Animals ; Benzofurans ; pharmacology ; therapeutic use ; Bone Marrow Cells ; cytology ; Cell Differentiation ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Humans ; Mesenchymal Stem Cell Transplantation ; methods ; Mesenchymal Stromal Cells ; cytology ; Myocardial Infarction ; drug therapy ; therapy ; Myocytes, Cardiac ; cytology ; Phytotherapy ; Salvia miltiorrhiza ; chemistry

Objective To establish a high performance liquid chroma-tography-tandam mass spectrometry ( HPLC-MS/MS) method for de-termining the concentration of sunitinib and N -desethyl sunitinib (SU12662) in human plasma.Methods Sunitinib, SU12662 and in-ternal standard sunitinib -D10 were extracted from plasma with one -step protein precipitation and the stereoselective analysis of sunitinib and SU12662 was achieved on an Agilent ZORBAX Extend C18 (2.1 mm ×75 mm ×3.5 μm) with gradient elution by a mobile phase consisting of wa-ter containing 0.1%formic acid and 95%acetonitrile.Electrospray ioni-zation source was applied, and multiple reaction monitoring mode was operated in the positive mode with the monitor ions at m/z 399.3→326.1 for sunitinib, m/z 371.3→283.1 for SU12662 and 409.3→326.2 for sunitinib-D10.Results The calibration curve for plasma sunitinib was linear in the range of 0.5-200 ng? mL-1 ( r=0.998 7) , the lower limi-tation of quantification was 0.5 ng? mL-1 , while the accuracy was ranged from 0.57% to 2.87%, the average recovery rate was ranged from 92.75%to 98.62%,and intra-and inter-day RSD were ranged from 0.91%to 1.92%and 5.40%to 7.87%, respectively.The calibration curve for plasma SU12662 was linear in the range of 0.25 -100 ng? mL-1 ( r =0.999 9 ) , while the accuracy was ranged from -2.08% to 2.80%, the average recovery rate was ranged from 96.23%to 101.12%, and intra-and inter-day RSD were ranged from 0.46%to 2.46%and 5.84%to 9.75%, respectively, the lower limitation of quantification was 0.25 ng? mL-1 .Conclusion The HPLC-MS/MS method was accurate, sensitive, specific, and could be used in the determination of sunitinib in plasma and the clinical study of its pharmacokinetics.

BACKGROUNDValproic acid (VPA) improves early survival and organ function in a highly lethal poly-trauma and hemorrhagic shock model or other severe insults. We assessed whether VPA could improve organ function in a rat model of septic shock and illustrated the possible mechanisms.

METHODSForty Sprague-Dawley rats were randomly assigned to four groups (n = 10): control group, VPA group, LPS group, and LPS + VPA group. Lipopolysaccharide (LPS) (10 mg/kg) was injected intravenously to replicate the experimental model of septic shock. Rats were treated with VPA (300 mg/kg, i.v.) or saline. Six hours after LPS injection, blood was sampled for gas analysis, measurement of serum alanine aminotransferase, aspartate aminotransferase, urine nitrogen, creatinine and tumor necrosis factor-alpha. Lung, liver and kidney were collected for histopathological assessment. In addition, myeloperoxidase activity and tumor necrosis factor-a in pulmonary tissue were measured. Acetylation of histone H3 in lung was also evaluated by Western blotting.

RESULTSLPS resulted in a significant decrease in PaO2, which was increased by VPA administration followed LPS injection. In addition, LPS also induced an increase in the serum levels of alanine aminotransferase, aspartate aminotransferase, urine nitrogen, creatinine, and tumor necrosis factor-alpha. However, these increases were attenuated in the LPS + VPA group. The lungs, liver and kidneys from the LPS group were significantly damaged compared with the control group. However, the damage was attenuated in the LPS + VPA group. Myeloperoxidase activity and tumor necrosis factor-alpha levels in pulmonary tissue increased significantly in the LPS group compared with the control group. These increases were significantly inhibited in the LPS + VPA group. Acetylation of histone H3 in lung tissue in the LPS group was inhibited compared with the control. However, the level of acetylation of histone H3 in the LPS + VPA group was markedly elevated in contrast to the LPS group.

CONCLUSIONSTreatment with VPA can attenuate multiple organ damage caused by LPS induced septic shock. Our data also suggest that the beneficial effects are in part due to the decrease in inflammatory cytokines and restoration of normal acetylation homeostasis.

