γ-Secretase is aⅠtransmembrane protease associated with Alzheimer disease(AD), and including four subunits:presenilin,presenilin enhancer-2,anterior-pharynx-defective1 and nicastrin. In recent studies,the ultra-high-resolution cryo-electron microscope has been used for the first time, revealing the humanγ-secretase″horseshoe″,the three-dimensional structure and the arrangement of the subunits. This technique has shed light on the regulation of the enzyme pathway and mechanism. In addition,the γ-secretase modulators,including non-steroidal anti-inflammatory drugs,have been shown in vitro to inhibit γ-secretase activity and selectively reduce the level of Aβ42 against AD. They have provided an effective approach,with broad prospects for development. Studies in this area have become a hot topic in recent years. Here we summarized the γ-secretase subunits regulatory pathways, humanγ-secretase fine three-dimensional structure andγ-secretase modulators .

Objective To explore the effect of early melodic intonation speech training on Broca aphasia. Methods 22 patients with Broca aphasia were trained with the early melodic intonation training program. They were evaluated with China Rehabilitation Research Center aphasia examination before and after the treatment. Results There were significant differences in auditory comprehension, repetition, oral reading, speaking, reading and calculation (P<0.05), but no significant difference in description, copying, and dictation (P>0.05). Conclusion Early melodic intonation speech training can improve the speech and reading in patients with Broca aphasia.

Objective: To study the anti inflammatory, antipyretic and analgetic actions of Kangleifengshi capsules. Methods: The anti inflammatory action was observed by adjuvant arthritis and other inflammatory models. The antipyretic action was surveyed by pyretic rat induced by yeast. The analgetic effect was tested by sprain mice. Results: The experiments proved that the capsule has significant preventing and treating effects on rat adjuvant arthritis, strong inhibition on many kinds of inflammatory models, antipyretic action on pyretic rat induced by yeast and notable angalgetic action on sprain mice induced by acetic acid. Conclusion: Kangleifengshi Capsules has better anti inflammatory, antipyretic and analgetic effects.

Objective To analyze the disease burden of Yi nationality.Methods Disability adjusted life years(DALY) was used as the measurement indicator of disease burden.Results The male had greater Years of Life Lost to Premature Death(YLL)per thousand populations,Years of Lived with Disability(YLD) and DALY than did the female almost in each age group.The burden of Neuropsychiatric conditions was the heaviest.The burden of Yi nationality was heavier than Han nationality in diseases during perinatal period and digestive diseases.However,the disease burden of malignant neoplasm of Han nationality was heavier than Yi nationality.Conclusion The prevention and treatment of neuropsychiatric conditions,diseases during perinatal period and digestive diseases should be enhanced in Yi nationality.

Objective To evaluate the activation patterns in the cortexes of expressive aphasics after stroke so as to explore the pathogenic mechanism of expressive aphasia.Methods Blood oxygen level dependent functional magnetic resonance imaging (BOLD-fMRI) was the method of choice.It was administered to 9 subjects with expressive aphasia at 1 to 3 months post-stroke onset and to 10 healthy controls.Active areas in the patients' brains were observed using a block-designed picture-naming task,and language function was tested with the China Rehabilitation Research Center's aphasia examination (CRRCAE).The control group received BOLD-fMRI only.SPM8 software was used to process the fMRI data.Results Differences were observed in the mapping of activated areas between the two groups,but many activated areas showed no difference.Significant differences in activation were observed in areas associated with vision,language and cognition,including the bilateral inferior frontal gyrus,the bilateral superior temporal gyrus,the bilateral insula,the bilateral basal ganglia,the left superior frontal gyrus,the left middle frontal gyrus,the left precentral gyrus,the left thalamus,and the left middle temporal gyrus.All the patients had activated cortex regions associated with visual processing in the left and/or right hemisphere,such as the middle frontal gyrus,the middle temporal gyrus,the lingual gyrus and the fusiform gyrus.The activation volumes in the left hemisphere were significantly smaller than those in normal adults.Regions related to language such as the left inferior frontal gyrus (Broca's area),the left middle frontal gyrus,and the right inferior frontal gyrus (the mirror region of Broca's area) were activated in some of them.While the activation frequency,activated volume and activation intensity generally were all less in the patients than in the controls,the activation intensity in the right superior temporal gyrus,the bilateral superior parietal lobule and the left inferior temporal gyrus were stronger.Conclusions Language production may be associated with multiple,interconnected regions.The right hemisphere participates in natural language processing.Aphasia damages both linguistic and cognitive areas,reducing activation in Broca's aphasia.Activation areas in the left hemisphere and the right inferior frontal gyrus decrease significantly,while some regions in the right hemisphere are relatively more activated.The right inferior frontal gyrus may play a different role in language recovery at different periods of aphasia after stroke.

