Objective To investigate abnormal myocardial contractile responses induced by dobutamine in patients with idiopathic dilated cardiomyopathy (DCM).Methods Eighteen DCM patients underwent low dosage dobutamine stress echocardiography (5,10,20 ?g?kg~ -1?min~ -1).Transthoracic echocardiogram was recorded with the use of a HP Sonos 5500 color echocardiographic diagnostic system.Wall motions in 16 myocardial segments were assessed using a four-point scale recommended by the American Society of Echocardiography.During dobutamine infusion,abnormally contracting segments were classified into four different patterns of contractile response: improved,unchanged,worsened and biphasic.Unchanged,worsened and biphasic segments were defined as abnormal contractile responses.Worsened and biphasic segments were judged to be ischemia-like responses.Results All patients showed abnormal myocardial contractile responses of wall motions (100%),and thirteen were ischemia-like responses ( 72.2%).In total 225 segments,126 segments showed abnormal contractile responses ( 56.0%).Among them,97 segments were unchanged segments ( 43.1%),29 segments were ischemia-like responses ( 12.9%),in which 16 segments were worsened ( 7.1%),and 13 segments were biphasic ( 5.8%).The statistical analysis showed that incidence of improved segments was highest in two point segments( 62.1%) compared with three point and four point segments; incidence of ischemia-like responses was highest in three point segments( 24.6%); incidence of unchanged segments was highest in four point segments( 68.4%).Conclusions DCM has the abnormal myocardial contractile responses induced by dobutamine stress echocardiography.It indicates there is the ischemia-like energy mismatch between demand and supply in DCM,which would be related to etiology and progress of DCM.

Objective To investigate whether dobutamine could induce or worsen electromechanical activity synchronism in the patients with idiopathic dilated cardiomyopathy(DCM). Methods Eighteen patients with DCM[mean age ( 45.8 ? 13.9 ) years, NYHA class Ⅱ-Ⅲ, left ventricular ejection fraction(LVEF)

AIM: To set up population pharmacokinetics/pharmacodynamics (PPK/PD) model of valproate (VPA) in children with epilepsy in China, and promote reasonable use of antiepileptic drugs(AEDs)in clinical practice. METHODS: Sparse data of VPA serum concentrations from 246 pediatric children were collected. These patients were divided into three groups: PPK-Model group ([WTBX]n=146), to calculate PPK parameter values of VPA and set up a PPK model; PPK-Valid group ([WTBX]n=100), to valid the PPK model; and PPD group ([WTBX]n=69), to set up PPK/PD model. Based on the data of PPK-Model group and PPK-Valid group, a PPK model of VPA in children with epilepsy in China was successfully set up by using NONMEM software by ourselves. Now, using the data of 69 patients in PPD group who were on VPA monotherapy and this PPK model, we set up PPK/PD model by NONMEM software. Efficacy of epilepsy treatment was divided into 5 grades according to the percentage of seizure frequency decreased (PSFD%): grade 1: PSFD% was 100%; grade 2: PSFD% was 75%-100%; grade 3: PSFD% was 50%-75%; grade 4: PSFD% was 25%-50%; grade 5: PSFD% was less than 25%. The quantitive relationship between the VPA serum concentrations and the probability for its efficacy score was characterized by Logistic regression analysis with NONMEM. RESULTS: Logistic regression analysis showed that, VPA serum concentrations and the probability for its efficacy grades 5, 4, 3, 2, and 1 were (23 ?g?ml -1, 5, 50%), (30 ?g?ml -1, 4, 32.3%), (50 ?g?ml -1, 3, 26.3%), (65 ?g?ml -1, 2, 36.5%), (78 ?g?ml -1, 1, 50%), and (100 ?g?ml -1, 1, 84.2%)respectively. CONCLUSION: A PPK/PD model of VPA in children with epilepsy in China is successfully established by using NONMEM software, and the probability of efficacy grade for any concentration can be calculated. It will be valuable to facilitate individualized dosage regimen.

Sleep and memory are the basic function of the brain. A large number of studies from both humans and animals experiments have offered a substantive body of evidence supporting that sleep contributes crucially to memory consolidation. The processes of memory consolidation in hippocampus and cortex during sleep was reviewed and the primary cellular and molecular mechanism were briefly introduced.