Acute Kidney Injury ; drug therapy ; metabolism ; Animals ; Blotting, Western ; Chemical and Drug Induced Liver Injury ; drug therapy ; metabolism ; Lung Injury ; drug therapy ; metabolism ; Male ; Multiple Organ Failure ; drug therapy ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Shock, Septic ; drug therapy ; metabolism ; Valproic Acid ; therapeutic use

Objective:To explore the value of echocardiography for diagnosing infectious endocarditis (IE).Methods:A total of 487 patients with cardiovascular implantable electronic devices (CIED) infection treated in our hospital from 2013-01 to 2015-06 were enrolled.Based on symptoms,blood culture and echocardiography,9 patients with suspected IE were further examined by 18F-FDG PET-CT to confirm their diagnosis and classification.Definitive therapy was conducted and the patients were followed-up for 1 year to confirm the diagnostic accuracy of echocardiography on CIED induced IE.Results:3 patients were preliminarily diagnosed for bacteremia since no vegetation was found by echocardiography,while IE was finally diagnosed by PET-CT.2 patients were preliminarily diagnosed for IE by echocardiography presented valvular vegetation,while PET-CT showed no evidence of vegetation;then one of them was diagnosed as bacteremia by positive blood culture and another was diagnosed as non-infection.4 patients were preliminarily diagnosed for IE by echocardiography indicated existing vegetation after CIED lead extraction,while PET-CT demonstrated no infection sign in heart chamber and the finally diagnosed was as "non-infectious fibrous residual tissue".According to final diagnosis,definitive therapies were performed to specific patients with at least 1 year follow-up study,no one had new and recurrent infection.Conclusion:Echocardiography had deficiency for diagnosing vegetation in heart chamber especially in suspicious IE patients after CIED lead extraction.It is necessary to make accurate diagnosis with other method for guiding appropriate therapy.

OBJECTIVETo construct replication selective adenovirus AdhepE1 targeting human melanoma and observe its specific killing of human melanoma cells in vitro.

METHODSAdenovirus E1 region, the murine tyrosinase promoter and enhancer DNA sequences were acquired respectively by PCR cloning. The shuttle plasmid of replication-selective adenovirus targeting human melanoma was constructed by DNA recombination. Replication-selective adenovirus AdhepE1 was generated by homologous recombination. The human melanoma cell line SK-Mel-1 and hepatocellular carcinoma cell line HepG2 were attacked separately by lower dose of AdhepE1. Change of cell morphology was observed and the surviving cells were calculated. The expression of E1A was assayed by RT-PCR to verify the specific-replication of AdhepE1.

RESULTSReplication selective adenovirus AdhepE1 targeting human melanoma was acquired by PCR. Human melanoma cell line SK-Mel-1 was sensitive to oncolytic killing of AdhepE1 whereas HepG2 was little responsive. The results of RT-PCR suggested that AdhepE1 replicated specifically in human melanoma cells.

CONCLUSIONAdhepE1 can selectively kill human melanoma cells.

Adenoviridae ; genetics ; Animals ; Cell Line, Tumor ; Genetic Therapy ; Humans ; Liver Neoplasms ; therapy ; Melanoma ; therapy ; virology ; Mice ; Reverse Transcriptase Polymerase Chain Reaction ; Virus Replication

OBJECTIVETo study the etiology and clinical significance of axial symptoms after posterior operative procedures for ossification of the posterior longitudinal ligament (OPLL).

METHODSFrom February 2005 to February 2010, 76 patients with OPLL treated were retrospectively experienced. There were 34 male and 42 female with average of 52.1 years (range from 37 to 74 years), the average duration of the disease was 32.1 months (range from 11 to 56 months). Nineteen patients underwent traditional laminectomy in group A, 33 patients received open-door laminoplasty in group B and 24 patients underwent lateral mass screw fixation in group C. All patients underwent X-ray examination pre- and post operative, computed tomography were used for diagnosis of OPLL, the recovery rate was calculated using pre- and postoperative Japanese Orthopedic Association (JOA) scores for each patient. Pre- and postoperative cervical curvature index and axial symptoms were measured and compared. χ(2) test and SNK test were used as statistical methods.

RESULTSAll patients were followed up for 14 - 35 months, average (21 ± 5) months. Loss of cervical curvature index was 4.2% ± 1.7% in group A, 2.9% ± 2.2% in group B and 2.3% ± 1.9% in group C. The difference was significant in loss of cervical curvature indice between group A and B (q = 2.94, P < 0.01), group A and C (q = 4.23, P < 0.01). The average JOA recovery rate was 58.3% for group A, 64.3% for group B and 66.7% for group C. There was no significant difference in JOA recovery rate among the three groups (P > 0.05). The rate of early evident axial symptoms was 7/19 in group A, 30.3% in group B and 33.3% in group C and the difference was not statistically significant (P > 0.05). The incidence of late evident axial symptoms was 5/19 in group A, 12.1% in group B and 8.3% in group C, the difference was not significant between group B and C (χ(2) = 13.762, P < 0.01), but of statistical difference between group A and B(χ(2) = 6.368, P < 0.01), group A and C (χ(2) = 11.481, P < 0.01). No kyphotic deformity in the group A, no "Close Door" phenomenon in group B and no internal failure in group C.

