Objective To investigate the effect of Akt pathway inhibitor AZD5363 on cell proliferation and invasion of QBC939 and RBE cholangiocarcinoma cells and the mechanism.Methods Western blotting was used to detect Akt and downstream protein and mTOR protein expression in two cancer cell lines after process by AZD5363.Inhibition rate and cytotoxicity was tested by CCK-8 assay,and Transwell assay was used to evaluate the invasive ability of cancer cells.Results QBC9393 cell exposed to AZD5363 LD50 drug concentration (24 ±9) was significantly different compared with control group (t =4.47,P ＜ 0.05),RBE cells LD50 drug concentration (21 ± 8) was significantly different compared with control (t =4.41,P ＜ 0.05).Tumor invasion capacity of QBC939 in drug concentrations of 20 μmol/L (63 ± 12) and 0 μmoL/L (271 ± 27),the difference was statistically significant.RBE exposed AZD5363 upon drug concentrations of 20 μmol/L (58 ± 23) and 0 μmol/L (235 ± 21),the difference was statistically significant.AZD5363 promotes phosphorylation of mTOR in QBC939.Conclusions AZD5363 inhibits the proliferation and migration,inhibiting the phosphorylation of Akt and its downstream molecules.AZD5363 promotes phosphorylation of mTOR in QBC939.

·AlM:To evaluate the visual and anatomic outcomes of intravitreal ranibizu mab injections for myopic choroidal neovascular ization ( mCNV) in Chinese patient s.
·METHOD S: This study is ar etrospective case.Thri ty-five p atients treated for mC NV were included in this study.Their eyes were treated with a single intravitreal injection of 0.5 mg ranibizumab following a pro re nata ( PRN) regimen indicated by persistent or recurrent CNV. Best correc te d visual acuity ( BCVA ) , CNV findings on fundus fluorescen t angio graphy ( FFA ) , central retinal thickness ( CRT ) on optical coherence tomography ( OCT ) , total number of treatments, and complications were evaluated.
· RESULTS:The mean follow-up duration was 20mo (range 16-24mo).Twenty-eight patients (80%) were followed up for more 22mo.The mean baseline BCVA was 0.74 logarithm of the minimum angle of resolution (logMAR) [standard deviation (SD) 0.23] and improved significantly to 0.49 logMAR ( SD 0.31 ) ( P<0.001, Wilcoxon signed-rank test) after treatment.At the final months of follow-up, 21 of the 35 eyes (60%) showed an improvement of 2 lines or more in BCVA, 13 eyes ( 37%) remained unchanged, and 1 ey e (3%) had a deterioration of 2 lines or more.Mean CRT decreased from 297 μm ( SD , 72 ) at baseil ne to 228 μm ( SD, 61 ) at the final follow-up (P<0.001, paired t-t est). During follow-up, the mean number of repeat injections was 3.2 ( SD, 0.94;range, 1-7 injections).No drug-related complications were observed after treatment.
· CONCLUSlON:The long-term outcomes observed in this study suggest that intravitreal ranibizumab is safe and effective for treating mCNV.

Objective To summerize the experiences of using random flaps to reconstruct soft tissue defects of the periorbital region.Methods Periorbital soft tissue defects in 65 patients underwent reconstruction surgery by random flaps with pedicle 1.0～2.5 cm in width.The length of the flap ranged from 1.0 cm to 3.5 cm,with the rate of length to width less than 2.5:1.Detail plans on flap and incision design were made based on the aesthetic and functional problems.Results Phenomena of blister and purplish red in the edge or the distal area of the flaps were observed in 3 cases,and were disappeared after corresponding treatment.The other flaps survived and the wound healed primarily after operation.The color and the texture of the flaps matched well to the adjacent tissues with satisfied function and aesthetic Results .Conclusion Random flap is an ideal substitute to repair periorbital soft tissue defects.

