Objective: To develop and optimize a self-microemulsifying drug delivery system (SMEDDS) formula for improving the dissolution of atorvastatin calcium.Methods: Solubility and pseudo-ternary phase diagram were used to select the suitable type and amount range of oil phase, surfactant and co-surfactant.D-optimal mixture design was used to optimize the formula of atorvastatin calcium SMEDDS.The morphology, particle size distribution and zeta potential of the microemulsion were determined by a dilution method.The in vitro drug release profiles of the marketed atorvastatin calcium tablets and the self-made SMEDDS were compared.Results: The formula of atorvastatin calcium SMEDDS was as follows: Capmul MCM as the oil phase, Labrasol as the surfactant and Transcutol P as the co-surfactant with the optimal weight ratio of 13.0∶43.5∶43.5.The self-made SMEDDS was a clear and transparent microemulsion solution with homogeneous small spheres as seen under a transmission electron microscope.The particle size, PdI and zeta potential of the self-made SMEDDS was (34.2±13.6) nm, (0.169±0.04) and (-21.1±1.3) mV, respectively.The in vitro release profile indicated that the accumulated release of the self-made SNEDDS reached up to nearly 100% in 45 min.Conclusion: The optimal formula of atorvastatin calcium SMEDDS optimized by D-optimal mixture design can improve the drug dissolution rate effectively.

Objective To investigate the effect of inhibition of endoplasmic reticulum stress (ERS) in ischemic preconditioning-induced cerebral ischemia tolerance.Methods A total of 120 adult male SpragueDawley rats were randomly allocated into three groups:sham operation,global cerebral ischemic and ischemic preconditioning groups (ischemic preconditioning for 3 minutes,and global cerebral ischemia for 15 minutes after 2 days).Three time points (day 1,day 3 and day 7) were set.Sugawara method was used to observe the changes of neurological behavior in rats.TUNEL staining was used to observe the conditions of cortical neuronal apoptosis.Immunofluorescence staining and Western blot analysis were used to detect the expression levels of ERS-related protein CHOP,GRP78,and caspase-12.Results The neurological behavior score showed that the sham operation group did not have neurological deficits.Both the global cerebral ischemic group and the ischemic preconditioning group had obvious neurological deficits,and they improved gradually with the passage of time,but after modeling,the neurological scores at each time point in the global cerebral ischemic were significantly lower than those in the ischemic preconditioning group:at day 1∶11.00 ±0.63 vs.14.33 ±0.33 (t =21.74,P＝0.001); at day 3∶ 12.17±0.31vs.15.17±0.48 (t=27.93,P =0.000); at day 7:14.67±0.49 vs.16.33 ±0.33 (t =7.81,P=0.020).TUNEL staining showed that at day 7 after ischemia,the positive cell count per mm2 in the sham operation,global cerebral ischemic and ischemic preconditioning groups were 4.83 ±1.85vs.395.67± 43.43 and 146.17± 27.38 respectively (F=23.62,P=0.001).The ischemic preconditioning group was significantly lower than that in the global cerebral ischemic group (P =0.001).Immunofluorescence staining showed that at day 7 after ischemia,the numbers of positive cells of CHOP (26.50±3.89vs.82.33±4.25; P=0.000),GRP78 (15.00±2.02vs.35.67±2.99; t=0.000),and caspase-12 (22.33 ± 2.76 vs.66.50± 7.25; P=0.000) in the ischemic preconditioning group were significantly less than those in the global cerebral ischemic group.Western blotting showed that at day 7 after ischemia,the expression levels of CHOP (1.22 ± 0.38 vs.3.22 ± 0.51; t =24.50,P =0.001),GRP78 (1.78 ± 0.45 vs.3.16 ± 0.76; t =14.29,P =0.005),and caspase-12 (2.89 ± 0.53 vs.5.96 ± 0.67; t =77.73; P =0.000) in the ischemic preconditioning group were significantly lower than those in the global cerebral ischemic group.Conclusions Ischemic preconditioning demonstrated a neuroprotective effect for the second lethal ischemia,its mechanism may be associated with the relief of ERS and downregulation of ERS-related protein.

