Aim: A new derivative LC-MS method was developed for the simultaneous determination of zofenopril and its active metabolite zofenoprilat to investigate the pharmacokinetic characteristics of zofenopril and zofenopri-lat in healthy Chinese volunteers after single and multiple oral doses of zofenopril calcium tablets. Methods: Ten Chinese healthy volunteers were given three single oral doses of 15,30, and 60 mg, respectively, and consecutively the multiple doses of 30 mg. The concentration and pharmacokinetic parameters of both the parent drug and the active metabolite were simultaneously determined by derivative LC-MS method using p-bromophenacyl bromide (p-BPB) as the derivative reagent. Results: After the single oral administrations of 15, 30, and 60 mg of zofeno-pril calcium, there was no significant difference in the t_(1/2) of both zofenopril and zofenoprilat among the three do-ses. The values of AUC_(0-24h) and c_(max) for both zofenopril and zofenoprilat showed the good linearities to the dosage over the dose range from 15 mg to 60 mg. There were no significant differences in AUC_(0-24h) and c_(max) for both com-pounds between female and male volunteers. After multiple oral administration( 30 mg once daily for 6 days ), the average steady state plasma concentration( c_(av)) for zofenopril was (5. 07 ±1. 06) ng/mL with the degree of fluctu-ation (DF) of 14. 26 ± 2. 94. The c_(av) for zofenoprilat was (6. 28 ± 1. 87) ng/mL with the DF of 11. 61 ±4. 68. The accumulation index values for zofenopril and zofenoprilat were 0. 94 ± 0. 31 and 0. 83±0. 13, respec-tively. Conclusion: Both zofenopril and zofenoprilat were demonstrated of linear kinetics after single administra-tion and showed no accumulation after multiple administration of the test zofenopril calcium tablets. There was significant difference in the pharmacokinetic characteristics for zofenopril calcium between healthy Chinese and European volunteers.

BACKGROUND:At present, percutaneous vertebroplasty has been widely used in clinical treatment of osteoporotic vertebral fractures. Considering the limitations of the underlying disease in elderly patients (> 65 years of age) at surgery, the relevant detailed studies have gradualy attracted the attention of clinicians. OBJECTIVE:To compare and analyze the clinical effects of vertebroplasty with bone cement and conventional fracture reduction for elderly osteoporotic thoracolumbar fractures. METHODS:Totaly 24 elderly patients with osteoporotic thoracolumbar fractures were voluntarily divided into bone cement treatment and conservative treatment groups (n=12 per group) and subjected to vertebroplasty with polymethylmethacrylate bone cement and conventional reduction therapy, respectively. RESULTS AND CONCLUSION:Compared with the conservative treatment group, the visual analog scale scores, Oswesty dysfunction index and Cobb angle were significantly reduced in the bone cement treatment group, while the degree of anterior vertebral compression was increased. These results suggest that minimaly invasive spine treatment is conducive to improve the fracture healing and enhance the quality of life in elderly patients with osteoporotic vertebral compression fractures in stable conditions.

Objective To observe colorectal tumor's growth in hyperglycemia mice and its vascular endothelial growth factor (VEGF)'s expression, insulin-like growth factor-1 (IGF-1)'s variation of blood through the experiment, then to ascertain whether type 2 diabetes mellitus (T2DM) danger factors to promote colorectal cancer happen and progress or not. Methods The mouse model of colorectal cancer combined T2DM was established. The volume of tumor was observed. After 5 weeks, all mice were executed and IGF-1 in the blood and the expression of VEGF in the tumor tissue was examined. Results The average tumor volume of colorectal tumor-diabetes group [(1628.5±882) mm3] were larger than that of colorectal tumor group [(1950.2±726) mm3] (P <0.05), and its expression IGF-1 of blood [(105.33±32.32) ng/ml] were higher than that of the control group [(69.83±25.57) ng/ml] and colorectal tumor group [(70.17±25.27) ng/ml] (P <0.05). The expression of VEGF [(70.0±11.5)%] in colorectal tumor-diabetes group were significantly higher than that of colorectal tumor group [(42.9±7.5)%] (P <0.05), too. Conclusion The model of T2DM and transplanted colorectal tumor can be duplicated successfully in ICR mice. Diabetes mellitus may be one reason of promoting colorectal cancer progress. Besides high blood glucose, its mechanism is the high level of IGF-1 which can inhibit apoptosis, promote cell differentiation and hyperplasia, and through inducing VEGF duplicating, heighten its expression, promote the tumor vessel growth, lead to tumor happen and metastasis.

