Treadmill exercise improves hippocampal neural plasticity and relieves cognitive deficits in a mouse model of epilepsy

Epilepsy frequently leads to cognitive dysfunction and approaches to treatment remain limited.Although regular exercise effectively improves learning and memory functions across multiple neurological diseases,its application in patients with epilepsy remains controversial.Here,we adopted a 14-day treadmill-exercise paradigm in a pilocarpine injection-induced mouse model of epilepsy.Cognitive assays confirmed the improvement of object and spatial memory after endurance training,and electrophysiological studies revealed the maintenance of hippocampal plasticity as a result of physical exercise.Investigations of the mechanisms underlying this effect revealed that exercise protected parvalbumin interneurons,probably via the suppression of neuroinflammation and improved integrity of blood-brain barrier.In summary,this work identified a previously unknown mechanism through which exercise improves cognitive rehabilitation in epilepsy.

Exercise preconditioning alleviates ischemia-induced memory deficits by increasing circulating adiponectin

Cerebral ischemia is a major health risk that requires preventive approaches in addition to drug therapy.Physical exercise enhances neurogenesis and synaptogenesis,and has been widely used for functional rehabilitation after stroke.In this study,we determined whether exercise training before disease onset can alleviate the severity of cerebral ischemia.We also examined the role of exercise-induced circulating factors in these effects.Adult mice were subjected to 14 days of treadmill exercise training before surgery for middle cerebral artery occlusion.We found that this exercise pre-conditioning strategy effectively attenuated brain infarct area,inhibited gliogenesis,protected synaptic proteins,and improved novel object and spatial memory function.Further analysis showed that circulating adiponectin plays a critical role in these preventive effects of exercise.Agonist activation of adiponectin receptors by Adipo Ron mimicked the effects of exercise,while inhibiting receptor activation abolished the exercise effects.In summary,our results suggest a crucial role of circulating adiponectin in the effects of exercise pre-conditioning in protecting against cerebral ischemia and supporting the health benefits of exercise.

Enhancement of motor functional recovery in thoracic spinal cord injury: voluntary wheel running versus forced treadmill exercise

Spinal cord injury necessitates effective rehabilitation strategies, with exercise therapies showing promise in promoting recovery. This study investigated the impact of rehabilitation exercise on functional recovery and morphological changes following thoracic contusive spinal cord injury. After a 7-day recovery period after spinal cord injury, mice were assigned to either a trained group(10 weeks of voluntary running wheel or forced treadmill exercise) or an untrained group. Bi-weekly assessments revealed that the exercise-trained group, particularly the voluntary wheel exercise subgroup, displayed significantly improved locomotor recovery, more plasticity of dopaminergic and serotonin modulation compared with the untrained group. Additionally, exercise interventions led to gait pattern restoration and enhanced transcranial magnetic motor-evoked potentials. Despite consistent injury areas across groups, exercise training promoted terminal innervation of descending axons. In summary, voluntary wheel exercise shows promise for enhancing outcomes after thoracic contusive spinal cord injury, emphasizing the role of exercise modality in promoting recovery and morphological changes in spinal cord injuries. Our findings will influence future strategies for rehabilitation exercises, restoring functional movement after spinal cord injury.

Treadmill exercise in combination with acousto-optic and olfactory stimulation improves cognitive function in APP/PS1 mice through the brain-derived neurotrophic factor-and Cygb-associated signaling pathways

