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Background Patients with gastric cancer often suffer from generalized and progressive reduction of skeletal muscle mass and strength, which negatively affects the quality of life (QOL). In this study, we explored the impact of sarcopenia on QOL and overall survival (OS). Methods From December 2015 to June 2017, 135 patients underwent radical gastrectomy at the First Affiliated Hospital of Wenzhou Medical University. Based on the diagnostic criteria of the Asian Working Group for Sarcopenia (AWGS), data including handgrip strength, 6-m gait speed and muscle mass were collected and analyzed. EORTC QLQ-C30 and EORTC QLQ-STO22 were used to evaluate the QOL before surgery, 1, 3 and 6 months after surgery. Results A total of 27 out of the 135 patients (20.00%) were diagnosed with sarcopenia. Compared with non-sarcopenia group, patients in sarcopenia group had a higher incidence of postoperative complications (14.80% vs. 40.70%, p = 0.003), and more hospitalization costs (p = 0.029). The scores of eating restriction (p = 0.026), anxiety (p = 0.045) and body image (p = 0.046) were significantly higher in sarcopenia group at postoperative 6 months. Besides, sarcopenia was an independent risk factor for global health status at 6 months after operation (OR: 2.881, 95% CI: 1.110–7.475, p = 0.030) and OS (HR: 3.140, 95% CI: 1.255–7.855, p = 0.014). Other factors, including tumor stage III and the postoperative complications, had negative influences on OS. Conclusion Sarcopenia is a predictive factor of poor QOL and prognosis in patients with gastric cancer.

Water-air interactions caused by water level changes over a karst cavity can lead to sinkhole collapse. Declining water levels in a two-layered cover (clayey upper layer and sandy lower layer) above a karst cavity will lead to changes in the air pressure inside both the cover layers and the cavity. The change in air pressure can cause changes in the rate of water level decline and induce subsidence and collapse. In this study, a mathematical formula was derived and used to better understand the water-air interaction mechanism. Air velocity, vacuum variation in the cover, cumulative air intake, and elapsed time in the water level decline process are considered. A physical model was used to conduct laboratory simulations of the water-air interaction process and to determine the relationship between collapse and the water-air interaction. The main findings of this work are as follows: (1) Water level declines cause changes in air pressure both inside the cover and the cavity, and, conversely, the velocity of the water level decline was influenced by the variable air pressure; water-air interaction is obviously occurring. (2) With a low permeability cover layer, the declining water level mainly generates vacuum suction, but also erosion of the underlying high permeability sandy layer; vacuum suction and erosion can lead to subsidence or collapse of the cover. (3) Physical model simulations are useful for representing the phenomena of water-air interactions in karst cavities, and provide a practical way to understand the mechanism of collapse in karst terrain.

Uncorrected obesity facilitates premature aging and cardiovascular anomalies. This study examined the interaction between obesity and aging on cardiac remodeling and contractile function.Cardiac echocardiographic geometry, function, morphology, intracellular CaOur results displayed reduced survival in ob/ob mice. Obesity but less likely older age dampened echocardiographic, geometric, cardiomyocyte function and intracellular CaOur data suggest disparate age-associated obesity response in cardiac remodeling and contractile dysfunction due to phosphorylation of Akt, eNOS and stress signaling-related oxidative stress.

This study presents assessments of the spatial variability of a soil landslide in the Three Gorges Reservoir Area in China. The results challenge the idea that variability of permeability within a landslide is secondary. Consequently, it cannot be assessed through single representative values. It was found that its variability spans two orders of magnitude, a consequence of it being influenced by both morphology and regolith properties. Identification of zones that display comparable behavior can be done through assessment of remote-sensing images collected by drones, as growth patterns of vegetation correspond well with zones that displayed similar permeability coefficients within the landslide body. Furthermore, extensive variability of permeability was caused by a diverse range of seepage mechanisms, namely pipe network flow, interface network seepage and pore water seepage. Thus, the hydraulic behavior of large landslide bodies is remarkably complex.