Objective To investigate the postnatal developmental rule of TrkA and ChAT\|immunoreactive(ChAT\|ir) neurons and the relationship between TrkA and ChAT\|ir neurons in the horizontal limb of diagonal band(HDB) of rats. Methods Immunohistochemistry technique combined with image analyser were used. Results TrkA and ChAT\|ir neurons localized in the neurons of basal forebrain of rats. TrkA immunostaining was present at postnatal day 1(PD1), but ChAT immunostaining was present at PD5 Most densely stained TrkA and ChAT neuronal bodies and fibers were present at PD20, while the mean grey degrees of TrkA and ChAT\|ir neurons reached to the peak. Both TrkA and ChAT began to decline at PD30 and maintain a relatively higher level in the adult. However, during aging both TrkA and ChAT\|ir neurons atrophied and became smaller than that of adult. The number of TrkA and ChAT\|ir neurons decreased 39 8% and 33 3%;the mean areas 15 7% and 12 8%; the mean grey degree values were 29 9% and 9 9%, respectively. The mean areas, grey degrees and numbers of TrkA and ChAT\|ir neurons from PD5 to aged rats had positive correlation. Conclusion The results indicate that the expression of TrkA was earlier than ChAT. The expression of TrkA and ChAT followed a very similar temporal pattern in HDB from PD5 to aged rats, suggesting that TrkA may participate in the regulation of ChAT\|ir neuronal development, differentiation, maturation and aging. The down\|regulation of TrkA and ChAT of aged rats is associated with neuronal atrophy and loss and may contribute to the pronounced vulnerability of these neurons to degeneration in aging animals and Alzheimer disease.\;

Objective To evaluate MRI measurement of basal ganglia volumes in patients with Tourette's syndrome.Methods Ten patients with Tourette's syndrome(TS)and 10 healthy volunteers were studied.Volumes of bilateral candate,putamen and pallidum were measured,and the results were analyzed using paired t test.The basal ganglia volume was normalized according to individual brain volume.The basal ganglia volumes of TS patients were compared with normal control group using independent-sample t tesL Results In 10 healthy volunteers,volumes of the left caudate,putamen,pallidum were significantly larger compared with those of the right side(P＜0.05).However,there were no significant differenees between bilateral basal ganglia volumes(P＞0.05)in TS patients.After normalized processing,the volumes oftlle left candate(7.06±0.48)cm3,putamen(8.81 ± 1.01)cm3,pallidum(2.64 ± 0.38)cm3were smaller than those of control group[caudate(11.05±1.86)cm3,putamen(9.97 ±1.11 ) cm3, paUidum (3.04 ± 0.37 ) cm3 ] (t= - 6.577, - 2.457, - 2.376, P＜0.05 ).The volume of the right caudate (7.32 ± 0.26) em3 in "IS patients was significantly smaller compared with the control group (9.81±1.83) cm3 (t = -4.258, P ＜0.01 ).However, the volumes of the right putamen and pallidum had no significant difference between two groups (P＞0.05).Conclusion The basal ganglia volumes were significantly decreased in patients with TS.MRI volumetric measurement was an important tool for evaluating pathologic changes of TS.

Objective To evaluate the variables which can be used as prognostic factors in predicting the outcome of Graves disease(GD)after treatment with antithyroid drugs.Methods We performed a retrospective audit of 204 patients with newly diagnosed Graves disease consecutively at the Ruijin Hospital.Results Overall,110 patients(53.9%)were considered to be treatment failures.Age at the time of diagnosis was(31.0±12.2)years in the successful group and(36.3±14.0)years in the failure group.Free T3(FT3)was(25.60±9.52)pmol/L and(19.16±6.38)pmol/L in the failure and the successful group(P=0.001).FT3 to FT4 ratio and thyrotrophin recptor antibody(TRAb)levels were higher in the failure group(P=0.001).Logistic regression analysis showed that thyroid size,FT3 to FT4 ratio and TRAb at the time of diagnosis were associated with failure outcome.The patients reached euthyroid state at 3,6,9 and 12 months respectively and in the failure group the patients with continued thyrotropin suppression were more than those in the successful group(P=0.001).Conclusions Graves disease patients with large thyroid size,high levels of TRAb and FT3 to FT4 ratio before drug treatment are more likely to fail to respond to antithyroid drug treatment.We also found that patients with continuing thyrotropin suppression and attainmen of euthyroid state in the course of treatment had low remission rate and prolonged therapy.