A reduction in adult neurogenesis is associated with behavioral abnormalities in patients with Alzheimer's disease.Consequently,enhancing adult neurogenesis represents a promising therapeutic approach for mitigating disease symptoms and progression.Nonetheless,nonpharmacological interventions aimed at inducing adult neurogenesis are currently limited.Although individual non-pharmacological interventions,such as aerobic exercise,acousto-optic stimulation,and olfactory stimulation,have shown limited capacity to improve neurogenesis and cognitive function in patients with Alzheimer's disease,the therapeutic effect of a strategy that combines these interventions has not been fully explored.In this study,we observed an age-dependent decrease in adult neurogenesis and a concurrent increase in amyloid-beta accumulation in the hippocampus of amyloid precursor protein/presenilin 1 mice aged 2-8 months.Amyloid deposition became evident at 4 months,while neurogenesis declined by 6 months,further deteriorating as the disease progressed.However,following a 4-week multifactor stimulation protocol,which encompassed treadmill running(46 min/d,10 m/min,6 days per week),40 Hz acousto-optic stimulation(1 hour/day,6 days/week),and olfactory stimulation(1 hour/day,6 days/week),we found a significant increase in the number of newborn cells(5'-bromo-2'-deoxyuridine-positive cells),immature neurons(doublecortin-positive cells),newborn immature neurons(5'-bromo-2'-deoxyuridine-positive/doublecortin-positive cells),and newborn astrocytes(5'-bromo-2'-deoxyuridine-positive/glial fibrillary acidic protein-positive cells).Additionally,the amyloid-beta load in the hippocampus decreased.These findings suggest that multifactor stimulation can enhance adult hippocampal neurogenesis and mitigate amyloid-beta neuropathology in amyloid precursor protein/presenilin 1 mice.Furthermore,cognitive abilities were improved,and depressive symptoms were alleviated in amyloid precursor protein/presenilin 1 mice following multifactor stimulation,as evidenced by Morris water maze,novel object recognition,forced swimming test,and tail suspension test results.Notably,the efficacy of multifactor stimulation in consolidating immature neurons persisted for at least 2weeks after treatment cessation.At the molecular level,multifactor stimulation upregulated the expression of neuron-related proteins(NeuN,doublecortin,postsynaptic density protein-95,and synaptophysin),anti-apoptosis-related proteins(Bcl-2 and PARP),and an autophagyassociated protein(LC3B),while decreasing the expression of apoptosis-related proteins(BAX and caspase-9),in the hippocampus of amyloid precursor protein/presenilin 1 mice.These observations might be attributable to both the brain-derived neurotrophic factor-mediated signaling pathway and antioxidant pathways.Furthermore,serum metabolomics analysis indicated that multifactor stimulation regulated differentially expressed metabolites associated with cell apoptosis,oxidative damage,and cognition.Collectively,these findings suggest that multifactor stimulation is a novel non-invasive approach for the prevention and treatment of Alzheimer's disease.

Treadmill exercise exerts a synergistic effect with bone marrow mesenchymal stem cell-derived exosomes on neuronal apoptosis and synaptic-axonal remodeling

Treadmill exercise and mesenchymal stem cell transplantation are both practical and effective methods for the treatment of cerebral ischemia.However,whether there is a synergistic effect between the two remains unclear.In this study,we established rat models of ischemia/reperfusion injury by occlusion of the middle cerebral artery for 2 hours and reperfusion for 24 hours.Rat models were perfused with bone marrow mesenchymal stem cell-derived exosomes(MSC-exos)via the tail vein and underwent 14 successive days of treadmill exercise.Neurological assessment,histopathology,and immunohistochemistry results revealed decreased neuronal apoptosis and cerebral infarct volume,evident synaptic formation and axonal regeneration,and remarkably recovered neurological function in rats subjected to treadmill exercise and MSC-exos treatment.These effects were superior to those in rats subjected to treadmill exercise or MSC-exos treatment alone.Mechanistically,further investigation revealed that the activation of JNK1/c-Jun signaling pathways regulated neuronal apoptosis and synaptic-axonal remodeling.These findings suggest that treadmill exercise may exhibit a synergistic effect with MSC-exos treatment,which may be related to activation of the JNK1/c-Jun signaling pathway.This study provides novel theoretical evidence for the clinical application of treadmill exercise combined with MSC-exos treatment for ischemic cerebrovascular disease.

Rehabilitation following spinal cord injury:how animal models can help our understanding of exercise-induced neuroplasticity

Spinal cord injury is a devastating condition that is followed by long and often unsuccessful recovery after trauma. The state of the art approach to manage paralysis and concomitant impairments is rehabilitation, which is the only strategy that has proven to be effective and beneficial for the patients over the last decades. How rehabilitation influences the remodeling of spinal axonal connections in patients is important to understand, in order to better target these changes and define the optimal timing and onset of training. While clinically the answers to these questions remain difficult to obtain, rodent models of rehabilitation like bicycling, treadmill training, swimming, enriched environments or wheel running that mimic clinical rehabilitation can be helpful to reveal the axonal changes underlying motor recovery. This review will focus on the different animal models of spinal cord injury rehabilitation and the underlying changes in neuronal networks that are improved by exercise and rehabilitation.

