Parkinson's disease (PD) is a common neurodegenerative disorder associated with aging. Great progresses have been made toward understanding the pathogenesis over the past decades. It seems that both genetic factors and environmental factors contribute to PD, while the precise pathogenesis still remains unknown. Recently, increasing evidence has suggested that autophagy dysregulation is closely related to PD. Dysregulation of the autophagic pathways has been observed in the brains of PD patients or in animal models of PD, and a number of PD-associated proteins, such as a-synuclein, Parkin and PINK1, were found to involve in autophagy, suggesting a link between autophagy and pathogenesis of PD. In this review, we summarized the role of PD-associated proteins in autophagy pathways. In addition, we described the efficacy of autophagy-modulating compounds in PD models and discussed promising strategies for PD therapy.
Animals ; Autophagy ; Humans ; Parkinson Disease ; physiopathology ; Protein Kinases ; metabolism ; Ubiquitin-Protein Ligases ; metabolism ; alpha-Synuclein ; metabolism

Parkinson's disease (PD) is a common neurodegenerative disorder associated with aging. Great progresses have been made toward understanding the pathogenesis over the past decades. It seems that both genetic factors and environmental factors contribute to PD, while the precise pathogenesis still remains unknown. Recently, increasing evidence has suggested that autophagy dysregulation is closely related to PD. Dysregulation of the autophagic pathways has been observed in the brains of PD patients or in animal models of PD, and a number of PD-associated proteins, such as a-synuclein, Parkin and PINK1, were found to involve in autophagy, suggesting a link between autophagy and pathogenesis of PD. In this review, we summarized the role of PD-associated proteins in autophagy pathways. In addition, we described the efficacy of autophagy-modulating compounds in PD models and discussed promising strategies for PD therapy.

Objective To investigate the effect of hydrogen sulfide (H2S) on the cholesterol efflux and ATP-binding cassette transporter A1 (ABCA1) expression in foam cells .Methods RAW 264 .7 macrophages were incubated with oxidized low density lipoprotein to induce foam cells .Foam cells were incubated with H2S donor sodium hydrosulfide .Cholesterol efflux from macropha-ges was tested by labed cholesterol .The cellular levels of free cholesterol (FC) ,cholesterol ester (CE) and total cholesterol (TC) were measured by high performance liquid chromatography assays .The mRNA and protein expressions of ABCA1 were detected by Real-time PCR and Western blot .Results Compared with the foam cells ,the rates of cholesterol efflux were significantly in-creased ,the levels of TC ,FC ,CE and CE/TC ratio were significantly decreased(P<0 .05) and expression of ABCA1 was signifi-cantly increased by treatment with H2S in dose-and time-dependent manner(P<0 .05) .Conclusion H2S up-regulates of expres-sion ABCA1 and promotes cholesterol efflux in RAW 264 .7 macrophage-derived foam cells .

To study the stimulation effect to the growth of Bifidobac te rium sp. A04, 4 kinds of oligosaccharide, 8 kinds of Chinese traditional medi cine and 4 kinds of food raw materials were used. The results indicates that so ya bean oligosaccharide is the most effective (P

The guiding thoughts and purpose of the curicular quality evaluation are expounded in this article: under the guide of Deng Xiaoping's theory adhering to the army and national political system and policy of education,adhering to Deng Xiaoping's"three faceto"educational view and methodology,we carry out the evaluation to promote the construction,to realize the purpose of course construction,teaching,learning,administration,competmon and finally to mlprove the curiculum teaching quality.

ObjectiveTo prospectively investigate the impact of short-time response on survival of concurrent chemotherapy and thoracic three-dimensional radiotherapy (CCTTRT) for stage Ⅳ non-small cell lung cancer (NSCLC). Methods From Jan.2003 to Oct.2010,201 patients with pathologically or cytologically proven stage Ⅳ NSCLC were included.All patients received platinum-based chemotherapy.Of the 167 patients eligible for analysis,the median number of chemotherapy were 4 cycles.The median dose for planning target volume (PTV) of thoracic primary tumor was 63 Gy.Response was scored according to WHO criteria. Survival was calculated by Kaplan-Meier method and compared using the Logrank. Cox regression model were used to examine the effect of response on overall survival.ResultsThe follow-up rate of 201 patients was 97.5％.with 201,170 and 134 patients finished ＜ 1,1 -2 and ≥3 years' follow-up.For the 167 patients eligible for analysis,the CR,PR,NC and PD rate of primary tumor was 5.4％,65.9％,21.0％ and 7.7％,respectively.The effective group ( CR + PR) and ineffective group ( NC + PD) was 71.3％ and 28.7％,respectively.The median survival time (MST) for patients with CR,PR,NC and PD was 22.6,13.4,8.8 and 4.8 months,respectively ( χ2 =44.79,P =0.000).The MST for effective and ineffective group was 13.9 and 7.6 months,respectively in the whole group ( χ2 =8.3 0,P =0.004 ),12.1months and 7.3 months in those treated with 2 - 3 cycles chemotherapy ( χ2 =7.71,P =0.007 ),and 13.9months and 7.9 months in those treated with 2 -5 cycles chemotherapy and radiation dose to PTV ≥36 Gy ( χ2 =4.00,P =0.045 ).No significant MST difference was detected between patients of effective group and ineffective group treated with 4 -5 cycles chemotherapy ( χ2 =0.67,P =0.413),or those treated with 4 -5 cycles of chemotherapy and radiation dose to primary lesion ≥36 Gy (χ2 =0.00,P =0.956).Multivariate analysis showed that 4-5 cycles of chemotherapy and CR and PR achieved in primary tumor (β =0.182,P=0.041 ) were independent favorable factors for survival. Conclusion CCTTRT can improve local control,and prolong the survival time for Stage Ⅳ NSCLC.

