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 compare the result of treatment with double bands of Atlas Ti-cable and clavicular hook plate for total acromioclavicular dislocation.[Method]Fifty-two total acromioclavicular dislocation were treated with two different fixation.1)by double bands of Atlas cable(DC group,28 cases) and 2)clavicular hook plate(HP group,24 cases).There were 38 males and 14 females,39 acute and 13 chronic,all unilateral.The mean age of patients was 38.5 years(22~65).A sling of double cable was fixed through the base of the coracoid process and the clavicle at 1.5 cm upper medially above coracoid process.All hook plate were 6 holes.Coracoclavicular ligament was reconstructed routinely.[Result]All patients were available for an average duration of follow-up of 18.8 months(range,6~42 months).The results were evaluated by radiographic measurement and clinical recovery(muscle strength in upper arms,pain in shoulder,range of joint motion) by Lazcano standard.In HP group,14 patients were assessed as good,6 as fair and 4 as poor(good and fair 83%).In DC group,22 patients were assessed as good,5 as fair and 1 as poor(good and fair 96%).There was no statistical difference between the two groups.[Conclusion]In the treatment of acromioclavicular dislocation,fixation of double bands of Atlas cable is believed to be as good as hook plate fixation.Meanwhile,Atlas cable is featured with less pain followed operation,which in favor of early exercise.For it's good biocompatibility,titanium cable can be retained in body and does not need to be removed.

[Objective]To evaluate the outcome of tibiotalocalcaneal fusion in traumatic arthritis patients using the locked retrograde intramedullary nail with graft.[Method]Eighteen ankles underwent this procedure.There were 8 males and 10 females,9 with valgus and 2 with talipes equinovarus,all unilateral.The mean age of patients was 57.5 years(ranged,42~69) and the mean time between the procedure from primary trauma was 7.6 years(5~13 years).Bone graft were picked from distal fibula.The nail was inserted through a plantar approach with locking screws placed both proximally and distally.Patients were evaluated by a standardized follow-up examination using the AOFAS and the fusion outcome were observed radiographically.[Result]All patients were available for an average duration of follow-up of 13.5 months(ranged,6~22 months).All wound healed normally.The mean time of full bearing from operation was 13.6 weeks(ranged,9-16 weeks).One patient was found cerebral thrombosis after operation.One patient had moderate pain while walking on even surface,2 mild to moderate pain on uneven surface,1mild pain while standing and 14 relieved from pain.The average AOFAS score improved from 43.5(ranged,40~52) to 69(ranged,56~84) points.Solid fusion was achieved in 13 ankles(72%) after a mean follow-up of 16.8 months(ranged,12~24 months).Partial union was observed in 3 patients(17%) and non-union in 2 patients(11%).[Conclusion]Locked retrograde intramedullary nail fusion with bone graft is effective for traumatic tibiotalocalcaneal arthritis.

[Objective] To explore the effect of low intensity pulsed ultrasound(LIPUS)on the ability of repairing rabbit radius defect by cell-scaffold complex composed with bone marrow stromal cells(BMCs)and ?-tricalcium phosphate(?-TCP).[Method]Bone marrow of a rabbit was drawn and cultured by differentiation culture medium to harvest BMCs and the third generation BMCs were cultivated on ?-TCP for one week in vitro.Bilateral distal radial defects were made using a 1-mm saw in 20 mature New Zealand white rabbits.The cell-scaffold complexs stimulated by LIPUS were implanted in rabbit radial defects(cell-scaffold complexs without stimulation as control).All the rabbits were killed at 4 or 8 weeks after operation.The defect healing state was observed with X-ray and histological technic.The gray density of CA was analyzed by computer image analysis system.[Result]It was found that the callus in the experimental group grew more quickly and apparently than that in the control group.At 4 weeks after operation,there was significantly statistical difference(P0.05).Histological slices in the experimental group showed that the absorption,organization of hematoma,the formation of trabeculae and matrix preceded those in the control group.There were more fibroblast,osteoblasts and callus in the experimental group.[Conclusion]Cell-scaffold complex composed with BMCs and ?-TCP stimulated by LIPUS can repair bone defect more effectively than that without LIPUS stimulation at the early stage of healing,but the effect tend to decrease at the late stage.

Objective To study the influence of Langchuang Ⅱ,a Chinese medicinal compound formula,on Th1/TH2cytokines of MRL/lpr lupus mice.Methods Forty MRL/lpr mice with spontaneous systemic lupus erythematosus(SLE) were randomized into blank control group,LangchuangⅡgroup(in the dose of 20 g?kg-1?d-1),prednisone group(in the dose of 6 mg?kg-1?d-1),and the combination group(LangchuangⅡand prednisone).After medication for 8 continuous weeks,Flowcytomix technology was used for the detection of different kinds of serum Th1/Th2 cytokines.Results Compared with the blank control group,serum granulocyte-macrophage colony-forming unit(GM-CSF) level was decreased in the combination group(P0.05);IL-4,IL-5 and IL-10 were all decreaed in the medication groups,and the decrease of IL-10 was obvious in the combination group(P