To investigate the applicability of astragaloside IV (AG) for the treatment of refractory neuropathic pain, we systemically evaluated the antinociceptive activity of AG in the animal model of chronic constriction injury. We studied behaviors, electrophysiology, and biochemistry from day 2 to day 23 after the surgery. We found that when administered intraperitoneally at the dose of 60 mg/kg, AG caused significant inhibition of allodynia and hyperalgesia induced by mechanic and thermal stimuli as well as downregulation of the expressions of a series of proteins involved in mediating neuropathic pain in the dorsal root ganglia, such as P2X purinoceptor 3, glial cell-derived neurotrophic factor, glial cell-derived neurotrophic factor family receptor α1, and transient receptor potential cation channel subtypes A1 and V1. Further investigation showed that AG restored the nerve conduction velocity and the histological structure of the damaged sciatic nerve on day 23 after the surgery. Moreover, results from immunoelectron microscope showed that glial cell-derived neurotrophic factor family receptor α1 induced by AG could form a circular band in the myelin debris between the injured axons and Schwann cells, contributing toward restoration of the damaged nerve. In conclusion, in our animal model, AG effectively inhibited the neuropathic pain induced by chronic constriction injury.

Stroke is a major cause of disability and death worldwide. Prevention aimed at risk factors of stroke is the most effective strategy to curb the stroke pandemic. Hypertension is one of the most important risk factors for stroke. Despite the substantial evidence of the benefits of lowering blood pressure, conventional treatment does not normalize the burden of major cardiovascular events in patients with hypertension. Fully understanding the factors involved in the hypertension-induced stroke helps to develop new strategies for stroke prevention. Antihypertensive therapies selected should have positive blood pressure-independent effects on stroke risk. This review summarizes the factors involved in the hypertension-induced stroke, such as oxidative stress, inflammation, and arterial baroreflex dysfunction, and potential strategies for its prevention, therefore, provides clues for clinicians.

Effect of Ce on the strength and ductility of 1Cr18Mn8Ni5N stainless steel has been studied. The results show that the strength and ductility of 1Cr18Mn8Ni5N stainless steel are markedly improved when appropriate content of Ce is added in the steel. The 1Cr18Mn8Ni5N stainless steel with 0.016 wt.% Ce presents the best-optimized mechanical properties.

Six methods to determine axial pile capacity directly based on piezocone penetration test (CPTU) data are presented and evaluated. Analyses and evaluation were conducted on three types piles that were failed during pile load testing. The CPT methods, as well as the CPTU methods, were used to estimate the load carrying capacities of the investigated piles (Qp ). Pile load test were used to determine the measured load carrying capacities (Qm). The pile capacities determined using the different methods were compared with the measured pile capacities obtained from the pile load tests. Two criteria were selected as bases of evaluation: the best fit line for Qp versus Qm and the arithmetic mean and standard deviation for the ratio Qp /Qm. Results of the analyses showed that the best methods for determining pile capacity are the CPTU methods.

The use of the piezocone penetration test (CPTU) in a geotechnical site investigation offers direct field measurement on stratigraphy and soil behavior. Compared with some traditional investigation methods, such as drilling, sampling and field inspecting method or laboratory test procedures, CPTU can greatly accelerate the field work and hereby reduce corresponding operation cost. The undrained shear strength is a key parameter in estimation of the stability of natural slopes and deformation of embankments in soft clays. This paper provides the measurements of in situ CPTU, field vane testing and laboratory undrained triaxial testing of Lianyungang marine clay in Jiangsu province of China. Based on the literature review of previous interpretation methods, this paper presents a comparison of field vane testing measurements to CPTU interpretation results. The undrained shear strength values from both the field vane tests and cone penetration resistances are lowest at the mid-depths of the marine clay layers...