BACKGROUND:Apoptosis,which result in various reasons,plays an important role in intervertebral disc degeneration. One of important reasons for apoptosis is oxidative stress. OBJECTIVE:To investigate effects and mechanism of hydrogen-peroxide(H2O2) on nucleus pulposus cell injury induced by oxidative stress at intracellular signal transduction level in rats. DESIGN,TIME AND SETTING:A single sample observation was performed at the institute of Traumatology and Orthopaedics of Shandong Province from March to October in 2008. MATERIALS:The specific p38 mitogen-activated protein kinase(p38 MAPK) inhibitor SB203580,the specific JNK inhibitor SP600125 were purchased from Beyotime Institute of Biotechnology;Two 24-hour-old SD rats of SPF degree were purchased from Qingdao Institute for Drug Control. METHODS:The primary cultured nucleus pulposus cells were divided into four groups:the H2O2 group,stimulated by H2O2 with concentrations of 0,50,100,200,400,and 800 ?mol/L;Control group;SB203580+H2O2 group:cells were preincubated with SB203580,and then were treated by stimulated by H2O2;SP600125+H2O2 group,cells were preincubated with SP600125,followed by stimulated by H2O2. MAIN OUTCOME MEASURES:The expression and cellular localization of P-p38MAPK and P-JNK was detected by immunohistochemistry,and the expression of total and phosphorylated SAPK/JNK,p38MAPK were measured by Western blotting. RESULTS:H2O2 could activate the activity of P38 and JNK. The expression of P38MAPK was significantly inhibited with the pretreatment of SB203580;however,the SP600125 could inhibit the expression of JNK. Immunofluorescence analysis demonstrated that P-p38MAPK and P-JNK were expressed and distributed mainly in cytoplasmic and nuclear exception of the control group. CONCLUSIONS:Apoptosis of rat nucleus pulposus cells are induced by oxidative stress via p38MAPK and JNK signal pathway.

[Objective]To study the pathogenesis,clinical manifestation and surgical treatment of the posterior margin separation of lumbar vertebral epiphysis.[Method]Sixteen patients suffering from the posterior margin separation of lumbar vertebral epiphysis were followed up.The clinical manifestation and radiologic examination were analyzed and results of surgical treatment were evaluated.[Result]The patients were usually young and manifested with the sign and symptom of lumbar disc herniation and/or lumbar stenosis.CT was helpful for the accurate diagnosis of this disease.The different surgical measures were taken for the treatment according to the type and range of protrusion.[Conclusion]The posterior margin separation of lumbar vertebral epiphysis were divided into three types:end plate separation and moving into posterior margin,Schmorl node and avulsion fracture.The good results can be obtained with surgery.

Objective To study the biological effects of pSNAV2-hTGF?1 and pSNAV2-hTGF?3 on the reversion of rabbit disc degeneration. Methods Rabbit nucleus pulpous and annulus fibrosus cells were isolated and cultured. The fluorescence labled pSNAV2 were used to detect the transfect rates of rabbit disc cells at first. Then, the pSNAV2-hTGF?1 and pSNAV2-hTGF?3 were transfected into the degenerated rabbit disc cells respectively. The biological effects of hTGF?1 and hTGF?3 on degenerated rabbit disc cells were detected with Western-bloting and 35S detection to analyze and compare the matrix synthesis of the tranfected cells. Results pSNAV2 could transfect degenerated disc cells effectively in the early stages. Both the pSNAV2-hTGF?1 and pSNAV2-hTGF?3 could stimulate the synthesis of collagen Ⅱ and proteoglycan of the rabbit disc cells. For the early stage of degenerated disc cells, the synthesis of collagen Ⅱ and proteoglycan were greater transfected with pSNAV2-hTGF?1 than transfected with pSNAV2-hTGF?3. The pSNAV2-hTGF?1 could promote the degenerated rabbit annulus fibrosus cells to synthesize collagen Ⅰ and pSNAV2-hTGF?3 could promote the degenerated nucleus pulpous cells of later stage to synthesize the collagen Ⅱ. Conclusion Both pSNAV2-hTGF?1 and pSNAV2-hTGF?3 can promote the degenerated rabbit disc cells of early stage to synthesize the matrix. pSNAV2-hTGF?3 can efficently promote the seriously degenerated nucleus pulpous cells to synthesize the collagen Ⅱ.