CONCLUSIONThe incidence of early axial symptoms are of no significant difference among the three groups, but late axial symptoms are higher in the laminectomy than other groups, which may be associated with loss of cervical lordosis.

Adult ; Decompression, Surgical ; adverse effects ; methods ; Female ; Follow-Up Studies ; Humans ; Laminectomy ; adverse effects ; methods ; Male ; Middle Aged ; Ossification of Posterior Longitudinal Ligament ; surgery ; Postoperative Complications ; Retrospective Studies

OBJECTIVESTo investigate the radiological change of bilateral paravertebral muscles in degenerative lumbar scoliosis (DLS) and analyze its clinical significance.

METHODSAs a retrospective study, 66 patients with DLS and 66 patients with lumbar spinal stenosis were retrospectively enrolled from April 2004 to August 2011 as scoliosis group and lumbar spinal stenosis group, meanwhile 66 health persons with no lumbar spinal stenosis were selected as control group. No significant differences were found in the gender, age and body mass index among the three groups. The cross-sectional area (CSA) and percentage of fat infiltration area (FIA) of the bilateral paravertebral muscles at the L(1)-S(1) levels were measured using T2-weighted axial MRI and Image J software. The measured data were analyzed with a paired t-test.

RESULTSIn the DLS with bilateral symptom group, the mean percentage of FIA of the multifidus muscle on the convex side were 18% ± 4%, 21% ± 4%, 27% ± 4%, 34% ± 6%, 42% ± 10% and on the concave side were 25% ± 8%, 30% ± 7%, 35% ± 7%, 40% ± 10%, 44% ± 8% at L(1-2), L(2-3), L(3-4), L(4-5) and L(5)-S(1) levels, which showed significant differences between the convex side and the concave side (t = 7.95, 9.30, 5.35, 2.78, 2.38, P < 0.05); the mean percentage of FIA of the longissimus muscle on the convex side were 25% ± 9%, 28% ± 8% and on the concave side were 27% ± 9%, 31% ± 9% at L(3-4), L(4-5) levels, which showed significant differences between the convex side and the concave side (t = 2.52, 3.48, P < 0.05). There were no significant differences in the CSA of both muscles between the concave and convex sides (P > 0.05). In the DLS with unilateral symptom group, the mean percentage of FIA of the multifidus muscle on the convex side were 18% ± 5%, 23% ± 5%, 29% ± 5%, 34% ± 6%, 42% ± 9% and on the concave side were 23% ± 6%, 30% ± 7%, 36% ± 7%, 41% ± 10%, 45% ± 8% at L(1-2), L(2-3), L(3-4), L(4-5) and L(5)-S(1) levels, which showed significant differences between the convex side and the concave side (t = 6.67, 7.96, 6.43, 3.86, 2.15, P < 0.05). There were on significant differences in the CSA of both muscles, and in the percentage of FIA of the longissimus between the concave and convex sides (P > 0.05).

CONCLUSIONSThere exist asymmetric degeneration in paravertebral muscle in DLS, which have potential clinical importance on the evaluation of curve progression, and muscle degeneration is more often seen in the concave side. Spinal deformity and radiculopathy may contribute to the paravertebral muscle degeneration.

Aged ; Case-Control Studies ; Female ; Humans ; Lumbar Vertebrae ; diagnostic imaging ; pathology ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Muscle, Skeletal ; diagnostic imaging ; pathology ; Muscular Atrophy ; pathology ; Radiography ; Retrospective Studies ; Scoliosis ; diagnostic imaging ; pathology

OBJECTIVETo determine the spatio-temporal expression of p70S6k activation in hippocampus in mesial temporal lobe epilepsy.

METHODSTemporal lobe epilepsy model was established by stereotaxically unilateral and intrahippocampal injection of kainite acid (KA) in adult male C57BL/6 mice. Latent and chronic epileptogenesis were represented by mice 5 days after KA injection (n = 5) and mice 5 weeks after KA injection (n = 8), respectively. Control mice (n = 5) were injected with saline. Immunohistochemical assays were performed on brain sections of the mice.