Vagus nerve stimulation inhibits proinflammatory cytokine production by signaling through the alpha7 nicotinic acetylcholine receptor (alpha7nAChR). Anisodamine, a muscarinic acetylcholine receptor antagonist, has been used clinically in China for treatment of various shocks, but the mechanism was poorly understood. Here, we tested the hypothesis whether anisodamine attained its antishock effect through activation of alpha7nAChR.: Randomized and controlled in vitro and in vivo study.Research laboratory and animal facility rooms.Sprague-Dawley rats, Kunming mice, alpha7nAChR-deficient mice, and RAW264.7 cells.Sprague-Dawley rats were injected with lipopolysaccharide (LPS) (15 mg/kg, intravenous) to induce septic shock. Methyllycaconitine, a selective alpha7nAChR antagonist, was administered (10 mg/kg, intraperitoneal) 10 minutes before anisodamine (10 mg/kg, intravenous). Mean arterial pressure was monitored and cytokines were analyzed 2 hours after the onset of LPS. In vagotomized mice and alpha7nAChR-deficient mice, the antishock effect of anisodamine was appraised, respectively. RAW264.7 cells were stained by fluorescein isothiocyanate- labeled-alpha-bungarotoxin and the fluorescence intensity was observed. Mice peritoneal macrophages were pretreated and stimulated with LPS, and tumor necrosis factor (TNF)-alpha in the supernatant was measured by enzyme-linked immunosorbent assay.Methyllycaconitine significantly antagonized the beneficial effect of anisodamine on mean arterial pressure and TNF-alpha, interleukin-1beta expression in response to LPS. The antishock effects of anisodamine were markedly attenuated in vagotomized mice and alpha7nAChR-deficient mice. In vitro, anisodamine significantly augmented the effect of acetylcholine on fluorescence intensity stained with fluorescein isothiocyanate-labeled-alpha-bungarotoxin and TNF-alpha production stimulated with LPS.These findings demonstrate that the antishock effect of anisodamine is intimately linked to alpha7nAChR-dependent anti-inflammatory pathway.

The use of the piezocone test (CPTU) in geotechnical site investigation offers direct field measurement on stratigraphy and soil behavior. Compared with some traditional investigation methods such as drilling, sampling, field inspecting method, or laboratory test procedures, CPTU can greatly accelerate the field work and thereby reduce corresponding operation cost. This article reviews previous interpretation methods of obtaining undrained shear strength, overconsolidation ratio, and coefficient of consolidation of soft soils from CPTU data, and introduces a new method, which the measured pore pressure into account. Piezocone tests with Vertek-Hogentogler CPTU truck have been complemented in a widely explored area in the soft marine deposit of Lianyungang City. Geotechnical design parameters (q t , f s , and u) obtained from CPTU and dissipation tests are evaluated for the marine clay in this area through methods based on cavity expansion (CE) and critical state (CS) theory proposed by Mayne, and compared...

Patients with Parkinson’s disease (PD) often have attenuated baroreflex function, which may occur before the onset of PD-associated movement disorders. The aim of the present study was to test whether impaired arterial baroreflex (ABR) function could contribute to the pathogenesis of PD. 6-Hydroxydopamine (8 μg in 4 μl) was microinjected into the left substantia nigra of rats to establish unilateral PD models, and bilateral PD models were established in rats by administration of rotenone by osmotic minipump for four weeks, at a dose of 2.5 mg ⋅ kg−1 ⋅ day−1. An ABR dysfunction model was obtained by performing sinoaortic denervation (SAD). Hemodynamic variables were determined in conscious rats. PD-like symptoms and dopamine content in corpus striatum (CS) were also assessed. 6-Hydroxydopamine and rotenone treatment and SAD were associated with enhanced blood pressure variability (BPV) and blunted baroreflex sensitivity (BRS). Rotenone, but not SAD, significantly reduced dopamine content in the CS, induced catalepsy, and inhibited rearing and exploratory behavior. SAD before the administration of rotenone did not aggravate the rotenone-induced dopaminergic lesion. Our findings do not support the presumption that ABR dysfunction contributes to the pathogenesis of PD in rats. Keywords:: arterial baroreflex, Parkinson’s disease, baroreflex sensitivity, blood pressure variability, sinoaortic denervation