Objective To explore the mechanism of persistent thyrotropin suppression in euthyroid patients with Graves′ disease after antithyroid drugs (ATD) treatment. Methods A prospective clinical study was performed in 122 patients with newly diagnosed Graves′ disease. All the patients were treated with 30 mg methimazole or 300 mg propylthiouracil daily, to whom L-T4was added, aiming at normalizing FT3 and FT4 but avoiding elevated TSH level. When the patients were clinically and biochemically euthyroid for at least 3 months, their blood levels of thyroid hormones, TSH, TSH receptor antibody(TRAb) and thyroid peroxidase antibody(TPOAb) were detected again and the cases were divided into two groups according to negative or positive TRAb. Results After treatment as long as (7.1±1.1) months, stable euthyroid status was restored for 3 months. When the patients reached the euthyroid state, 64 of them still had detectable TRAb levels, and 58 became negative TRAb. The two groups had similar levels of FT3 and FT4, but patients with positive TRAb had lower TSH level than patients with negative TRAb[0.044 mIU/L(0.001-4.163 mIU/L) vs 1.749 mIU/L(0.079-4.646 mIU/L),P＜0.01]. In addition, the TSH level was negatively correlated with TRAb level (r=-0.539, P＜0.01), and not with FT3, FT4 levels or other factors. Conclusion The present study showed that elevated TRAb level is associated with persistent suppression of TSH in patients with Graves′ disease after being rendered euthyroid. This finding may be due to the binding of TRAb to pituitary TSH receptor.

Objective To explore the advantages of the technique of bile duct mini-incision (BDM) for stone removal in choledocholithiasis,and to further clarify the indications for T tube insertion during surgery.Methods 85 BDM operations were performed.The use of MRCP (Magnetic resonance cholangiopancreatography),Advantage Workstation AW4.2 0.7sdc software,choledochoscopic imaging system and illustrations were used to study the applicability of the BDM technique in stone removal.Results The width of common bile duct (CBD) was usually over 8 mm in the patients with choledocholithiasis,and the width was related to the number and size of the stones.In the patients who had a CBD width of over 11mm (n 16),the MRCP stone imaging area (MRCP-SIA) was significantly larger when compared with that [(148±67)mm2 vs.(47±31)mm2,P＜0.05] in the patients (n=14) with CBD width of less than 11 mm.T tube insertion for secondary choledochoscopic examination should be performed when the stones were non drifting,multiple,and closely related to the lower part of CBD indicating difficulty in complete stone removal.Conclusions Unnecessary T tube insertion could be avoided by the BDM technique for stone removal which was especially suitable for patients with early diagnosis of choledocholithiasis.T tube insertion should only be performed in patients with difficulty in complete stone removal and in other complicated situations.

Objective To investigate the effect of the asthmatic mice's contents of nuclear factorerythroid-2-related factor 2,Nrf2 and HO-1 reated with curcumin in lung tissue.Methods All 45 mice were divided into three teams randomly,the normal mice,the asthmatic mice and the curcumin mice group.We tested the expression of Nrf2 and HO-1 of three mice teams in lung by immunolfluorescence technique.We tested the protein contents of Nrf2 and HO-1 of the three teams in the lung tissue by Western blot.We tested the binding activity of Nrff2 and ARE of the three teams in lung by EMSA.Results The expression of Nrf2 and HO-1 in curcumin group was significantly higher than that in asthma group and normal control group by immunolfluorescence technique.There was no sigrnificant difference in content of cytoplasm Nrf2 protein in lung tissue between three groups by western blot(P ＞ 0.05).The content of nuclear Nrf2 and HO-1 protein in the lung tissue of the curcumin group was significantly higher than that in the other two groups,the difference is statistically significant (Nrf2,P ＜0.05;HO-1,P ＜0.01).The binding activity of Nrf2-ARE in lung tissue of curcumin group was significantly higher than that of asthma group and control group,with statistical significance(P ＜ 0.05).Conclusion Curcumin can increase the protein contents of the Nrf2 and HO-1 of mice and enhance the expression of them.

Objective To investigate the effect of the asthmatic mice's contents of NF-κB、IκB、p-IκB treated with curcumin.Methods Thirty Balb/c mice were divided into three groups randomly,the normal mice,the asthmatic mice and the curcumin mice.The bronchial hyperresponsiveness of the three groups were exanined by lung function.The NF-κB 、IκB 、p-IκB content of three teams were tested.Results The content of cytoplasm NF-κB in asthmatic mice was lower than the control (P ＜ 0.01).However,the content of cytoplasm NF-κB in curcumin team was more than the asthmatic mice (P ＜ 0.05).In the other hand,The content of nuclear NF-κB in asthmatic mice was more than the control(P ＜0.01).However,the content of nuclear NF-κB in curcumin mice was lower than the asthmatic mice (P ＜ 0.05).The content of cytoplasm p-hκB in asthmatic mice was more than the control and the content of IκB was lower than the control(P ＜ 0.01).Howerer,the content of IκB in curcumin team have much more than the asthmatic mice and the content of p-IκB have much lower than the control(P ＜ 0.01).Condusion Curcumin alleviates the airway hyperresponsiveness of the asthmatic mice through the suppression of NF-κB transcribe to the nuclear via alleviating the phosphorylation of I-κB.