Abnormal ground reaction forces lead to a general decline in gait speed in knee osteoarthritis patients

AIM To analyse ground reaction forces at higher speeds using another method to be more sensitive in assessing significant gait abnormalities. METHODS A total of 44 subjects, consisting of 24 knee osteoarthritis(OA) patients and 20 healthy controls were analysed. The knee OA patients were recruited from an orthopaedic clinic that were awaiting knee replacement. All subjects had their gait patterns during stance phase at top walking speed assessed on a validated treadmill instrumented with tandem force plates. Temporal measurements and ground reaction forces(GRFs) along with a novel impulse technique were collected for both limbs and a symmetry ratio was applied to all variables to assess inter-limb asymmetry. All continuous variables for each group were compared using a student t-test and χ2 analysis for categorical variables with significance set at α = 0.05. Receiver operator characteristics curves were utilised to determine best discriminating ability.RESULTS The knee OA patients were older(66 ± 7 years vs 53 ± 9 years, P = 0.01) and heavier(body mass index: 31 ± 6 vs 23 ± 7, P < 0.001) but had a similar gender ratio when compared to the control group. Knee OA patients were predictably slower at top walking speed(1.37 ± 0.23 m/s vs 2.00 ± 0.20 m/s, P < 0.0001) with shorter mean step length(79 ± 12 cm vs 99 ± 8 cm, P < 0.0001) and broader gait width(14 ± 5 cm vs 11 ± 3 cm, P = 0.015) than controls without any known lower-limb joint disease. At a matched mean speed(1.37 ± 0.23 vs 1.34 ± 0.07), ground reaction results revealed that pushoff forces and impulse were significantly(P < 0.0001) worse(18% and 12% respectively) for the knee OA patients when compared to the controls. Receiver operating characteristic curves analysis demonstrated total impulse to be the best discriminator of asymmetry, with an area under the curve of 0.902, with a cut-off of-3% and a specificity of 95% and sensitivity of 88%.CONCLUSION Abnormal GRFs in knee osteoarthritis are clearly evident at higher speeds. Analysing GRFs with another method may explain the general decline in knee OA patient's gait.

Rehabilitation training improves exercise tolerance after percutaneous coronary intervention

The aim of this present study was to investigate the effects of training on exercise tolerance of patients with coronary heart disease after percutaneous coronary intervention.Fifty-seven cases of coronary heart disease after percutaneous coronary intervention were divided randomly into the rehabilitation training group（26 cases） and control group（31 cases）.Patients in the rehabilitation training group received rehabilitation training at different stages and exercise intensities 3 d after percutaneous coronary intervention for 3 months.The heart rate,blood pressure,ECG changes in treadmill exercise test,and the frequency of anginal episodes were observed.The results showed that NST and ΣST of ECG and the frequency of anginal episodes were significantly reduced in the rehabilitation training group.In addition,exercise tolerance was improved and the total exercise time was lengthened in these patients.Moreover,ST segment depression time and emergence time of angina with exercise were also lengthened compared with controls（P 〈 0.05,or 0.01）.However,the heart rate and blood pressure before and after exercise of the two groups were similar.The study indicated that rehabilitation training could significantly relieve angina,amend ischemic features of ECG,and improve exercise tolerance of coronary heart disease patients after percutaneous coronary intervention.

Paternal physical exercise modulates global DNA methylation status in the hippocampus of male rat offspring