1. The PC12 cell line, which was cloned from a rat adrenal phaeochromocytoma, is a useful model system. It expresses neuronal properties after treatment with nerve growth factor (NGF). The nervous system-specific P2X receptor subtype P2X(2) was initially cloned from PC12 cells, but little is known about the expression of other subtypes of P2X receptors in PC12 cells. The aim of the present study was to investigate whether PC12 cells express the other P2X receptors when exposed to NGF. 2. Reverse transcription-polymerase chain reaction at the mRNA level and immunocytochemisty at the protein level showed that, among the seven P2X purinoceptor subtypes, only P2X(2) was found to be expressed in undifferentiated PC12 phaeochromocytoma cells, but all seven P2X purinoceptor subtypes were expressed in differentiated PC12 cells treated with 50 microg/mL NGF. 3. Electrophysiological recordings indicated that ATP (30 micromol/L) but not alpha,beta-methylene ATP (alpha,beta-meATP; 30 micromol/L) evoked an inward current in undifferentiated PC12 cells, but both alpha,beta-meATP and ATP evoked inward currents in differentiated PC12 cells. The results indicate that the NGF-induced P2X receptors expressed in PC12 cells are functional channels. 4. The present study suggests that the NGF-induced neuronal phenotype of PC12 cells may be a model for the study of P2X heteromeric receptors.

In our previous studies, it was found that ketanserin enhanced baroreflex sensitivity (BRS) in rats and this effect was not blood pressure dependent. The present work was designed to investigate the effects of ketanserin on BRS within the nucleus tractus solitarus (NTS) and the rostral ventrolateral medulla (RVLM). In anesthetized rats, BRS were evaluated by the changes in depressor action of aortic nerve stimulation and bradycardiac response to rapid pressor action of intravenous phenylephrine. It was found that bilateral injection of ketanserin (250 pmol for each side) into the NTS not only significantly increased blood pressure, but also attenuated baroreflex function. Interestingly, when ketanserin was bilaterally injected into RVLM, a significant enhancement of BRS was found and there were no modifications in basal blood pressure and heart period. The present study demonstrates that ketanserin-induced enhancement of BRS mainly occurred within the RVLM, which might contribute to the systemic effects of ketanserin on BRS.

This study was designed to investigate the effect of end-organ damage (EOD), the initial blood pressure levels, and baroreflex sensitivity (BRS) on the blood pressure-lowering effect of nifedipine in spontaneously hypertensive rats (SHRs). Nifedipine was intravenously administered at a dose of 1 mg/kg. BP was continuously recorded in the conscious state before and after nifedipine administration. BRS was determined before drug administration. Two days after the blood pressure (BP) recording, rats were killed for organ-damage evaluation. Univariate correlation analysis showed that BP changes induced by nifedipine injection were negatively correlated with EOD score and aortic weight/length but positively correlated with left kidney weight/body weight and basal BP levels. Stepwise multiple linear regression analysis demonstrated that increase in overall end-organ damage was most significantly related to the decrease in hypotensive effect of nifedipine; increase in aortic hypertrophy was also related to a decreased fall in systolic and diastolic BP induced by nifedipine, whereas increase in initial BP levels was associated with increased hypotensive effect of nifedipine. In conclusion, the severity of overall EOD contributed more than basal BP levels to the diminished responses to nifedipine, and aortic hypertrophy was also involved in diminished drug responses.

1. The present study was designed to investigate the haemodynamic features and morphological changes in experimentally hypertensive rat models. 2. Sprague-Dawley rats were used to prepare the experimentally hypertensive models, including two-kidney, one-clip renovascular hypertensive (2K1C) rats, deoxycorticosterone acetate salt hypertensive (DOCA) rats and N(G)-nitro-l-arginine methyl ester-induced hypertensive (l-NAME) rats. Six weeks after the induction of hypertension, 24 h blood pressure was recorded and blood pressure variability (BPV) expressed by 24 h (or 12 h in the daytime and night-time study) standard deviation of the variables was calculated. Then, cardiac baroreflex sensitivity (BRS) was determined and four endogenous factors (tumour necrosis factor-alpha, interleukin-1beta, angiotensin II and endothelin-1) were measured. Finally, morphological changes were examined. 3. It was found that an increase in BPV and a decrease in BRS were accompanied by an elevation of blood pressure in all three hypertensive models. The DOCA rats had the highest BPV, whereas the l-NAME rats had the lowest BRS. 4. Morphological changes were similar in DOCA and l-NAME rats and the cardiac changes were relatively slight in 2K1C rats. Tumour necrosis factor-alpha was increased in all the three models, especially in DOCA rats. Endothelin-1 was higher in DOCA rats and angiotensin II was increased in 2K1C rats and decreased in DOCA rats. 5. In conclusion, increased BPV and decreased BRS accompanied the elevation of blood pressure in all three hypertensive models. The DOCA rats had the highest BPV and the l-NAME rats had the lowest BRS. Obvious organ damage was seen in all three hypertensive models 6 weeks after the induction of hypertension.