Objective To explore the morphological characteristics and change rule of thoracic joint angles in children aged from 10 to 12 years through thinner CT scanning and 3D reconstruction,and to provide theoretical basis for early diagnosis,treatment and prevention.Methods Totally 30 normal cases aged from 10 to 12 years were admitted into this study.There was no bone destruction,deformity,fractures,tumors and spine surgery involved.DICOM 3.0 data of multi-slice spiral CT (0.625 ～ 1.25 mm),ranging from T1 to T12,were used for 3D reconstruction,measurement and statistical analysis.Results The difference between left and right sagittal section angle of zygopophysis was less than 10°.There was no significant differences between T1,T11,and T12for sagittal section angle of upper zygopophysis (P ＞ 0.05).So was it between T3,T4,T9,T10 and T11 for sagittal section angle of lower zygopophysis (P ＞ 0.05).While there were significant differences between others(P ＜ 0.05).The was no significant difference between left and right coronal plane angle of zygopophysis (P ＞ 0.05).Coronal plane angle of lower and upper zygopophysis tended to be ‘ spike-like’,and the maximum points were at T7 to T9.For horizontal plane angle,left and right upper zygopophysis made significant differences between T2,T4,T8,T10 and T12 only,so did T7 lower zygopophysis (P ＜ 0.05).Horizontal angle of upper zygopophysis tended to be stable in the upper thoracic both in the left and right side,while a decreasing trend was shown in lower thoracic.Horizontal angle of lower zygopophysis showed a decreasing trend generally except individual vertebrae.Both upper and lower zygopophysis showed negative angle at T11 and T12 levels.Conclusion Thoracic joint angles(coronal,sagittal and horizontal angle) in children aged from 10 to 12 years can directly reflect the developmental regularity with growth,and it verified the tendency that horizontal facet joints of the cervical spine gradually changes to coronal facet joints thoracic spine and then changes to sagittal facet joints of lumbar spine.And the left and right side facet joints are basically symmetrical with the angle difference less than 10°.

Objective To evaluate the susceptibility of itraconazole-resistant Aspergillus fumigatus isolates to four other antifungal drugs.Methods Six strains of Aspergillus fumigatus were serially isolated from a patient with lung aspergilloma,who was resistant to itraconazole therapy.Clinical Laboratory Stan- dard Institute broth microdilution method M38-A and E-test were applied to test the susceptibility of A.fumi- gatus strains to amphotericin B,itraconazole,voriconazole,caspofungin and micafungin.Results With M38-A method,the minimal inhibitory concentration(MIC)of itraconazole was 0.5?g/mL for 2 strains and more than 16?g/mL for the other 4 strains;the MICs of amphotericin B and voriconazole were 1?g/mL and 0.25-1?g/mL respectively for all the 6 strains;and the minimal effective concentration(MEC)of caspofungin and micafungin were no more than 0.03?g/mL for all the 6 strains.Moreover,E-test results also revealed that caspofungin and voriconazole had a good antifungal activity against all the strains,including the 4 itraconazole-resistant ones.Conclusion The itraconazole-resistant A.fumigatus strains isolated from a patient with lung aspergilloma are susceptible to amphotericin B,voriconazole,caspofungin,and micafungin.

Objective To investigate the clinical and molecular pathological features of dysferlinopathy in China.Methods Four patients with limb-girdle muscular dystrophy2B(LGMD2B)and 4 patients with Miyoshi-type distal muscular dystrophy(MMD)were clinically analyzed, their skeletal muscle were biopsied and immunohistochemical stained.Four cases of each Duchenne-Aran muscular atrophy and myotis were served as controls.Results The clinical situation of dysferlinopathy was characterized by progressive muscle weakness and atrophy, consistent with progressive muscular dystrophy.Histochemical staining revealed muscle fibers degenerating, regenerating and necrosis in a varying degree.Connective tissue was seen proliferated and inflammatory cells infiltrated in the majority of cases.Immunohistochemical staining with anti-dysferlin monoclonal antibody identified the deficiency of dysferlin on the sarcolemma and in the sarcoplasm of 8 cases with dysferlinopathy.Conclusions(1)The clinical and pathological characters of dysferlinopathy are consistent with progressive muscular dystrophy;(2)Anti-dysferlin monoclonal antibody immunohistochemical staining is a reliable method to diagnose dysferlinopathy, which is worth of wide application in clinic.