BACKGROUND:Although bone marrow mesenchymal stem cels from multiple myeloma patients present a variety of abnormalities, it is unclear how these abnormal mesenchymal stem cels influence the chemotactic function of myeloma cel lines.
OBJECTIVE:To investigate thein vitro effects of bone marrow mesenchymal stem cels from normal donors versus multiple myeloma patients on the chemotactic capacity of myeloma cel lines.
METHODS:In vitro cultured bone marrow mesenchymal stem cels derived from either normal donors (N-MSCs group) or newly-diagnosed multiple myeloma patients (MN-MSCs group) were directly co-cultured with U266 cels, in the presence or absence of bortezomib; and then harvested U266 cels were assayed for Transwel migration and mRAN expression of chemotaxis-related genes. U266 Transwel migration to conditioned medium derived from either N-MSCs or MN-MSCs was also tested.
RESULTS AND CONCLUSION:After co-cultured with N-MSCs or MN-MSCs, U266 cels harvested from MN-MSCs group showed increased spontaneous Transwel migration and up-regulated CCR1 mRNA level than those from N-MSCs group (P < 0.05), whatever bortezomib was present or not. However, there was no evident difference between U266 cel Transwel migration to conditioned medium derived from either MM-MSCs group or N-MSCs group. Our study implies that there may be some intrinsic aberrance in bone marrow mesenchymal stem cels derived from multiple myeloma patients, which can modulate the chemotactic migration of myeloma cel lines when they directly interact with each other.

Objective To investigate the clinical application of statins for secondary prevention and its efficacy in patients with ischemic stroke.Methods A total of 300 patients with ischemic stroke were divided into statins group (n=91) and control group (n=209) according to whether statins was received or not.Serum lipid parameters,liver and kidney function,carotid artery intimamedia thickness (IMT) and plaque area were compared between the two groups.Results In 209 patients not taking statins,68 cases (32.5％) were not advised by clinic doctor; 55 cases (27.8％)were reluctant to take statins in fear of adverse reactions; 77 cases (36.8％) discontinued stains when serum lipids were normal; 3 cases (1.4％) developed skin allergic reaction and the skin rash that disappeared after stains discontinuance; 3 cases (1.4％) had elevated liver enzyme levels and the enzyme levels were declined to normal after stains discontinuance.The levels of total cholesterol (TC),triglyceride (TG) and low density lipoprotein cholesterol (LDL-C) were significantly lower in statin group than in control group [(4.93±0.45) mmol/L vs.(5.87±0.38) mmol/L,(1.68±0.61)mmol/L vs.(2.01±0.58) mmol/L,(2.49±0.57) mmol/L vs.(3.76±0.44) mmol/L,t=18.60,4.46,20.94,P=0.000,0.007,0.000,respectively].High density lipoprotein (HDL-C) level was significantly higher in stain group than in control group [(1.36±0.31) mmol/L vs.(1.03±0.25)mmol/L,t=9.75,P=0.001].There were no significant differences in liver and kidney function parameters such as alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase,serum total bilirubin,direct bilirubin,indirect bilirubin,glutamyl transferase,blood urea nitrogen and serum creatinine between the two groups (all P＞0.05).The carotid IMT and carotid atherosclerotic plaque area were significantly lower in stain group than in control group [(1.62 ± 0.23) mm vs.(1.74±0.31) mm,(0.57±0.12) cm2 vs.(0.65±0.18) cm2,t=3.32,3.88,P=0.008,0.002,respectively].Conclusions Most patients with ischemic stroke are still not taking statin for secondary prevention.Statins can improve the blood lipid levels and carotid arteriosclerosis status,and no obvious adverse reactions are observed.

Objective To study the clinical features of follicular occlusion triad, and whether it is a hereditary disease. Methods Based on the clinical examination of a case who developed squamous cell carcinoma secondary to follicular occlusion triad, the pedigree of the patient was surveyed and analyzed. Results There were a total of thirteen patients in this pedigree, the age of onset was about 20 years old. The clinical features and laboratory examination of the proband was consistent with follicular occlusion triad. Conclusions Hereditary factor is important in the pathogenesis in follicular occlusion triad,and the disease maybe an autosomal dominant inherited disease.