SUMMARY 1. Biventricular hypertrophy has been described in a high blood pressure variability (BPV) model of sinoaortic-denervated (SAD) rats without systemic hypertension. To explore the possible involvement of the lung in SAD-induced right ventricular hypertrophy (RVH), we examined lung morphology, in addition to systemic haemodynamics and ventricle morphology, in Wistar-Kyoto rats 32 weeks after SAD. 2. In Wistar-Kyoto rats 32 weeks after SAD, there existed a substantial elevation in BPV, with no change in the average level of arterial pressure. Biventricular hypertrophy following SAD was characterized by a greater hypertrophy in right than left ventricles; both absolute and normalized right ventricular weights were significantly increased by 22 and 27%, respectively, and only normalized left ventricular weight was significantly increased by 12%. No infarcts were found in any ventricles examined. 3. In the lung, the most prominent change following SAD was pulmonary vasculopathy, including wall thickening, perivascular fibrosis and cell infiltration. In pulmonary arteries with an internal diameter of 70–130 µm, the external diameter, wall thickness and wall thickness to internal diameter ratio were increased in SAD compared with control rats. 4. There was no correlation between right and left ventricular weights. In contrast with BPV-correlated left ventricular weight, right ventricular weight was correlated with the wall thickness of the pulmonary artery, but not with BPV. 5. These findings suggest that greater RVH following SAD is associated with pulmonary vasculopathy, but is not secondary to the left ventricular problems or high BPV.

Baroreflex dysfunction is associated with a higher rate of sudden death after myocardial infarction (MI). Ketanserin enhances baroreflex function in rats. The present work was designed to examine whether ketanserin improves the post-MI cardiac function and to explore the possible mechanism involved. Spontaneously hypertensive rats (SHR) were treated with ketanserin (0.3 mg·kg−1·d−1). Two weeks later, blood pressure and baroreflex function were measured, followed by a ligation of the left coronary artery. The expressions of vesicular acetylcholine transporter (VAChT) and α7 nicotinic acetylcholine receptor (α7-nAChR) in ischemic myocardium, angiogenesis, cardiac function, and left ventricular (LV) remodeling were evaluated subsequently. Ketanserin significantly improved baroreflex sensitivity (0.62±0.21 vs 0.34±0.12 ms/mmHg, P