It is widely known that maternal physical exercise is able to induce beneficial improvements in offspring cognition; however, the effects of paternal exercise have not been explored in detail. The present study was designed to evaluate the impact of paternal physical exercise on memory and learning, neuroplasticity and DNA methylation levels in the hippocampus of male offspring. Adult male Wistar rats were divided into two groups: sedentary or exercised fathers. The paternal preconception exercise protocol consisted of treadmill running, 20 minutes daily, 5 consecutive days per week for 22 days, while the mothers were not trained. After mating, paternal sperm was collected for global DNA methylation analysis. At postnatal day 53, the offspring were euthanized, and the hippocampus was dissected to measure cell survival by 5-bromo-2′-deoxiuridine and to determine the expression of synaptophysin, reelin, brain-derived neurotrophic factor and global DNA methylation levels. To measure spatial memory and learning changes in offspring, the Morris water maze paradigm was used. There was an improvement in spatial learning, as well as a significant decrease in hippocampal global DNA methylation levels in the offspring from exercised fathers compared with those from sedentary ones; however, no changes were observed in neuroplasticity biomarkers brain-derived neurotrophic factor, reelin and 5-bromo-2′-deoxiuridine. Finally, the global DNA methylation of paternal sperm was not significantly changed by physical exercise. These results suggest a link between paternal preconception physical activity and cognitive benefit, which may be associated with hippocampal epigenetic programming in male offspring. However, the biological mechanisms of this modulation remain unclear.

Treadmill training improves neurological deficits and suppresses neuronal apoptosis in cerebral ischemic stroke rats

RehabilNation training is believed to be beneficial to patients with stroke, but its molecular mechanism is still unclear. Rat models of cerebral ischemic stroke were established by middle cerebral artery occlusion/reperfusion, and then received treadmill training of different intens让ies, twice a day for 30 minutes for 1 week. Low-intensity training was conducted at 5 m/min, with a 10-minute running, 10-minute rest, and 10-minute running cycle. In the moderate-intensity training, the intensity gradually increased from 5 m/min to 10 m/min in 5 minutes, with the same rest cycle as above. In high-intensity training, the intensity gradually increased from 5 m/min to 25 m/min in 5 minutes, with the same rest cycle as above. The Bederson scale was used to evaluate the improvement of motor function. Infarct volume was detected using 2,3,5-triphenyltetrazolium chloride staining. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining was applied to detect the apoptosis of nerve cells in brain tissue. Western blot assay was employed to analyze the activation of cyclic adenosine monophosphate (cAMP)/protein kinase A and Akt/glycogen synthase kinase-3卩 signaling pathways in rat brain tissue. All training intensities reduced the neurological deficit score, infarct volume, and apoptosis in nerve cells in brain tissue of stroke rats. Training intensities activated the cAMP/protein kinase A and Akt/glycogen synthase kinase-3 beta signaling pathways. This activation was more obvious with higher training intensities. These changes were reversed by intracerebroventricular injection of protein kinase A inhibitor Rp-cAMP. Our findings indicate that the neuroprotective effect of rehabilitation training is achieved via activation of the cAMP/ protein kinase A and Akt/glycogen synthase kinase-3 beta signaling pathways. This study was approved by the Ethics Committee of Animal Experimentation in Shanghai No. 8 Peoples Hospital, China.

Chronic exercise training versus acute endurance exercise in reducing neurotoxicity in rats exposed to lead acetate

After intraperitoneal injection of 20 mg/kg lead acetate, rats received 8 weeks of treadmill exercise （15-22 m/min, 25-64 minutes） and/or treadmill exercise at 1.6 km/h until exhaustion. The markers related to neurotoxicity were measured by enzyme-linked immunosorbent assay method. 8 weeks of treadmill exercise significantly increased brain-derived neurotrophic factor level in the hippocampus （P = 0.04） and plasma level of total antioxidant capacity of rats exposed to lead acetate （P 〈 0.001）, and significantly decreased plasma level of malondialdehyde （P 〈 0.001）. Acute exercise only decreased the hippocampal malondialdehyde level （P = 0.09） and increased brain-derived neurotrophic factor level in the hippocampus （P = 0.66）. Acute exercise also enhanced the total antioxidant capacity in rats exposed to lead acetate, insignificantly （P = 0.99）, These findings suggest that chronic treadmill exercise can significantly decrease neurotoxicity and alleviate oxidative stress in rats exposed to lead acetate. However, acute endurance exercise was not associated with these beneficial effects.

