Objective To investigate the expressions of receptor for advanced glycation endproducts (RAGE) and nuclear factor κB(NF-κB) in brain hippocampus of rat with chronic fluorosis,and to reveal the mechanism of brain damage resulted from chronic fluorosis.Methods Sixty clean grade SD rats were randomly divided to three groups(20 rats in each group,10 female and 10 male) fed with different contents of fluoride,control group with normal tap-water(＜ 0.5 mg/L fluoride),small dosage of fluoride exposure group(10 mg/L fluoride in tap-water) and large dosage of fluoride exposure group(50 mg/L fluoride) for six months.Then the rats were killed by femoral artery bleeding and hippocampus was removed.Protein and mRNA levels of RAGE and NF-κB in the hippocampus were determined by Western blotting and quantitative real time PCR,respectively.Results As compared to the control groups[(100.00 ± 2.60)％,(100.00 ± 7.80)％],the expressions of RAGE and NF-κB at protein level in the hippocampus were significantly increased in the small dosage of fluoride exposure groups [(205.00 ± 15.30)％,(156.00 ± 12.20)％] and the large dosage of fluoride exposure groups[(232.00 ± 10.90)％,(162.00 ± 9.80)％,all P ＜ 0.05]; for the mRNA level of RAGE and NF-κB,the expressions were higher in the small dosage of fluoride exposure groups(1.27 ± 0.09,0.83 ± 0.15) and the large dosage of fluoride exposure groups (2.60 ± 0.19,1.27 ± 0.19) than those of the control groups(0.66 ± 0.18,0.32 ± 0.08,all P＜ 0.05).Conclusions The increased expressions of RAGE and NF-κB in the hippocampus of rat brain are caused by chronic fluorosis,and these changes may be associated with the mechanism of nerve injury.

Objective Aim of the study is to investigate the expression of syndecan-4 and nuclear factor κB(NF-κB) in the kidney of rat with chronic fluorosis,and to reveal the mechanism of kidney damage resulted from the toxicity of excessive amount of fluoride.Methods According to body mass and sex,sixty SD rats were randomly divided to three groups according to body mass and fed with different contents of fluoride:control group with normal tap-water(＜ 0.5 mg/L fluoride),small dosage of fluoride exposure group (adding 10 mg/L fluoride in tap-water) and large dosage of fluoride exposure group (50 mg/L fluoride) for six months.The protein level of syndecan-4 and NF-κB in the kidney was detected by Western blotting and syndecan-4 mRNA level by quantitative real time PCR.Results As compared to the control group[(100.0 + 8.1)％],the expression of syndecan-4 at protein level in the kidney of rat was significantly increased in the small dosage of fluoride exposure group [(198.5 + 5.6)％,P ＜ 0.05] and large dosage of fluoride exposure group [(209.2 + 13.0)％,P ＜ 0.05]; the protein levels of NF-κB in the small dosage of fluoride exposure group[(284.4 + 11.1)％,P ＜ 0.05] and in the large dosage of fluoride exposure group[(343.2 + 2.9)％,P ＜ 0.05] were significantly increased than that of the control group[(100.0 ± 10.7)％].The mRNA levels of syndecan-4 in the kidney in the small dosage of fluoride exposure group and large dosage of fluoride exposure group(0.431 + 0.058 and 0.453 ± 0.065,both P ＜ 0.05,respectively) were significantly increased than that of the control(0.128 + 0.026).Conclusions The increased expression of NF-κB in the kidney is induced by increased expression of syndecan-4,which may be involved in kidney damage of chronic fluorosis.

Objective To explore the blood drug concentration monitoring of sustained-release valproate(DK)in children with epilepsy,focusing on the selection of sampling time and evaluation of the results.Methods Two hundred and seventy-one children taking DK and 155 children taking sodium valproate syrup(VPA Syr)were involved and their serum were taken when achieved steady state to determine the valproic acid level using fluorescence polarization immunoassay.They were divided into 4 groups,which were DK taken once daily group(DK qd group,126 children),DK taken once daily at night and sampled on morning group(DK qn group,26 children),DK taken every 12 h group(DK q12 h group,119 children),VPA Syr q12 h group(155 children).Determine the proportion of the blood drug concentration of each group below,ithin and above the therapeutic range for valproate(50-100 mg/L)were determined.The data were analyzed by t test.Results The Cmin of DK qd group were(73.09?19.91)mg/L,significantly lower from the serum concentration of DK qn and sampled on morning group [(94.94?25.44)mg/L](P0.05).Conclusions DK qn should sampled at night before the night dose.The Cmin of DK q12 h was higher according to the therapeutic range,it's favorable range still needs clinical practice.