Objective To discuss the features of nosocomial infection in patients with multiple trauma in intensive care unit and the preventive measures. Method The nosocomial infections occurred in 137 patients with multiple trauma were analyzed including site of infection, pathogenic organisms and bacterial strains. Results The rate of nosocomial infection was 62.8%, mainly the lower respiratory tract infection and wound infection, the G-negative bacteria infection accounted for 67.8%, mostly Escherichia Coli, Pseudomonas aeruginosa and A cinctobacter baumanni I. The G-positive bacteria infection accounted for 32.2%, mainly Staphylococcus aureus and Coagulase negative staphylococcus. The positive detection rates of Klebsiella and pseudomonas aeruginosa were increasing year afer year. Conclusions The incidence of nosocomial infection in patients with multiple trauma is high, suggesting some appropriate preventive measures should be taken to reduce the rate of infection.

To evaluate lesion detection of MRI in knee joint osteoarthritis in patients with symptoms of pain, the correlation between MRI findings and varying degrees of reported pain was assessed. Twenty-eight patients (31 knees) with osteoarthritis were recruited for this study. The degree of knee pain was assessed by VRS scores. The knees were evaluated by plain film radiograph utilizing Kellgren-Lawrence scores. Multiple MR sequences were performed on a 1.5T MR-system, including sagittal and coronal dual fast spin echo (TR/TE 3660/11/120 ms, slice thickness 5 mm), coronal spin echo T1-weighted (TR/TE 360/9 ms, slice thickness 5 mm), sagittal fat saturated 3D-spoiled gradient-recalled echo (TR/TE 50/6 ms; slice thickness 1.5 mm; flip angle 40 degrees ), and 3D steady-state free precession (TR/TE 6/2.2 ms; slice thickness 1.6 mm; flip angle 30 degrees ) pulse sequences for the purpose of detecting abnormities of cartilage, menisci, the anterior cruciate ligaments, bone marrow edema-like lesions, osteophytes, synovitis, and joint effusions. MR findings were compared with the degree of pain using Fisher exact test with P values less than 0.05 indicating a statistically significant difference. The results showed that, of the 31 knees evaluated, mild pain was reported in 11 and severe pain in the remainder. Kellgren-Lawrence scores of all 31 evaluated OA knees were as follows: grade 1 lesions (n=6), grade 2 lesions (n=14), grade 3 lesions (n=8), and grade 4 lesions (n=3). Articular cartilaginous defects were found in 37.1% of knees. Abnormalities of the menisci and anterior cruciate ligaments, bone marrow edema-like lesions, osteophytes, synovitis, and joint effusions were detected in 32.3%, 38.7%, 45.2%, 100%, 15.1% and 67.7% of knees, respectively. Of these variables, only the differences in prevalence of joint effusions were significantly different in the mild and severe pain groups (P=0.004). It is concluded that MRI evaluates the entire joint structure of the osteoarthritic knee, demonstrating abnormalities of the cartilage, menisci, and anterior cruciate ligaments as well as bone marrow edema-like lesions, osteophytes, synovitis, and joint effusions. The difference in pain grading between OA patients reporting mild and severe degrees of pain is related to the presence of joint effusion.