Regional cerebral blood flow imaging assessment of brain function reconstruction in elderly hemiplegia patients by body weight support treadmill training

The mechanism underlying body weight support treadmill training in elderly hemiplegic stroke patients is largely unknown. This study aimed to elucidate the changes of cortical blood flow in seven elderly patients with post-stroke hemiplegia before and after body weight support treadmill training by semi-quantitative analysis of regional cerebral blood flow assessed by single photon emission computed tomography. Body weight support treadmill training for 6 months was effective in improving cerebral blood flow and promoting the walking speed and balance recovery in elderly patients with post-stroke hemiplegia.

Inhalation of shin-I essential oil enhances lactate clearance in treadmill exercise

Objective:To evaluate the effect of Shin-I essential oil inhalation on blood lactate changes in rats subjected to treadmill exercise.Methods:Adult male Sprague Dawley rats(n=12) were randomly divided into the control or the Shin—1 group.Rats were subjected to a treadmill exercise program(15 m/min for 30 mim.After exercise,rats were exposed to 200 ui.of water or Shin—I essential oil.res|ieclively.using a nebulizer for 180 min during the recovery period.Blood samples were collected every 15 min.Blood glucose and lactate concentrations were determined in a CMA 600 analyzer.Results:The basal glucose and lactate levels wen? no significantly different between two groups.After exercise,glucose levels were slightly increased to about 110%-120%of the basal level in both groups.lactate levels of both groups reached to 110%-140%of basal levels during exercise.In the recovery period,lactate levels further increased to 180%of the basal level and were maintained at a plateau in the control group.However,lactate levels gradually decreased to 609—657 of the basal level in the Shin-I group.Lactate clearance was significantly enhanceil after Shin-I essential oil inhalation.Conclusions:Our results provide evidence that Shin-I essential oil inhalation may accelerate recovery after exercise in rats.

Neurorehabilitation using a voluntary driven exoskeletal robot improves trunk function in patients with chronic spinal cord injury: a single-arm study

Body weight-supported treadmill training with the voluntary driven exoskeleton(VDE-BWSTT) has been shown to improve the gait function of patients with chronic spinal cord injury. However, little is known whether VDE-BWSTT can effectively improve the trunk function of patients with chronic spinal cord injury. In this open-label, single-arm study, nine patients with chronic spinal cord injury at the cervical or thoracic level(six males and three females, aged 37.8 ± 15.6 years, and time since injury 51.1 ± 31.8 months) who underwent outpatient VDE-BWSTT training program at Keio University Hospital, Japan from September 2017 to March 2019 were included. All patients underwent twenty 60-minute gait training sessions using VDE. Trunk muscular strength, i.e., the maximum force against which patient could maintain a sitting posture without any support, was evaluated in four directions: anterior, posterior, and lateral(right and left) after 10 and 20 training sessions. After intervention, lateral muscular strength significantly improved. In addition, a significant positive correlation was detected between the change in lateral trunk muscular strength after 20 training sessions relative to baseline and gait speed. The change in trunk muscular strength after 20 training sessions relative to baseline was greatly correlated with patient age. This suggests that older adult patients with chronic spinal cord injury achieved a greater improvement in trunk muscle strength following VDE-BWSTT. All these findings suggest that VDE-BWSTT can improve the trunk function of patients with chronic spinal cord injury and the effect might be greater in older adult patients. The study was approved by the Keio University of Medicine Ethics Committee(IRB No. 20150355-3) on September 26, 2017.

Dynamic biomechanical effect of lower body positive pressure treadmill training for hemiplegic gait rehabilitation after stroke: A case report

BACKGROUND Lower body positive pressure(LBPP)treadmill has potential applications for improving the gait of patients after stroke,but the related mechanism remains unclear.CASE SUMMARY A 62-year-old male patient suffered from ischemic stroke with hemiplegic gait.He was referred to our hospital because of a complaint of left limb weakness for 2 years.The LBPP training was performed one session per day and six times per week for 2 wk.The dynamic plantar pressure analysis was taken every 2 d.Meanwhile,three-digital gait analysis and synchronous electromyography as well as clinical assessments were taken before and after LBPP intervention and at the 4-wk follow-up.During LBPP training,our patient not only improved his lower limb muscle strength and walking speed,but more importantly,the symmetry index of various biomechanical indicators improved.Moreover,the patient’s planter pressure transferring from the heel area to toe area among the LBPP training process and the symmetry of lower body biomechanical parameters improved.CONCLUSION In this study,we documented a dynamic improvement of gait performance in a stroke patient under LBPP training,which included lower limb muscle strength,walking speed,and symmetry of lower limb biomechanics.Our study provides some crucial clues about the potential dynamic mechanism for LBPP training on gait and balance improvement,which is related to rebuilding foot pressure distribution and remodeling symmetry of biomechanics of the lower limb.