Objective To assess the effect of two-dimensional speckle tracking imaging (STI) on prognosis of patients with acute infarcted myocardial(AMI).Methods Eighty patients with AMI and 30 healthy subjects were selected as our subjects.Among the AMI patients,there was 30 cases were emergency percutaneous coronary intervention (PCI),25 cases were selective PCI group and 25 cases with conservative.All were performed a 4-6 months following up after discharge from hospital.Left ventricular ejection fraction(LVEF) was measured by Simpson's.Rotation were measured in the left ventricular basal and apical short-axis views using STI.LV Peak twist (Ptw),apical Peak rotation (PAR),the basal Peak rotation (PBR),twist at aortic valve closure(AVC tw),twist at mitral valve opening(MVO tw),untwisting rate (Untw R),and half time of untwisting (HTU) were calculated.And the correlation between Ptw and LVEF was analyzed.Results Compared with the control group,the value of Ptw,PAR,AVC tw and MVO tw were significantly decreased in myocardial infarction group(F =22.481,12.899,18.923 ;P ＜ 0.05).Ptw,PAR in emergency PCI group at following up periods were (18.61 ± 8.08) ° and (12.16 ± 6.98) °,higher than that in hospital periods ((13.76 ± 6.31) °,(7.03 ±5.76)°).Ptw,PAR in selecting PCI group were (19.5 ±7.73)° and (13.4 ±7.02)°,higher than that in hospital periods((15.25 ± 6.83) °,(9.69 ±.6.72) ° ; t =-2.607,-3.104,-2.079,-1.955 ; P ＜ 0.05).Significant correlation was found between Ptw and LVEF (r =0.527,P ＜ 0.05).Conclusion Left ventricular twist can be measured using STI.LV rotation can be the quantitative index to evaluate the systolic function of LV.STI can be the new method to guide clinic diagnosis and therapy.

Discogenic low back pain is the common type of chronic low back pain. However,its mechanism has not been completely clarified. Considerable evidence shows that neurotrophins play an important role in discogenic low back pain. The paper summarizes the mechanism of neurotrophins on discogenic low back pain according to the pain transfer pathway of neurotrophins in intervertebral disc, dorsal horn ganglia and spinal trigeminal nucleus. Changing the pain transmission by regulating neurotrophins and its receptor will provide a new way for the treatment of discogenic low back pain.
Humans ; Intervertebral Disc ; metabolism ; pathology ; Low Back Pain ; metabolism ; pathology ; Nerve Growth Factors ; metabolism ; Posterior Horn Cells ; pathology ; Trigeminal Nucleus, Spinal ; pathology

Objective To investigate skin manifestations and comorbidities of chronic arsenicosis due to conta?minated drinking water, and to explore their possible risk factors. Methods Data about demographic characteristics, skin manifestations and comorbidities were collected from 95 patients with chronic arsenicosis due to contaminated drinking water in Inner Mongolia, and retrospectively analyzed. A logistic regression model was established to analyze associations of skin manifestations and comorbidities with patients′ gender, age, age at onset of drinking of arsenic?contaminated water, arsenic concentrations in water and duration of arsenic exposure. Results Among the 95 patients, 77 had hyperpigmentation, 75 hypopigmentation, 93 palmoplantar keratoderma, 27 skin cancer, and 8 multiple skin cancer. Five patients were complicated by tuberculosis, 15 by hypertension, 2 by rheumatoid arthritis, 4 by cerebral infarction, 7 by coronary heart diseases, 3 by internal malignancy, 6 by hepatic cirrhosis and 2 by anemia. Logistic regression analysis revealed a significant correlation between hyperpigmentation and arsenic concentrations in water(OR=0.32, 95%CI=0.10-0.98;ORadjusted=0.27, 95%CI=0.08-0.90), between occurrence of hepatic cirrhosis and arsenic concentrations in water (OR=24.67, 95%CI=2.69-226.57;ORadjusted=22.51, 95%CI=2.38-213.11), and between occurrence of coronary heart diseases and duration of arsenic exposure(OR=6.41, 95%CI=1.09-37.88;ORadjusted=8.55, 95%CI=1.21-60.41). Conclusions There is a high incidence of aberrant pigment metabolism, palmoplantar keratoderma and skin cancer in patients with chronic arsenicosis due to contaminated drinking water. Different arsenic concentrations in water and duration of arsenic exposure seem to have different influences on the human body.

Objective To observe the effect of low dosage of uhrashortwave(USW) on infarction volume, B cell lymphocytoma-xl (Bcl-xl) and tumor necrosis factor alpha (TNF-?) after cerebral ischemia-reperfusion in rats and discuss its acting mechanisms. Methods Focal ischemia-reperfusion model was established in 25 rats by re- versible right middle cerebral artery occlusion with filament. The right side cerebral ischemia was lasted for 2 hours and then followed with 24 hours of reperfusion. The content of neurological deficits were evaluated by the Zea-Longa 5-degree scoring system to select rats. After surgery, the rats were divided into 3 groups: blank control group, control group and USW treatment group. The brain of all rats was taken at 24 hours after reperfusion. The cerebral infarction volume, the expression of Bcl-xl and TNF-?were measured and analyzed. Results Twenty-five rats were used in the analysis of results. When compared with the control group, the infarction volume and rate in total cerebral volume of USW group significantly decreased (t = 2.54, 2.33, P

