artery distensibility (BAD) were measured with Dynapulse 200 M (Pulse Metric, Inc., USA).In persons with prehypertension, SVC was lower than healty group ((1.14 ± 0.20) ml vs (1.26 ± 0.23) ml, P0.01)and higher than hypertensive group ((1.11 ± 0.18) ml, P = 0.011), SVR higher than healty group (157 ± 29) kPa×s×L(-1) vs (148 ± 25) kPa×s×L(-1), P = 0.012) and lower than hypertensive group ((166 ± 36) kPa×s×L(-1), P0.01)and BAD lower than healty group(5.93% ± 1.14% vs 6.50% ± 1.30%, P0.01). Among different groups with prehypertension, high-normal blood lipid and(or) impaired glucose regulation, SVC, SVR and BAD had significant differences. As indicated by multiple linear regression analysis, blood pressure was an independent risk factor of arterial elasticity.Vascular function becomes damaged in prehypertensive stage. As an independent risk factor, blood pressure had more potent effect than lipid and blood glucose. Multiple cardiovascular risk factors with high-normal value may affect vascular function more strongly.

At present, there are still significant barriers that impede the clinical use of hESCs and iPS cells, including ethics, immunorejection, tumorigenesis from hESCs, and teratoma formation from iPS cells. It is therefore necessary to search for alternative sources of stem cells. WJ-MSCs originate from embryonic epiblasts and possess properties intermediate between hESCs and adult stem cells. However, the stemness properties of molecules in WJ-MSCs remain unclear compared to those of hESCs. In the present study, we isolated WJ-MSCs by a nonenzymatic method. Further, using microarray analysis by Affymetrix GeneChip and functional network analyses, we determined the degree of expression of stemness genes exhibited by the Human Stem Cell Pluripotency array. We also defined a wide range of stem cell gene expression in the WJ-MSCs in comparison with hESCs. At the same time, the definitive markers of early cardiac precursor cells and more committed progenitors were further characterized in WJ-MSCs. Our results demonstrated for the first time that WJ-MSCs had significant expression of undifferentiated human embryonic stem cell core markers, such as SOX2, NANOG, LIN28, SSEA1, SSEA3, SSEA4, KLF4, c-MYC, CRIPTO, and REX1, with a relatively lower level of expression than in hESCs. We also found WJ-MSCs have high expression of early cardiac transcription factors, such as Flk-1, Isl-1, and Nkx2.5. Functional analysis revealed signature genes of WJ-MSCs with specific roles involved in immune, cytoskeletal, and chemokine regulation, cell adhesion, and cell signaling. Our study indicated that there is a significant overlap between the stemness genes expressed by hESCs and WJ-MSCs. WJ-MSCs harbor a true stem cell population and are promising cells for stem cell-based therapies.

To investigate the role of dietary capsaicin in activating transient receptor potential vanilloid 1 (TRPV1) and thus influencing the vascular dysfunction mediated by high-fat diet and the potential mechanisms.A total of 80 male C57BL/6J mice aged 10 weeks were equally divided into four groups, in which the mice were fed with normal diet (ND), normal diet plus capsaicin (NC), high-fat diet (HD), or high-fat diet plus capsaicin (HC) for 20 weeks. Tail-cuff blood pressure (BP), vascular function of mice aortic rings, expressions of voltage-gated potassium-channel Kv1.4, RhoA and Rho kinase in aorta were examined.Compared with ND group, both nitroglycerin [(18.9 +/- 13)% vs. 100%, P0.01] and acetylcholine [(26 +/- 12)% vs. 100%, P0.01] induced vasorelaxation of aortic rings were significantly reduced in HD group. Both endothelium dependent and independent aortic rings vasorelaxation in HC group were significantly improved compared with that in HD group [acetylcholine: (69 +/- 15)%; nitroglycerin: (46.5 +/- 6)%, P0.05], but still reduced compared with that in ND group (P0.05, P0.01). High fat diet induced the expression of RhoA and Rho kinase. Dietary capsaicin down-regulated the expression of RhoA and Rho kinase but up-regulated the expression of Kv1.4 in aorta in mice fed with normal or high fat diet (all P0.05).Dietary capsaicin can ameliorate vasorelaxation dysfunction mediated by high-fat diet. The potential mechanisms may be related with TRPV1 activation, which in turn stimulates potassium channel and inhibits RhoA and Rho kinase in the vasculature.

Objective: Tissue kallikrein (TK) cleaves kininogen to produce the potent bioactive compounds kinin and bradykinin, which lower blood pressure and protect the heart, kidneys, and blood vessels. Reduction in TK levels is associated with cardiovascular disease and diabetes in animal models. In this study, we investigated the association of TK levels with event-free survival over 5 years in Chinese first-ever stroke patients. Methods: We conducted a case–control study with 1,268 stroke patients (941 cerebral infarction, 327 cerebral hemorrhage) and 1,210 controls. Plasma TK levels were measured with an enzyme-linked immunosorbent assay. We used logistic regression and Cox proportional hazards models to assess the relationship between TK levels and risk of first-time or recurrent stroke. Results: Plasma TK levels were significantly lower in stroke patients (0.163 ± 0.064mg/l vs 0.252 ± 0.093mg/l, p < 0.001), especially those with ischemic stroke. After adjustment for traditional risk factors, plasma TK levels were negatively associated with the risk of first-ever stroke (odds ratio [OR], 0.344; 95% confidence interval [CI], 0.30–0.389; p < 0.001) and stroke recurrence and positively associated with event-free survival during 5 years of follow-up (relative risk, 0.82; 95% CI, 0.74–0.90; p < 0.001). Compared with the first quartile of plasma TK levels, the ORs for first-ever stroke patients were as follows: second quartile, 0.77 (95% CI, 0.56–1.07); third quartile, 0.23 (95% CI, 0.17–0.32); fourth quartile, 0.04 (95% CI, 0.03–0.06). Interpretation: Lower plasma TK levels are independently associated with first-ever stroke and are an independent predictor of recurrence after an initial stroke. ANN NEUROL 2011