Objective To investigate the mechanism of tumor necrosis factor-α (TNF)-α inhibiting osteo blastdifferentiation of mesenchymal stem cells (BMMSCs) in the pathogenesis of osteoporosis in the mouse model of systemic lupus erythematosus (MRL/lpr). Methods The femurs of MRL / lpr and C3He/HeJ mice were isolated, the bone structure were examined by hematoxylin-eosin (HE) staining. The proteins of TNF-α, NF-κB P50, bone morphogenetic protein -2 (BMP-2) and PSmad1/5/8 were measured by immunohistochemical stain. Bone marrow mesenchymal stem cells (BMMSCs) were isolated. After BMMSCs grew on the cover slips, the proteins on top of it were evaluated by immunohistochemistry stain. Moreover, the alkaline phosphatase (ALP) staining was employed for the measurement of the early osteogenic differentiation. BMMSCs together with hydroxyapatite were embedded subcutaneously in the nude mice and eight weeks later, the ectopic bone formation was evaluated. The recombinant human tumor necrosis factor receptor type Ⅱantibody fusion protein (etanercept) or normal saline was subcutaneous injected to the mice with lupus. After four weeks, the expression of these proteins was observed and the ectopic bone formation was investigated. Image-Pro plus 6.0 software was employed for imagine analysis, and Studentˊs t-test was used to test the differences between 2 independent groups. Results MRL/lpr mice showed decreased volume of cortex and the percentage of cortex to the volume of bone of MRL/lpr mice was significantly lower compared to control groups and with C3He/HeJ mice (13.96±0.25 vs 23.61±0.71, n=3, P<0.01). The protein levels of both TNF-αand NF-κB P50 on the femur of MRL/lprl mice were higher than those of the control group (0.643±0.051 vs 0.405±0.022, 0.917±0.023 vs 0.650±0.032, n=3, P<0.01). The expressions of BMP-2 on the femur of MRL/lpr mice were lower than those of the C3He/HeJ mice (0.52 ±0.03 vs 0.72 ±0.03, n=3, P<0.01). There was no difference in the expression of PSmad1/5/8 on the femur between the two groups by immunohistochemistry detection (1.264 ±0.021 vs 1.301± 0.044, n=3, P>0.05). The expressions of TNF-α and NF-κB P50 in BMMSCs of MRL/lprl mice were higher than those of the C3He/HeJ (0.184±0.021 vs 0.136±0.013, 0.132±0.021 vs 0.097± 0.014, n=3, P<0.01), while BMP-2 and PSmad were lower than those of the control group (0.128±0.013 vs 0.216±0.221, 0.115±0.023 vs 0.196±0.034, n=3, P<0.01). After 7 days of BMP-2 stimulation, the activities of ALP of BMMSCs from MRL/lprl mice were reduced detected by ALP staining and the osteoblast differentiation of these cells were decreased than BMMSCs from the control mice by HE and Masson staining. The percentage of the cortex to the volume of bone of the etanercept injection MRL/lpr mice was higher than that of the control group (21.8±1.0 vs 14.3 ±0.6, n=3, P<0.01). Moreover, the proteins of TNF-α and NF-κB P50 on the femurs of such injected mice were lower than those of the control group (0.540±0.024 vs 0.682±0.031, 0.857±0.023 vs 1.098±0.044, n=3, P<0.05), while the expressions of BMP-2 were higher than the control group (0.99±0.04 vs 0.85±0.04, n=3, P<0.05). There was no difference in the PSmad1/5/8 expression on the bone of the two group of lupus mice (0.88 ±0.08 vs 0.84 ±0.04, n=3, P>0.05). The ectopic bone formation of BMMSCs of the etanercept injected MRL/lpr mice was higher than that of the normal saline injected mice, however, it was lower than that of the C3He/HeJ mice. Conclusion TNF-α inhibits osteoblast differentiation of mesenchymal stem cells by depressing Smad signaling which may contribute to the osteoporosis of the lupus mice.

Objective:To study the neuro-protective effects of Shenfu injection on Nrf 2 signaling pathway affected by cerebral ischemia reperfusion.Methods: A total of 68 adult male Sprague-Dawley rats were randomly divided into sham group , cerebral ischemia-reperfusion group,and(8 mg/kg)Shenfu injection treatment group.Shenfu injection was injected intraperitoneally in the rats after MCAO.Neurologic deficit was evaluated after 24 hours of reperfusion.All the rats were sacrificed after 24 h of ischemia-reoerfusion for biochemical analysis or Nissl staining.Results:Shenfu injection treatment significantly increased the expression of Nrf 2,HO-1 and NQO-1(P<0.05).Furthermore,Shenfu injection treatment significantly reduced the expression of cleaved -caspase-3 and attenuated neurological deficits after cerebral ischemia reperfusion ( P<0.05 ).Lastly, Shenfu injection could evidently alleviate the severity of neuronal degeneration ( P<0.05 ).Conclusion:Shenfu injection could confer neuroprotection after cerebral ischemia reperfusion through modulating the Nrf2 signaling pathway.