Exertional esophageal pH-metry and manometry in recurrent chest pain

AIM: To investigate the diagnostic efficacy of 24-h and exertional esophageal pH-metry and manometry in patients with recurrent chest pain. METHODS: The study included 111 patients (54% male) with recurrent angina-like chest pain, non-respon- sive to therapy with proton pump inhibitors. Sixty-five (59%) had non-obstructive lesions in coronary artery angiography, and in 46 (41%) significant coronary artery narrowing was found. In all patients, 24-h esophageal pH-metry and manometry, and treadmill stress tests with simultaneous esophageal pH-metry and manometry monitoring were performed. During a 24-h examination the percentage of spontaneous chest pain (sCP) episodes associated with acid reflux or dysmotility (symptom index, SI) was calculated. Patients with SI > 50% for acid gastroesophageal reflux (GER) were classified as having GER-related sCP. The remaining symptomatic individuals were determined as having non-GER-related sCP. During the stress test, the occurrence of chest pain, episodes of esophageal acidification (pH < 4 for 10 s) and esophageal spasm with more than 55% of simultaneous contractions (exercise-provoked esophageal spasm or EPES) were noted. RESULTS: Sixty-eight (61%) individuals reported sCP during 24-h esophageal function monitoring. Eleven of these (16%) were classified as having GER-related sCP and 53/68 (84%) as having non-GER-related sCP. The exercise-provoked chest pain during a stress test occurred in 13/111 (12%) subjects. In order to compare the clinical usefulness of 24-h esophageal function monitoring and its examination limited only to the treadmill stress test, the standard parameters of diagnostic test evaluation were determined. The occurrence of GER- related or non-GER-related sCP was assumed as a "gold standard". Afterwards, accuracy, sensitivity and specificity were calculated. These parameters expressed a prediction of GER-related or non-GER-related sCP occurrence by the presence of chest pain, esophageal acidification and EPES. Accuracy, sensitivity and specificity of chest pain during the stress test predicting any sCP occurrence were 28%, 35% and 80%, respectively, predicting GER- related sCP were 42%, 0% and 83%, respectively, and predicting non-GER-related sCP were 57%, 36% and 83%, respectively. Similar values were obtained for exercise-related acidification with pH < 4 longer than 10 s in the prediction of GER-related sCP (44%, 36% and 92%, respectively) and EPES in relation to non-GER-related sCP (48%, 23% and 84%, respectively). CONCLUSION: The presence of chest pain, esophageal acidification and EPES had greater than 80% specificity to exclude the GER-related and non-GER-related causes of recurrent chest pain.

The prospects of regenerative medicine combined with rehabilitative approaches for chronic spinal cord injury animal models

Regenerative medicine has opened a window for functional recovery in acute-to-subacute phase spinal cord injury（SCI）.By contrast,there are still only a few studies have focused on the treatment of the chronically injured spinal cord,in which cell-based regenerative medicine seems less effective.Since the majority of SCI patients are in the chronic phase,representing a major challenge for the clinical application of cellbased regenerative medicine.Although combined therapies for the treatment of chronic SCI have attracted attention of researchers and its potential importance is also widely recognized,there had been very few studies involving rehabilitative treatments to date.In a recent study,we have demonstrated for the first time that treadmill training combined with cell transplantation significantly promotes functional recovery even in chronic SCI,not only in additive but also in synergistic manner.Even though we have succeeded to outline the profiles of recovery secondary to the combination therapy,the mechanism underlying the effects remain unsolved.In this review article,we summarize the present progress and consider the prospect of the cell-based regenerative medicine particularly combined with rehabilitative approaches for chronic SCI animal models.