ObjectiveTo investigate the potential of human amnion-derived mesenchymal stem cells to differentiate into insulin secreting cells in vitro.MethodsThe hAD-MSCs were isolated from human amnion by trypsin-collagenase digestion.The phenotype of the isolated cells was identified by flow cytometry and immunocytochemical staining.The 3rd generation cells were inoculated at density of 2.5 × 106 unit/ml or 5 × 105 unit/ml in 6 well plates or preset coverslip 24 well plates.Induced groups were treated in serum-free HG-DMEM with 10 mmol/L nicotinamide and N2 supplement.The cells in the non-induced groups were incubated in LG-DMEM supplemented with 10％ fetal bovine serum.At days 7,14 and 21 after induction,insulin and β2 microglobulin was determined by immunocytochemical stain,the content of insulin in the culture supernatant was assayed by radioimmunoassay,and insulin mRNA and PDX-1 mRNA were detected by reverse transcriptase-polymerase chain reaction.Results( 1 ) The hAD-MSCs highly expressed CD29,CD44,CD73,CD166,and vimentin.( 2 ) At 7,14,and 21 days,the percentages of insulin-positive cells in hAD-MSCs induced groups were 74.67％ ± 1.53％,75.00％:1.00％,and 74.33％ ±1.53％,respectively.Contents of insulin in the supematant of hAD-MSCs induced groups were ( 331.62 ± 1.76 ),( 330.50 ± 1.22 ),and ( 331.65 ± 0.48 ) μIU/ml,respectively,but non-induced groups were negative.(3) PDX-1 mRNA and PDX-1 protein were expressed before and after the induction of hADMSCs,but insulin mRNA was expressed only in the induced groups.( 4 ) Both hAD-MSCs induced groups and non-induced groups expressed β2 microglobulin ( all P ＞ 0.05 ).ConclusionThe hAD-MSCs have a potential of differentiating into ISCs and thus may become a new cell source of therapy for type 1 diabetes.

AIM: To compare the methods of two currently employed isolation methods for endothelial progenitor cells (EPCs): from total peripheral blood mononuclear cells (PBMCs) and from enriched CD133~+ cells, by defining the cell morphology, phenotype, reproductive activities and function in vitro, providing a reference for clinic application. METHODS: PBMCs from the healthy subjects were used for CD133~+ sorting or not. The two groups of isolated cells were suspended in complete medium M199 for 7 d to 14 d. EPCs phenotype were characterized by FACS. The proliferation of differentiated EPCs was studied by MTT assay, and VEGF concentration was measured using an ELISA kit. Matrigel experiment and migration assay were imitated vascularization in vivo. RESULTS: PBMCs produced more colony-forming units (CFU) than CD133~+ cells from the same volume of blood (P<0.01). From 7 d to 14 d, the two groups show decreased expression of hematopoietic stem cell markers and increased level of endothelial markers, but CD144~+ cells in CD133~+ group were lower than those in PBMCs groups (P<0.01). Cells in PBMCs group secreted more VEGF than that in CD133~+ group on 7 d (P<0.01). Compared to CD133~+ group, PBMCs group showed more potential of proliferation and vascularization in vitro. CONCLUSION: CD133~+ sorted cells show a lower capacity of differentiation, secretion, proliferation and vascularization in vitro, which is unable to differentiate to mature endothelial cells, indicating that it's not a preferential way to obtain EPCs for clinic therapy.

Objective To investigate the efficacy of two different methods of catheter balloon dilatation therapy in treating cricopharyngeal achalasia and benign strictures,and to correlate balloon capacity with improve-ments in swallowing function. Methods Twenty-three cricopharyngeal achalasia patients and 7 with benign stric-tures of the cricopharyngeal muscles were diagnosed using videonuoroscopic swallowing study(VFSS).All cases re-ceived active dilatation or passive balloon dilatation therapy,combined with manipulation,indirect training,direct training and feeding instruction.Efficacy and the correlation were evaluated using VFSS and a swallowing function scale. Results Passive and active dilatation had the same efficacy.The correlation coefficient between balloon ca-pacity and swallowing function was 0.92 1.Re-evaluation using VFSS showed that opening of the cricopharyngeal muscles had improved significantly.Conclusions Balloon catheter dilation is an effective treatment for cricopha-ryngeal achalasia and benign strictures.The improvement in swallowing function is highly correlated with balloon ca-pacity in balloon dilatation therapy.Comprehensive treatment for dysphagia would provide better outcomes.

Two isolation methods for sorting of endothelial progenitor cells (EPCs): from peripheral blood mononuclear cells (PBMCs) and CD133(+) enriched cells were compared, by defining the cell morphology, phenotype, reproductive activities and function in vitro, to provide a reference for clinical application of EPCs. PBMCs from healthy subjects were used either directly for cell culture or for CD133(+) sorting. The two groups of cells were cultured in complete medium 199 (M199) for 7 to 14 days and the phenotypes of EPCs were analyzed by FACS. The proliferation of differentiated EPCs was studied by MTT assay, and the VEGF concentration was measured using an ELISA kit. ECM gel experiment and migration assay were performed in vivo. The results showed that PBMCs produced more colony-forming units (CFU) than CD133(+) enriched cells from the same volume of blood (P<0.01). From day 7 to 14, the two groups showed decreased expression of hematopoietic stem cell markers and increased level of endothelial markers, but CD144(+) cells in CD133(+) group were less than in PBMCs group (P<0.01). PBMCs group secreted more VEGF than CD133(+) group on the day 7 (P<0.01). As compared with CD133(+) group, PBMCs group had more potent potential of proliferation and vascularization in vitro. It was concluded that CD133(+) sorted cells showed a lower capacity of differentiation, secretion, proliferation and vascularization in vitro, suggesting that CD133-negative cells may be a preferential way to get EPCs for clinical therapy.

AIM:To investigate the activity of NF-?B in peripheral blood mononuclear cells (PBMCs) from patients with Graves disease (GD) and the significance in immunopathogenesis of GD.METHODS:Peripheral blood was collected from 22 untreated GD,20 treated GD with tapazole more than 1 year,and 25 healthy volunteers. PBMCs were isolated from the blood by histopaque-1077 density-gradient centrifugation. The activity of NF-?B in PBMCs was analyzed using gel electrophoretic mobility shift assay (EMSA). The contents of IL-1?,IL-6 and TNF-? were tested by radioimmunoassay.RESULTS:The activity of NF-?B in PBMCs of untreated GD group was increased remarkably,compared with that in the treated group and control (P