The loss-of-function mutations of the human gene ATP13A2, which encodes a lysosomal type 5 P-type ATPase of unknown function, were found to underlie an autosomal recessive form of early-onset parkinsonism (Kufor-Rakeb Syndrome) [1]. It was reported that autophagy is involved in the pathogenesis of many chronic neurodegenerative diseases, as well as acute brain damage such as stroke [2,3]. Recently, Gusdon et al. found that ATP13A2 regulates mitochondrial bioenergetics through macroautophagy [4], which is a major response to nutrient and bioenergetic stresses, with the capacity to remove aggregated proteins and damaged organelles such as mitochondria. They proposed that decreased autophagy associated with ATP13A2 deficiency affects mitochondrial quality control, resulting in increased production of reactive oxygen species (ROS) [4]. As known, necrotic cell death as a rapid cellular response involves mitochondrial ROS production and other cellular insults, whereas autophagic cell death first attempts to clean up ROSdamaged mitochondria for survival. Stroke is the second leading cause of death in the world and the primary cause of adult disability [5]. Ischemic stroke accounts for 80% of all the cases. In ischemic stroke, neuron death occurs via necrosis and apoptosis, as well as autophagic cell death. In this study, we explored the influence of ATP13A2 knockout on the infarct size in mice with ischemic stroke, as well as the possible influence on apoptosis and autophagy involved in ischemic stroke. ATP13A2 knockout mice and corresponding wild-type mice were subjected to middle cerebral artery occlusion (MCAO) as previously described [6,7], without reperfusion. After 24 h, apoptosis/autophagy-related protein levels in infarct penumbra of cerebral cortex were detected through Western blot [8,9]. Data are expressed as mean ± SD. Differences between the two groups were evaluated by unpaired t-test. As known, formation of autophagosome requires the cooperation of microtubule-associated protein light chain 3 (LC3). LC3 is converted into LC3-I and then LC3-II, which is the marker of autophagosome. Our results showed that ATP13A2 knockout increased the level of LC3-II in infarct penumbra (by 16.1%, Figure 1A). Furthermore, the expression of pro-apoptotic protein Bax and apoptosis executer caspase-3 was increased in ATP13A2 knockout mice (by 12.9% and 33.6% respectively), while the expression of antiapoptotic protein Bcl-2 has no significant difference between two groups, as shown in Figure 1B–D. To test the influence of ATP13A2 knockout on the infarct size, mice were sacrificed 24 h after MCAO. Brain slices were prepared and stained with 1% 2,3,5-triphenyltetrazolium chloride (TTC). The infarct size was measured with an image analyzer. Our results showed that there was no significant difference in infarct size between ATP13A2 knockout mice and corresponding wild-type mice, as shown in Figure 2. Studies have shown that the pathophysiology of ischemic stroke involves a number of mechanisms, including necrosis, apoptosis, inflammation, excitotoxicity, and free radical damage. In this study, we found that both apoptosis and autophagy were increased in ATP13A2 knockout mice. In fact, when autophagy occurs in excess, it becomes cytotoxic and eventually leads to autophagic cell death and apoptosis [10]. However, the infarct size

Nitric oxide (NO) plays an important role in the pathogenesis of endotoxic shock. This work tested the hypothesis that ketanserin could attenuate endotoxic shock by inhibiting the expression of inducible NO synthase (iNOS). The results demonstrated that ketanserin could inhibit iNOS expression in the heart, lungs, liver, and kidneys and nitrate production in the serum upon endotoxic shock in mice. In RAW264.7 cells, ketanserin significantly inhibited the expression of iNOS and decreased the production of NO, TNFα, IL-6, and reactive oxygen species upon lipopolysaccharide (LPS) challenge. Ketanserin also increased the level of ATP and mitochondrial membrane potential in RAW264.7 cells upon LPS exposure. LPS-induced iNOS expression was inhibited by the 5-HT2A receptor antagonist ritanserin and not the α1 receptor antagonist prazosin. Knockdown of 5-HT2A receptor by siRNA abolished the inhibitory effect of ketanserin on the expression of iNOS. These results indicated that the inhibitory effect of ketanserin on the expression of iNOS is mediated by blocking the 5-HT2A receptor. Furthermore, ketanserin significantly inhibited the activation of ERK1/2 and NF-κB signal. Pretreatment with PD184352, a specific inhibitor of ERK1/2, blocked the inhibitory effect of ketanserin on the expression of iNOS and NO production, indicating a critical role for the MEK/ERK1/2 signaling pathway. Collectively, our findings indicate that inhibition of the expression of iNOS via the MEK/ERK pathway mediates the protective effects of ketanserin against LPS-induced shock in mice.