RESULTSHippocampus both ipsilateral and contralateral to the KA injection displayed significantly up-regulated pS6 immunoreactivity in dispersed granule cells in 5-day and 5-week model mice.

CONCLUSIONThe activation of p70S6k is mainly located in the dentate gyrus in KA-induced mouse model of temporal lobe epilepsy, indicating that the activation may be related with the disperse degree and hypertrophy of granule cells.

Animals ; Epilepsy, Temporal Lobe ; enzymology ; Hippocampus ; enzymology ; Immunohistochemistry ; Male ; Mice ; Mice, Inbred C57BL ; Phosphorylation ; Ribosomal Protein S6 Kinases, 70-kDa ; analysis ; metabolism

BACKGROUNDDegenerative lumbar scoliosis is common in older patients. Decreased bone density and the degeneration of intervertebral discs are considered to be correlated with degenerative lumbar scoliosis. A means of quantifying the relative signal intensity for degenerative disc disease has not been previously discussed. The purpose of this study was to compare bone mineral density and intervertebral disc degeneration between degenerative lumbar scoliosis and lumbar spinal stenosis patients in a nine-year retrospective study.

METHODSFrom January 2001 to August 2010, 96 patients with degenerative lumbar scoliosis were retrospectively enrolled and 96 patients with lumbar spinal stenosis were selected as controls. Cobb angle, height of the apical disc and the contiguous disc superiorly and inferiorly on convex and concave sides, the height of the convex and concave side of the apical and the contiguous vertebral body superiorly and inferiorly were measured in the scoliosis group. The height of L2/L3, L3/L4, L4/L5 discs and the height of L2/L4 vertebral body was measured in the control group. The grade of intervertebral disc degeneration was evaluated using T2WI sagittal images in both groups. The bone density of lumbar vertebrae was measured with dual-energy X-ray.

RESULTSIn scoliosis group, the intervertebral disc height on the convex side was greater than the height on the concave side (P < 0.001). The vertebral body height on the convex side was greater than the height on the concave side (P = 0.016). There was a significant difference between the scoliosis group and the control group (P = 0.003), and between T-value and the rate of osteoporosis between the two groups (both P < 0.001).

RESULTSwere verified using multiple linear regression analysis.

CONCLUSIONSDegenerative lumbar scoliosis is accompanied by height asymmetry between the intervertebral disc and vertebral body regarding the convex and concave surfaces. There is a positive correlation between the angle of scoliosis and the disc index, the degree of degeneration of the intervertebral disc, and a negative correlation between the angle of scoliosis and bone density.

Aged ; Bone Density ; physiology ; Female ; Humans ; Intervertebral Disc ; pathology ; Intervertebral Disc Degeneration ; pathology ; physiopathology ; Linear Models ; Male ; Middle Aged ; Retrospective Studies ; Scoliosis ; pathology ; Spinal Stenosis ; pathology

BACKGROUNDBryan cervical disc arthroplasty can be used to restore and maintain the mobility and function of the involved cervical spinal segments. The efficiency of posterior longitudinal ligament (PLL) resection in anterior cervical decompression and fusion has been demonstrated. However, no clinical reports have compared PLL removal with preservation in Bryan cervical disc arthroplasty. This study aimed to assess the role of removal of PLL in Bryan cervical disc arthroplasty at an 18-month follow-up.

METHODSWe performed a prospective investigation of clinical and radiological outcomes in patients after Bryan cervical disc arthroplasty. Sixty patients who underwent Bryan cervical disc arthroplasty were included. The PLL was removed in 35 patients (investigational group) and preserved in 25 patients (control group). All of the patients were followed up for more than 18 months. Clinical (Japanese Orthopedic Association score and Visual Analogue Scale pain score) and radiological (functional spinal unit (FSU) angle, range of movement (ROM), and diameter of the spinal cord) parameters were compared between the two groups before and after surgery (18 months).

RESULTSClinical outcomes in the investigational group were significantly superior to those in the control group. There were no significant differences in the FSU angle and ROM (P = 0.41 and 0.16, respectively) between the two groups. However, the increase in diameter of the spinal cord in the investigational group was significantly greater than that in the control group (P < 0.01).

CONCLUSIONSRemoval of the PLL can improve the clinical outcomes of Bryan cervical disc arthroplasty. This procedure does not have a large effect on imbalance and motion of the cervical spine.

Adult ; Arthroplasty ; methods ; Cervical Vertebrae ; surgery ; Female ; Humans ; Longitudinal Ligaments ; surgery ; Male ; Middle Aged ; Prospective Studies