To explore the relationship between proliferation and hypertrophy of vascular smooth muscle cells and PDGF-AA and PDGFR-alpha expression in SHRs and the role of [Ca2+]i in it.Express difference of PDGF-AA, PDGFR-alpha, PDGFR-beta in SHR/WKY-VSMC was observed by Western blot. The effect of Ca2+ inhibitor (nimodipine) on proliferation, hypertrophy and free Ca2+ concentration of SHR-VSMC induced by PDGF-AA was observed by Western blot, [3H] incorporation and fluorescent digital image technique.PDGF-AA and PDGFR-alpha expression was markedly increased in SHR-VSMC than in WKY-VSMC, but PDGFR-beta was not different in SHR and WKY-VSMC. PDGF-AA-stimulated PCNA expression, [3H] incorporation and [Ca2+]i increasing were observed in SHR-VSMC. Dose-dependent nimodipine-inhibited PCNA expression, [3H] incorporation and [Ca2+]i increasing induced by PDGF-AA also were observed in SHR-VSMC.Spontaneously expression increasing of PDGF-AA and PDGFR-alpha in spontaneously hypertension rats (SHRs) may be one of the important factors on vascular reactivity and vascular modeling mediated through proliferation and hypertrophy in SHR-VSMC, and [Ca2+]i play an important role in this process.

To assess whether variants in the vascular endothelial growth actor receptor 2 (VEGFR-2) gene confer susceptibility to stroke risk.Association between gene variant rs2305948 (Val297Ile) and the risk of stroke was investigated in a multi-center case-control study, which comprised of 1849 patients with stroke (812 cerebral atherothrombosis, 530 lacunar infarction, and 507 intracerebral hemorrhage) and 1798 controls, and then replicated in the second independent stroke study (327 cases and 327 controls). The effect of Val297Ile on the binding ability of VEGFR-2 to VEGF was determined by a radioligand binding assay.The frequencies of carriers with variant 297Ile were significantly higher in patients with hemorrhagic stroke than in controls [297Val/Ile: 155(30.6%) versus 351 (19.5%), 297Ile/Ile: 18 (3.2%) versus 16 (1.0%); P0.01]. The variant 297Ile was significantly associated with increased risk of hemorrhagic stroke (odds ratio 2.25, 95% confidence interval 1.70-2.96; P0.01), and replication in the second stroke study obtained similar results. The substitution of Val to Ile at the amino acid residue 297 led to an increased equilibrium dissolved constant between VEGF and its receptor VEGFR-2 [297Val (87 +/- 9) pmol/L versus 297Ile (195 +/- 36) pmol/L, P0.01].The VEGFR-2 gene variants may serve as novel genetic markers for the risk of hemorrhagic stroke.

We previously reported that intracoronary implantation of bone marrow mononuclear cells (BMMC) into ischemic hearts improved cardiac function after myocardial infarction. However, the mechanisms have not been elucidated. The present study investigates whether apelin, a newly described inotropic peptide with important cardiovascular regulatory properties, contributes to the functional improvement in patients with severe heart failure after cell transplantation. Forty consecutive patients with severe heart failure secondary to myocardial infarction were assigned to the BMMC therapy group or the standard medication group according to each patient's decision on a signed consent document. In 20 patients intracoronary cell infusion was performed, and another 20 patients were matched to receive standard medication as therapeutic controls. An additional 20 healthy subjects were designated as normal controls. Clinical manifestations, echocardiograms, and biochemical assays were recorded. Plasma apelin and brain natriuretic protein (BNP) levels were determined by enzyme immunoassay. Baseline levels of plasma apelin were significantly lower in all heart failure patients compared to normal subjects. In patients who underwent cell transplantation, apelin increased significantly from 3 to 21 days after operation, followed by significant improvement in cardiac function. In parallel, BNP varied inversely with the increase of apelin. In patients receiving standard medical treatment, apelin remained at a lower level. Our findings indicated that increased apelin levels following cell therapy may act as a paracrine mediator produced from BMMCs and play an important role in the treatment of heart failure through autocrine and paracrine mechanisms.

Plasma homocysteine concentrations have been associated with the risk of stroke, but its relevance to secondary vascular events and mortality after stroke remains unclear because of inconsistent results from clinical trials. The aim of the present study was to investigate whether plasma homocysteine levels and the MTHFR (methylenetetrahydrofolate reductase) variant C677T contributed to the risk of stroke recurrence and all-cause mortality in a large prospective cohort of stroke patients in a Chinese population. A total of 1823 stroke patients (age, 35–74 years) were recruited during 2000–2001 and prospectively followed-up for a median of 4.5 years. During the follow-up, 347 recurrent strokes and 323 deaths from all-causes were documented. After adjustment for age, gender and other cardiovascular risk factors, a high homocysteine concentration was associated with an increased risk of 1.74-fold for stroke recurrence {RR (relative risk), 1.74 [95% CI (confidence interval), 1.3–2.3]; P