Background Ketanserin, a 5-hydroxytryptamine receptor antagonist, is clinically used as an antihypertensive agent and could enhance baroreflex function. The present work tested the hypothesis that restoration of baroreflex function is an effective treatment for lipopolysaccharide (LPS)-induced shock. Methods Kunming mice were injected with LPS (30 mg/kg; intraperitoneal) to induce endotoxic shock. Ketanserin (0.3, 1, 3, or 10 mg/kg; intraperitoneal) was administered immediately after LPS injection. Survival time was monitored, and serum cytokines were analyzed after the onset of LPS. Effects of ketanserin were also examined in IL-10-deficient mice and mice with sinoaortic denervation. Finally, effects of ketanserin on blood pressure, heart rate, and baroreflex sensitivity were examined in Wistar-Kyoto (WKY) rats with endotoxic shock. Results Ketanserin significantly increased survival time and decreased serum levels of tumor necrosis factor α and interleukin (IL) 1β in mice with endotoxic shock. At a dose of 10 mg/kg, ketanserin also significantly increased serum IL-10 concentration. The antishock effect of ketanserin was also apparent in IL-10-knockout mice. In mice with sinoaortic denervation, however, ketanserin had little antishock effects. In WKY rats, ketanserin significantly prevented the baroreflex impairment induced by LPS and prolonged the survival time. Conclusions Ketanserin could ameliorate endotoxic shock by restoring baroreflex function.

OBJECTIVES This study was designed to evaluate the interaction between aging and obesity on cardiac contractile and intracellular Ca2+ properties. METHODS Cardiomyocytes from young (4-mo) and aging (12- and 18-mo) male lean and the leptin deficient ob/ob obese mice were treated with leptin (0.5, 1.0 and 50 nM) for 4 hrs in vitro. High fat diet (45% calorie from fat) and the leptin receptor mutant db/db obesity models at young and older age were used for comparison. Cardiomyocyte contractile and intracellular Ca2+ properties were evaluated including peak shortening (PS), maximal velocity of shortening/relengthening (+/- dL/dt), time-to-PS (TPS), time-to-90% relengthening (TR(90)), intracellular Ca2+ levels and decay. O2(-) levels were measured by dihydroethidium fluorescence. RESULTS Our results revealed reduced survival in ob/ob mice. Aging and obesity reduced PS, +/- dL/dt, intracellular Ca2+ rise, prolonged TR(90) and intracellular Ca2+ decay, enhanced O2(-) production and p(47phox) expression without an additive effect of the two, with the exception of intracellular Ca2+ rise. Western blot analysis exhibited reduced Ob-R expression and STAT-3 phosphorylation in both young and aging ob/ob mice, which was restored by leptin. Aging and obesity reduced phosphorylation of Akt, eNOS and p38 while promoting pJNK and pIkappaB. Low levels of leptin reconciled contractile, intracellular Ca2+ and cell signaling defects as well as O2(-) production and p(47phox) upregulation in young but not aging ob/ob mice. High level of leptin (50 nM) compromised contractile and intracellular Ca2+ response as well as O2(-) production and stress signaling in all groups. High fat diet-induced and db/db obesity displayed somewhat comparable aging-induced mechanical but not leptin response. CONCLUSIONS Taken together, our data suggest that aging and obesity compromise cardiac contractile function possibly via phosphorylation of Akt, eNOS and stress signaling-associated O2(-) release.

Aim: To test the effects of atenolol and amlodipine, either alone or in combination, on blood pressure, blood pressure variability (BPV), baroreflex sensitivity (BRS), and the prevalence of stroke in stroke-prone spontaneously hypertensive rats (SHR-SP). Methods: In the first set of the study, 24 8-month-old, female SHR-SP rats were randomly divided into 3 groups. Blood pressure, heart period, and BRS were determined before and after the intragastric administration of atenolol (10 mg/kg) and amlodipine (1.0 mg/kg), either alone or in combination. In the second set of the study, 40 male and 40 female rats were randomly assigned to 1 of the following 4 groups: control, atenolol (10 mg·kg -1 ·d -1 ), amlodipine (1.0 mg·kg -1 ·d -1 ), and both (10 male and 10 female in each group). The stroke incident and survival time were recorded. Results: Atenolol and amlodipine, either alone or in combination, significantly decreased blood pressure, with the exception of the amlodipine-induced effect on diastolic blood pressure. Meanwhile, only the combination treatment significantly decreased the BPV levels for the same period. The q-values calculated by the probability sum analysis were 1.17 and 2.67 for systolic and diastolic blood pressure, respectively, and were 2.48 and 2.10 for systolic and diastolic BPV, respectively, following administration. Neither drug exhibited any significant effect on BRS. Atenolol and amlodipine, either alone or in combination, significantly increased the lifespan of SHR-SP, with the best effect elicited by the combination therapy. Conclusion: A significant synergism exists between atenolol and amlodipine in lowering and stabilizing blood pressure in SHR-SP. Combination therapy may be an optimal strategy for the prevention of stroke in hypertension.