[ ABSTRACT] AIM:To investigate the effect of combined treatment with gonadotropin-releasing hormone analogue ( GnRHa) and growth hormone ( GH) on the linear growth in mid-and late pubertal girls at great bone ages with central precocious puberty ( CPP) or early and fast puberty ( EFP) , and to determine the relation between C-type natriuretic pep-tide ( CNP) signaling pathway and the accelerative effect of GH on long bone growth in these girls.METHODS:Twenty-two girls were diagnosed as CPP or EFP, whose bone ages were older than 11.5 years with impaired predicted adult height ( PAH) , and divided into GnRHa treatment group ( treated with GnRHa alone, slow-release of triptorelin 60~80 μg/kg every 4 weeks, im) and combined treatment group ( treated with GnRHa and GH, 1 U/kg GH every week for 6~7 times, sc) .The height, weight and pubertal stage were determined every 3 months.At the beginning and after 6 months of the treatment, the bone age was evaluated and the serum concentrations of amino-terminal pro-C-type natriuretic peptide ( NT-proCNP), insulin-like growth factor 1 (IGF-1) and procollagen type 1 amino-terminal propeptide (P1NP) were measured. Height velocity ( HV) , height SD score for bone age ( HtSDSBA ) , PAH and the serum indexes mentioned above were com-pared at the beginning and the end of the treatment.RESULTS: After 6 months of the treatment, HV, ΔHtSDSBA andΔPAH of the girls treated with GnRHa +GH were statistically higher than those of the girls given GnRHa alone ( P <0.01).Serum concentrations of NTproCNP, P1NP and IGF-1 were not significantly different between the beginning and the end of the 6-month combined treatment.The girls treated with GnRHa alone showed a significant decrease in both serum NTproCNP and P1NP levels (P<0.05) and no significant change of serum IGF-1 level after 6 months of the treatment. CONCLUSION:In the CPP or EFP girls who are in mid-and late puberty and at great bone ages, the combined treatment with GnRHa and GH may accelerate linear growth and improve predicted adult height.This effect of GH is not attributed to the change of serum IGF-1 level, and may be related in part to the acceleration of CNP-mediated long bone growth.

Objective To discuss the relationships between serum uric acid levels and clinical stages,cognitive dysfunction in parkinson' s disease (PD).Methods Sixty patients of PD were enrolled,and their history,detailed physical examination UPDRS Ⅲ scale and mini-mental state score (MMSE) scale were performed to determine the Hoehn-Yahr stage of patients.At the same time 52 cases of healthy person were collected from the Health Examination Centers whose age,sex,and education matched with PD group as control group.The levels of serum uric acid in the two groups were examined and compared.Results The serum uric acid levels in PD group were significantly lower than those in normal control group((262.4 ±85.2) μmol/L vs (357.6 ±73.3) μmol/L) (t =1.013,P =0.005) ;There was no level correlation between different Hoehn-Yahr stage period of PD group (r =0.143,P ＞ 0.05) ; There was no significant difference on serum uric acid levels between subgroup of PD patients (F =1.014,P =0.06) ;The M MSE score between PD group and normal control group had no significant difference (26.12 ± 2.87 vs 28.32 ± 2.17) (t =1.970,P =0.073).Conclusion Low level of the serum uric is likely to be a risk factor for PD,but cannot be used to assess the severity of disease and MMSE scale used to determine the cognitive impairment in PD is not sensitive enough.

Objective To observe the surface electromyographic characteristics of the bilateral submen-tal muscles in dysphagia secondary to unilateral brainstem stroke. Methods A total of 25 subjects were recrui-ted. There were 8 stroke patients with dysphagia secondary to a left brainstem stroke and 7 stroke patients with dysphagia secondary to a right brainstem stroke. There were also 10 healthy controls matched in age and gender. The duration and peak amplitude of the submental muscle when swallowing 5 ml of warm water were recorded u-sing a surface electromyograph. Results The average amplitude of the left submental muscle in patients with a left brainstem stroke was significantly longer than that of those with a right brainstem stroke, but no significant differences in average duration were observed. Conversely, the amplitude of the right submental muscle in pa-tients with a right brainstem stroke was significantly longer than that of those with left brainstem stroke, but again there were no significant differences in duration. No significant differences were observed among the healthy con-trols. The amplitude and duration of both the affected and healthy sides of the patients were of course significantly longer or stronger than those of the healthy controls. Conclusion The swallowing function of the bilateral sub-mental muscles may be impaired among unilateral stroke survivors with dysphagia. The damage on the affected side is more severe than on the opposite side.