Objective To prospectively evaluate the survival of different metastasis organs with concurrent chemotherapy and thoracic three-dimensional radiotherapy (CCTTRT) for stage Ⅳ non-small cell lung cancer (NSCLC).Methods Two hundred and one patients of stage Ⅳ NSCLC were enrolled from January,2003 to July,2010.Of the 182 patients eligible for analysis,The number of patients with single-organ metastasis or multiple-organ metastasis was 107 and 75,respectively.Patients were treated by platinum-based chemotherapy,the median number of cycle was 4.The median dose to planning target volume of primary tumor (DTPTv) was 63 Gy.Survival was calculated by Kaplan-Meier method and compared using the Logrank.Results The follow-up rate of 201 patients was 97.5％.with 201,170 and 134 patients finished ＜ 1,1 -2 and ≥3 years'follow up.Of 182 patients,the 1-,2-,and 3-year overall survival (OS) rate and median survival time (MST) was 41.0％,17.0％,10.0％ and 10.5 months,respectively ;with single-organ metastasis and multi-organ metastasis were 50％,20％,14％ and 13 months and 29％,12％,0％ and 8.5 months ( x2 =10.10,P =0.001 ),respectively; compared with multi-organ metastasis,the 1-,2-,and 3-year OS arte and MST of patients with bone,lung metastasis only was 58％,25％,16％ and 14 months (x2 =10.42,P=0.001 ) and 49％,21％,21％ and 11 months (x2 =6.39,P=0.011 ) respectively;patients with brain metastasis only did not show advantage of survival comparing with patients with multi-organ metastasis (49％,8％,0％ and 12 months and 29％,12％,0％ and 8 months,respectively;x2 =0.71,P =0.401 ) ;the 1-,2-,and 3-year OS rate and MST was 63％,23％,19％ and 15 months and 42％,15％,0％ and 10 months,respectively for patients with single-organ metastasis and multi-organ metastasis patients who accepted 4 - 5 cycles of chemotherapy ( x2 =6.47,P =0.011 ) ; for patients under the same metastasis and 4 - 5 cycles of chemotherapy,no matter whether single-organ or multiple-organ metastases,the 1 -,2-,3-year OS rate and MST of patients with enough radiotherapy on DTPTV ≥63 Gy were better than patients without enough radiotherapy ( DTPTV ＜ 63 Gy ) ( 71％,25 ％,25％ and 16.8 months and 33％,17％,0％ and 10.5 months,respectively;x2 ＝4.73,P =0.030 ;54％,21％,0％ and 14.3 months and 29％,10％,0％ and 7.6 months,respectively,x2 =8.16,P =0.004).The MST of liver metastases was 6 months,there was significantly difference when comparing with non liver matastasis ( x2 =17.21,P =0.000).Conclusions It is very important to treat stage Ⅳ NSCLC with CCTTRT,especially patients with single-organ metastasis.Liver metastases is a unfavorable prognostic factor.