The present work was designed to establish a novel animal model for motion sickness (MS) in rodents and to evaluate the effects of a combination of scopolamine and modafinil on MS with this novel method. It was found that the rats and mice presented several symptoms induced by rotation such as, piloerection, tremble, urinal and fecal incontinence. As the rats and mice are lack of emesis response to rotation, we used a score based on abovementioned symptoms as an index for the severity of MS in rodents. MS index was determined in 260 mice with this novel method. It was found that the distribution of MS index was normal (W=0.99; P=0.23. P>0.05 considered values' normal distribution). The effects of scopolamine on MS were studied in mice and rats. It was found that scopolamine significantly decreased MS index at the dose of 0.3 mg/kg in mice and 1.0 mg/kg in rats. Finally, the effects of a combination of scopolamine and modafinil were observed with this novel method in rats. It was found that the efficacy of the combination (5.0+5.0 mg/kg) was greater than the single drugs (10 mg/kg). Even the smallest dose of the combination (0.5+0.5 mg/kg) had a similar effect to large dose of scopolamine or modafinile when they were used alone. In conclusion, this animal model is suitable for MS study in rats and mice and the combination of scopolamine and modafinil might be a new method to treat or prevent MS.

OCI-5, the rat homologene of human glypican 3 (GPC3), is confirmed upregulated in hepatocellular carcinoma (HCC). The present study was undertaken to detect gene expression change of OCI-5 during occurrence and progression of rat HCC.Male Sprague-Dawley rats were given diethylnitrosamine (DENA) to induce HCC. Three DENA-induced rats and one control rat were sacrificed every week for 18 weeks during the development of HCC. Tissues specimens were snap-frozen in liquid nitrogen and total RNA was isolated. Sk-Hep1 cells were treated with DENA at different concentrations. The gene expression levels of OCI-5 and GPC3 were detected with the RT-PCR method.OCI-5 was not expressed in normal rat liver tissues. When HCC occurred and aggravated, OCI-5 expression was gradually elevated to a very high level. GPC3 was not expressed in the DENA-treated Sk-Hep1 cells.OCI-5 was not expressed in normal rat liver tissues but in rat HCC tissues. High-expression of OCI-5 in DENA-induced rat HCC model was the gene expression change of HCC not the DENA-induced gene expression. The expression level of OCI-5 was not only elevated in rat HCC but also gradually along the occurrence and progression of HCC, indicating that GPC3 might serve as a sensitive marker of early stage HCC.

The present study was designed to test the hypothesis that arterial baroreflex dysfunction promotes the development of atherosclerosis. Experiment 1: the baroreflex sensitivity (BRS) was measured in 30 Sprague-Dawley (SD) rats in conscious state with a computerized blood pressure monitoring system. Four weeks later, the rats were administered with Vitamin D3, and fed with the high-cholesterol diet for 8 weeks to induce atherosclerosis. The hearts and aortae were removed for pathological examination. A negative correlation was found between BRS and the scores of coronary (r=-0.464, P

Activation of the slag cement was performed using a composite activator. Experimental results show that the performance of the cement is remarkably improved. The fineness and specific surface area of the cement are increased by 23.7% and 1.4%, and 3 d flexural strength and compressive strength are enhanced by 20.9% and 22.9%, respectively. Microstructure and phase composition of the hydrates were analysed by X-ray diffraction (XRD) and scanning electron microscopy (SEM). The results indicate that Ca(OH)2 in the hydrates decrease obviously. The morphology of the other hydrates appears to be flocculent, with a dense structure. The improvements of the properties is related to the microstructural changes.