TWO METHODS TO IMPROVE THE ACCURACY OF TREADMILL EXERCISE TESTING──ANALYSIS OF 147 CASESIN CONTRAST WITH CORONARY ANGIOGRAPHY

objective To study how to improve the accuracy of treadmill exercise testing(TET).Methods TET was performed before coronary angiography (CAG) for 147 subjects admitted into our departmentbecause of suspicion of angina or coronary artery disease (CAD), then: (1) Every subject was inquired about hissymptoms and physically examined in detail before the testing. Chest pain was divided into ischemic (ICP) ornon - ischemic (NICP) pattern. (2) Informations got from TET, like angina, ST segment depression, and SPB ratio,were analyzed in detail. Results (1) When the patients showed chest pain of ICP pattern and positive TETresults, the sensitivity of TET would be 95%, for patients with NICP chest pain, the negative result of TET meansthat their coronary arteries is normal with the accurate possibility of 98%. (2) By our new criteria of TET, thesensitivity and specificity of TET were 89% and 95% respectively, both higher than those in theliterature. Conclusion in this report, we found TET was more sensitive and accurate if we knew the symptomsprior, especially in detail the characteristics of chest pain, and consider different parameters in combination.

Urinary corticosterone and normetanephrine levels after voluntary wheel and forced treadmill running in the db/db mouse

Exercise is recommended for the treatment of type 2 diabetes because of its benefits on body weight and glycemic control. Our recent work using the db/db mouse, a model that mimics the phenotype of type 2 diabetes, demonstrated that forced treadmill training exerted detrimental effects on obesity, hyperglycemia and insulin resistance. We investigated whether this response is explained by increased corticosterone and norepinephrine secretion, measured as urinary byproducts, since these hormones are known to alter glucose homeostasis. Male db/db mice and lean littermates serving as controls, were assigned to sedentary, voluntary wheel, and forced treadmill training groups for a period of 5 weeks. After 5 weeks of treadmill running, db/db mice remained hyperglycemic compared to sedentary db/db mice and were hyperinsulinemic compared to db/db voluntary runners. Urine glucose and corticosterone levels were also highest in db/db treadmill runners compared to all groups. Urine normetanephrine levels, although lower in db/db mice compared to control mice, were increased after treadmill running. Our results indicate that treadmill running leads to perturbations in plasma levels of hormones associated with glucose homeostasis. A greater stress response may be invoked by treadmill training, worsening glycemic control in this model of type 2 diabetes.

Low-intensity Treadmill Exercise Promotes Rat Dorsal Wound Healing

In order to investigate the promoting effect of low-intensity treadmill exercise on rat dorsal wound healing and the mechanism, 20 Sprague-Dawley rats were randomly divided into two groups： exercise group（Ex） and non-exercise group（non-ex）. The rats in Ex group were given treadmill exercise for one month, and those in non-ex group raised on the same conditions without treadmill exercise. Both groups received dorsal wound operation with free access to food and water. By two-week continuous observation and recording of the wound area, the healing rate was analyzed. The blood sample was collected at day 14 post-operation via cardiac puncture for determination of the number of endothelial progenitor cells（EPCs） by flow cytometry, and the concentrations of relevant cytokines such as basic fibroblast growth factor（b FGF）, endothelial nitric oxide synthase（e NOS） and vascular endothelial growth factor（VEGF） were measured by ELISA. The skin tissue around the wound was dissected to observe the vascular density under the microscope after HE staining, to detect the m RNA level of VEGFR2 and angiopoietin-1（Ang-1） receptor using RT-q PCR, and protein expression of α-smooth muscle actin（αSMA） and type collagenⅢ（ColⅢ） using Western blotting. It was found that the wound area in Ex group was smaller at the same time point than in non-ex group. The number of circulating EPCs was greater and the concentrations of vasoactive factors such as VEGF, e NOS and b FGF were higher in Ex group than in non-ex group. HE staining displayed a higher vessel density in Ex group than in non-ex group. Moreover, the m RNA expression of VEGFR2 and Ang-1 detected in the wound tissue in Ex group was higher than in non-ex group. Meanwhile, the protein expression of αSMA and Col Ⅲwas more abundant in Ex group than in non-ex group. Conclusively, the above results demonstrate Ex rats had a higher wound healing rate, suggesting low-intensity treadmill exercise accelerates wound healing. The present work may provide some hint for future study of treating refractory wound.