Objective To evaluate the overall survival and safety among patients for stage Ⅳ non-small cell lung cancer (NSCLC) treated with concurrent chemotherapy and thoracic three-dimensional radiotherapy (CCTTRT).Methods From Jan.2003 to July 2010,201 patients with stage Ⅳ NSCLC were included.All patients were treated with CCTTRT.Those patients who received only one cycle chemotherapy were not included in survival analysis,but analysis of toxicity.One hundred and eighty-two patients were eligible for survival analysis.All patients received platinum-based two-drug chemotherapy.The median number of cycles was 4.The median dose to planning target volume of primary tumor ( DTPTV ) was 63 Gy.Treatment-related gastrointestinal and hematological toxicity were scored according to WHO criteria.Radiation-related pneumonitis and esophagitis were evaluated according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTC) version 3.0.Survival was calculated by Kaplan-Meier method and compared using the Logrank.Cox regression model was used to examine the effect of CCTTRT on overall survival.Results The follow-up rate of 201 patients was 97.5％.with 201,170 and 134 patients finished ＜ 1,1 -2 and ≥3 years' follow-up,respectively.Of the 182 patients eligible for survival analysis,further stratified analysis showed that the 1-,2-and 3-year overall survival rate and median survival time (MST) was 54％,20％,13％ and 14.3 months,respectively for patients treated with concurrent 4 -5 cycles chemotherapy and CCTTRT,and 66％,23％,19％ and 16.1 months,respectively for those treated with 4 -5 cycles chemotherapy and DTPTV ≥ 63 Gy.Under similar chemoradiotherapy intensity,the MST of patients with single organ metastasis was significantly longer than that with multiple organ metastases ( 13.0 months versus 8.5 months,x2 =10.10,P =0.001 ).For patients eligible for survival analysis and received 4 - 5 cycles of systemic chemotherapy,MST of patients treated with DTPTV≥63 Gy was significantly longer than those treated with DTPTV ＜63 Gy[14.9 months vs.8.4 months (x2 ＝20.48,P =0.000) and 16.1 months vs.8.8 months ( x2 =11.75,P =0.001 )].For patients with single organ metastasis,MST was 16 months for those treated with DTPTV ≥63 Gy and 9 months for those with DTPTV ＜63 Gy (x2 =10.51,P=0.000) ;for patients with multiple organ metastasis,it was 11 months and 7 months,respectively ( x2 =7.90,P =0.005 ).Multivariate analysis showed that concurrent 4 - 5 cycles chemotherapy and DTPTV ≥63 Gy (β =0.243,P=0.019) and improved KPS (β =1.268,P=0.000) were independent factors for survival.For the whole group,45％ patients had Grade 2 -3 gastrointestinal toxicity,35.0％ grade 3- 4 leukopenia,18％ grade 3- 4 thrombocytopenia.15.0％ grade 3- 4 anemia,9.5％ Grade 2 - 3 radiation pneumonia and 13.4％ radiation esophagitis,respectively.Conclusions For stage Ⅳ NSCLC,CCTTRT can prolong survival time with acceptable toxicity.Radiotherapy to thoracic primary tumor should be under consideration.

Objective To investigate the expression and significance of elastin and fibulin-5 in anterior vaginal tissue of women with pelvic organ prolapse (POP). Methods Between November 2006 and June 2008, 68 patients with POP underwent surgical treatment in Shengjing Hospital of China Medical University were enrolled in this study, who were classified into 10 patients with grade Ⅰ , 21 patients with grade Ⅱ , 25 patients with grade Ⅲ and 12 patients with grade Ⅳ in accordance with pelvic organ prolapse quantitation (POP-Q). Meanwhile, 18 cases with early cervical cancer at stage of Ⅰ b were treated by total hysterectomy and bilateral salpingo-oophorectomy, their anterior vaginal tissues were selected as controls. Immunohistochemical staining was performed to detect the expression of elastin and fibulin-5. Results (1 ) Elastin and fibulin-5 were mainly expressed at extracellular matrix(ECM). (2)The positive rate of fibulin-5 expression in anterior vaginal wall were 5% (2/37 ) in grade Ⅲ/Ⅳ and 26% (8/31 ) in grade Ⅰ/Ⅱ POP patients, which reached statistical difference (P = 0. 035). However, no statistical different expression was found between postmenopausal (13%, 8/60) and non-menopausal patients (2/8), vaginal delivery ≤ 2 (19%, 5/27 ) and ＞ 2 patients (12%, 5/41, P ＞ 0. 05 ). (3 ) The positive rate of elastin expression in anterior vaginal wall in POP group was 31% (21/68), which was significantly lower than 72% (13/18) of control group (P = 0. 002). Among POP group, 19% (7/37) of elastin expression in grade Ⅲ/Ⅳ POP was significantly lower than 45% (14/31 ) in grade Ⅰ/Ⅱ of POP patients. However, no statistical difference was found between postmenopausal (30%, 18/60 ) and non-menopausal patients (3/8 ), vaginal delivery ≤ 2 (26%, 7/27) and ＞2 patients(34%, 14/41, P＞0. 05). (4)In POP group, both positive expression of fibulin-5 and elastin of anterior vaginal wall was in 6 cases, both negative expression of fibulin-5 and elastin was in 43 cases. It was illustrated that elastin and fibulin-5 had an positive relationship (P = 0. 031 ). Conclusion The decreased expression of elastin and fibolin-5 was correlated with degree of POP, which indicated that elastin and fibulin-5 may play a role in the pathogenesis of POP.

Objective To discuss clinical effects of early (<48 hours after injury) fraeture exter-nal fixation in treatment of severe traumatic brain injury (TBI) combined with extremity fracture. Meth-ods The study involved patients with no statistical difference in aspects of age, sex, GCS, fracture ,distri-bution and general condition. According to different treatment methods at early stage (<48 hours), the pa-tients with TBI were divided into Group A (early extremity fracture external fixation) and Group B (early extremity fracture traction or cast immobilization). A comparative observation was done on complications in-cluding bedsore, pneumonia and deep venous thrombosis and on duration in ICU, hospitalization, time for fracture healing and mortality in two groups. Results Incidence rate of bedsore, pneumonia, deep ve-nous thrombosis and mortality in Group A was lower than that in Group B (P<0.05), and Group A had shorter time for ICU, hospitalization and fracture healing (P < 0.05). Conclusion For patients with se-vere TBI combined with extremity fracture, early fracture external fixation is more effective to reduce com-plications, shorten the recovery time and reduce mortality, compared with conservative methods.