Objective To study the method of isolating and culturing stem cells from rat adipose tissue and to determine if adipose-derived stem cells(ADSCs)harvest from rat could differentiate into osteogenic and chondrogenic in vitro.Methods ADSCs were isolated from rat inguinal fat pads after extensive washing with phosphate-derived saline and digesting with collagenase.After primary culture in control medium and expanded to two passages,the cells were incubated in either an osteogenic medium or an chondrogenic medium for 2-4 weeks to induce osteogenesis and chondrogenesis,respectively.Evidences of Osteogenic differentiation,were detected by a ALP solution,and while chondrogenic differentiation was confirmed using the histologic Alcian blue staining at acidic pH.Expressions of osteocyte and chondrocyte specific genes were confirmed by RT-PCR.Results ADSCs can be isolated from rat adipose tissue and,expanded rapidly.It exhibited a heterogeneous population of fibroblast like cells morphologically.ADSCs induced to osteogenesis were stained positively for alkaline phosphatase activity after 2 weeks and formed mineralized nodular structures,as conformed by Von kossa staining.Expression of osteocyte specific genes,such as ALP,osteopontin,osteocalcin,was detected.ALP and osteopontin,were expressed constitutively in osteogenic medium after 2 and 4 weeks of culture.Expression of osteocalcin,was induced by osteogenic growth factors at 4 weeks.Induced to chondrogenesis cells were positive of Alcian blue staining under acidic conditions and expression of aggrecan and typeⅡ/Ⅹ collagen genes.Aggrecan and typeⅡcollagen genes were abundant after 2 weeks in chondrogenic medium.TypeⅩ collagen gene was detected at 4 weeks.Conclusion Adipose-derived stem cells can be isolated from rat adipose tissue.Their biological characteristics are similar with mesenchymal stem cells(MSCs),and have the potential to differentiate into osteogenic and chondrogenic lineage.It may be an idea source of ADSCs for tissue engineering.

[Objective]To evaluate the accuracy and influenceing factors of somatosensory evoked potential in spinal cord monitoring during cervical and thoracic spinal surgery and intraoperative nerve root monitoring in lumbar surgery.[Method]The somatosensory evoked potential(SEP) were used during arvical and thoracic spinal surgery and evaluated the accuracy of SEP according to the record of different stages and spinal cord function after surgery.The EMG were used to monitor the nerve root function in lumber operation to estimate whether nerve root being stimulated or tensioned.In addition,affected fators of SEP and EMG during operation were observed.[Result]Of 128 cases of cervical and thoracic surgery,116 cases did not reach the warning standards(amplitude decreasing 50% or diappearing) and showed no postoperative enhancement of symptom of nerve roots injury.12 cases reached the warning standards intraoperatively and the surgeon were warned to take some steps to finish the operations,only in one case incompletely transient paralysis occurred due to the time of amplitude decreasing of intraoperative SEP more than 10 minutes.Effect of other factors such as anaesthesia and low blood pressure did not reach the warning standards.There were 3 artifical negative cases.Only 1 was artifical positive case.of 40 cases of lumbar surgery,12 cases were found myoelectic responses,which warning the surgeon at any time to avoid nerve roots injury,no nerve roots injury were found after operation.[Conclusion]During cervical and thoracic spinal operation,the somatosensory evoked potential can reflect the physiological and pathological conditions of spinal cord after ruling out the interfering factors.Intraoperative spontaneous electromyography can reflect the nerve roots function promptly and accurately and assure the safety of lumbar surgery.

Costimulatory molecule CD_(40) is extensively expressed by immune, hematopoietic, epithelial, and a wide range of tumor cells. As a potential target for novel cancer therapy, CD_(40)/CD_(40L) may mediate tumor regression through both an indirect effect of immune activation and a direct cytotoxic effect on the tumor. Several drug formulations that target the CD_(40)/CD_(40L) pathway have undergone phase I clinical evaluation in advanced-stage cancer patients, and initial findings show objective clinical responses immune modulation function and have not serious toxicity.