OBJECTIVE To discover a small-molecule bromodomain-containing protein 4 (BRD4) inhibitor that induces AMP- activated protein kinase- modulated autophagy- associated cell death in breast cancer and exploreits potential mechanisms. METHODS BRD4 interactors were analyzed by PPI network prediction and The Cancer Genome Atlas (TCGA) analysis. The interaction between BRD4 and AMPK was confirmed by co- immunoprecipitation assay. Novel BRD4 inhibitors were designed and synthesized based upon pharmacophore analysis of BRD4 (1), then screened by anti-proliferative activity and Alpha Screen of BRD4 (1). The selectivity of the best candidate compound 8f was validated by co-crystallization, FRET assay and co-immuno precipitation assay. The mechanisms of 8f were investigated by fluorescence microscopy, electron microscopy, Western blotting, immunocy?tochemistry, siRNA and GFP-mRFP-LC3 plasmid transfections, as well as immunohistochemistry and immunofluorescence. Potential mechanisms were discovered by iTRAQ- based proteomics analysis and the therapeutic effect of 8f was assessed by xenograft breast cancer mouse and zebrafish models. RESULTS We identified that BRD4 interacted with AMPK, which was remarkably downregulated in breast cancer. We next designed and synthesized 49 candidate compounds, and eventually discovered a selective small-molecule inhibitor of BRD4 (8f). Subsequently, 8f was discovered to induce autophagy-associated cell death (ACD) by BRD4- AMPK interaction, and thus activating AMPK- mTOR- ULK1-modulated autophagic pathway in breast cancer cells. Interestingly, the iTRAQ- based proteomics analyses revealed that 8f induced ACD pathways, involved in HMGB1, VDAC1/2 and eEF2. Moreover, 8f displayed a therapeutic potential on both xenograft breast cancer mouse and zebrafish models. CONCLUSION We discovered a novel small-molecule inhibitor of BRD4 that induces BRD4-AMPK-modulated ACD in breast cancer, which may provide a candidate drug for future cancer therapy.

Objective: To study the changes of andrographolides in the drying process of the extract of Andrographis paniculata Nees. Methods: HPLC method was applied to analyze andrographolide and 14 deoxy 11, 12 didehydroandrographolide in the process. Results: The content of andrographolide descended rapidly in the whole drying process, while the content of 14 deoxy 11, 12 didehydroandrographolide ascended at first 12 hours, declined in content was slowly to follow. Conclusion: Baking temperature is not the only main factor to stimulate the transformation of andrographolide and 14 deoxy 11, 12 didehydroandrographolide.

Objective To determine the optimum dose of bupivacaine for spinal anesthesia with epidural volume extension (EVE) in patients undergoing cesarean delivery.Methods A total of 100 parturients,weighing 55-100 kg,with body height of 155-170 cm,of American Society of Anesthesiologists physical status Ⅰ or Ⅱ,scheduled for elective cesarean delivery,were included and randomized to receive bupivacaine at 5 different doses (A,B,C,D,and E groups) using a random number table,with 20 patients in each group.In A,B,C,D,and E groups,bupivacaine 6.75,7.50,8.25,9.00 and 9.75 mg were injected into the subarachnoid space,respectively,and the volume was all 1.5 ml.After successful spinal anesthesia,an epidural catheter was placed,and normal saline 10 ml was given through the catheter to perform EVE.A successful spinal block was defined as attainment of sensory block of at least T5 within 15 min after EVE along without requirement for additional local anesthetics within 60 min after EVE.The rate of successful spinal anesthesia,time to reach sensory block of T5,the maximum level of sensory block,and the first requirement for local anesthetics were recorded.The occurrence of hypotension,tachycardia,bradycardia,nausea,vomiting,chest distress,dyspnea,shivering,and referred pain and consumption of metaraminol were recorded during spinal anesthesia.Apgar scores at 1 and 5 min after birth were recorded.Results With the increasing doses of bupivacaine,the efficacy of spinal anesthesia was enhanced,and the occurrence of adverse reactions was increased.Compared with group C,the rate of successful spinal anesthesia,and the maximum level of sensory block were significantly increased,the time to reach sensory block of T5 was shortened,and the incidence of hypotension and nausea and consumption of metaraminol were increased in group E;the time to reach sensory block of T5 was significantly shortened,Apgar scores at 1 min after birth were increased (P＜0.05),and no significant change was found in the rate of successful spinal anesthesia,the first requirement for local anesthetics,the rate of time to reach sensory block ofT5≤ 15 min,and the maximum level of sensory block in group D (P＞0.05).Compared with group D,the time to reach sensory block of T5 was significantly shortened,the incidence of nausea and consumption of metaraminol were increased (P＜0.05),and no significant change was detected in the rate of successful spinal anesthesia,the first requirement for local anesthetics,the rate of time to reach sensory block of T5 ≤ 15 min,and the maximum level of sensory block in group E (P＞0.05).Conclusion The optimum dose of bupivacaine for spinal anesthesia with EVE is 9.00 mg in patients undergoing caesarean delivery.

Objective To investigate the effect of local application of triamcinolone acetonide in promoting wound healing and recurrence after granulomatous lobular mastitis (GLM) operation. Methods The clinical data of 55 GLM patients with the diameter > 5 cm were retrospectively analyzed, and all patients treated with incision drainage to breast abscess and removal of inflammatory lesions. Thirty - one patients were treated with routine dressing change after operation (control group), and 24 patients were treated with routine dressing change and triamcinolone acetonide injection after operation (experiment group). The wound dressing time, recovery rate and recurrence rate were compared between 2 groups, and hormone related adverse reaction of experiment group was observed. Results The wound dressing time in experiment group was significantly shorter than that in control group:(58 ± 19) d vs. (71 ±25) d, and there was statistical difference (P<0.05). There were no statistical differences in the recovery rate and recurrence rate between experiment group and control group:91.7%(22/24) vs. 83.9%(26/31) and 9.1%(2/22) vs. 15.4% (4/26), P>0.05. The patients of experiment group did not have the hormone related adverse reaction. Conclusions The local application of triamcinolone acetonide after GLM operation can accelerate the wound healing, and it may also contribute to higher recovery rate and lower recurrence rate.