Objective To explore the effect and safety of transcranial approach for spheno-orhital meningioma. Design Retro- spective case series. Participants Thirty-two patients being operated with transcranial approach. Twenty-four cases were meningothelial meningiomas, 3 cases were fibrous meningiomas, 1 case was psammomatous meningioma, 2 cases were atypital meningiomas, 2 case were malignant meningiomas. Methods All patients underwent frontal-temporal craniotomy, the involved sphenoid wing bone and peri- orbit were removed to prevent recurrence. The superior orbital fissure and optic canal were decompressed, the dural and periorbital de- feet were repaired by autogenous temporal fascia or artificial dura. Main Outcome Measures Preoperative and postoperative exoph- thalmus and eyeball movement, the extent of tumor resection, the ratio of recurrence. Results The extent of tumor resection: 8 cases were Simpson gradeⅡ, 20 cases Simpson gradeⅢ, 4 cases Simpson grade IV. After surgery, proptosis were improved in all patients, ophthalmoplegia was found in 6 eases. There was no operation-related death or other significant complication. Tumor recurred in 6 cas- es. Conclusions Adequate exposure of the tumor and bony decompression of the cranial nerves can result from transcranial approach, all the involved bone should be removed in order to prevent recurrence. This approach is relatively safe and the ptoptosis are improved significantly. Complete surgical resection is difficult because of the involvement of the orbital apex, superior orbital fissure and cav- ernous sinus.

Peptide cyclization, a pivotal approach to modifying linear precursors of proteins and pepticles, has been used to enhance their biological activities and serum stabilities. Recently, sortase A (SrtA) from Staphyloccus aureus becomes a promising new technology for efficiently incorporating site specific modifications into proteins, conjugating the cell surface and cyclizing the linear peptides. In this study, we constructed two recombinant expression systems, one with chitin binding domain and the other with six-histidine tag and chitin binding domain on the N-terminal of SrtA, separately. The results of enzymatic kinetics indicate that the two recombinant tags do not impair the transpeptidase activity of SrtA compared with the standard reaction reported under the same reaction condition. The two synthesized peptides with N-ternimal three glycines and C-terminal penta-amino acid motif, LPETG, were cyclized using immobilized and recycled SrtA. The SrtA-based cyclization promises to represent a simple method for easy and efficient enzymatic synthesis of large cyclic peptides.
Aminoacyltransferases ; metabolism ; Bacterial Proteins ; metabolism ; Cyclization ; Cysteine Endopeptidases ; metabolism ; Enzymes, Immobilized ; metabolism ; Kinetics ; Peptides ; metabolism ; Peptides, Cyclic ; biosynthesis ; Staphylococcus aureus ; enzymology

OBJECTIVETo evaluate the clinical efficacy and safety of phosphodiesterase 5 (PDE-5) inhibitors for erectile dysfunction (ED) in patients with diabetes mellitus and provide some evidence for the clinical treatment of the disease.

METHODSWe searched MedMed, EMbase, Cochrane Library, CNKI, Wan Fang Data, VIP and ZADL for randomized controlled trials on PDE-5 inhibitors for ED in diabetic men and evaluated the methodology of the included trials with the Jadad scale. We used the erectile function domain in the IIEF (IIEF-EF), IIEF questions (IIEF-Q) 3 and 4, SEP-2 and -3, and Global Assessment Questions (GAQ) as the main evaluation indexes and employed the Review Manager 5. 1. 0 software for meta analysis.

RESULTSA total of 13 studies were included, which were all high quality trials with Jadad score > 3. The IIEF-EF scores in 10 of the included studies were subjected to meta analysis using the random-effect model (REM), with a weighted mean difference (WMD) of 5.64 (95% CI 4.41 - 6.83, P < 0.001). The fixed-effect model (FEM) analysis of the IIEF-Q scores in 6 of the studies showed the WMD to be 0.96 (95% CI 0.83 -1.08, P < 0.001) for IIEF-Q3 and 1.11 (95% CI 0.98 - 1.25, P < 0.001) for IIEF-Q4. FEM analysis of the SEP-2 scores showed WMD = 17.67 (95% CI 12. 38 - 22. 97, P < 0.001) in 2 of the studies, and that of the SEP-3 scores WMD = 23.64 (95% CI 17. 49 - 29.79, P < 0.001) in 5 of the studies. The GAQ scores in 11 of the studies were subjected to REM analysis, with OR = 6. 20 and 95% CI 3.65 - 10.52 (P < 0.001). REM analysis was performed on the adverse reactions in 11 of the studies, with OR = 7.43 and 95% CI 4.11 - 13.44 (P < 0.001).

CONCLUSIONPDE-5 inhibitors can effectively and safely improve erectile function in patients with diabetes mellitus.