Autophagy is an important homeostatic cellular recycling mechanism responsible for degrading injured or dysfunctional cellular organelles and proteins in all living cells. Aging is a universal phenomenon characterized by progressive deterioration of cells and organs due to accumulation of macromolecular and organelle damage. Growing evidences indicate that the rate of autophagosome formation and maturation and the efficiency of autophagosome/lysosome fusion decline with age. Dysfunctional autophagy has also been observed in age-related diseases. Autophagy disruption resulted accumulation of mutated or misfolded proteins is the essential feature of neurodegenerative disorders. However, in cancers, fibroproliferative diseases or cardiovascular diseases, autophagy can play either a protective or destructive role in different types of disease, and even in different stages of the same disease. The review will discuss the cellular and molecular mechanisms of autophagy and its important role in the pathogenesis of aging and age-related diseases, and the ongoing drug discovery strategies for therapeutic intervention.
Aging ; Autophagy ; Drug Discovery ; Humans ; Lysosomes ; metabolism ; Neurodegenerative Diseases ; Phagosomes ; metabolism ; Protein Folding

Objective To evaluate the relationship between the mechanism of spinal monocyte chemoattractant protein-1 (MCP-1)-mediated maintenance of chronic pathological pain and synaptic transmission in spinal dorsal horns of rats.Methods Female Sprague-Dawley rats,aged 2-3 weeks after birth,weighing 150-210 g,were studied.The experiment was performed in 2 parts.Experiment Ⅰ Eighteen Sprague-Dawley rats were randomly divided into 2 groups (n =9 each) on 7 days after intrathecal catheters were inserted:phosphate buffer solution (PBS) group and MCP-1 group.PBS 10 μl was intrathecally injected in group PBS,and PBS 10 μ1 containing 100 ng MCP-1 was intrathecally injected in group MCP-1.The mechanical pain threshold was measured at 30 and 60 min before intrathecal injection,and 30,60,90,120,150 and 180 min and 1,2 and 3 days after intrathecal injection.Experiment Ⅱ The transverse spinal cord slices were prepared,and substantia gelatinosa neurons were selected for whole-cell patch-clamp recording.Electrophysiological recording was performed at 1 h of incubation with artificial cerebrospinal fluid (ACSF) and immediately after adding MCP-1:for excitatory synaptic transmission recording,MCP-1 (final concentration 100 nmol/L),N-methyl-D-aspartate (NMDA,final concentration 100 μmol/L) and α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA,final concentration 20 μmol/L) were added to ACSF,and spontaneous excitatory postsynaptic currents (sEPSCs),AMPA receptors-mediated currents and NMDA receptors-mediated currents were recorded;for inhibitory synaptic transmission recording,MCP-1 (final concentration 100 nmol/L) and γ-aminobutyric acid (GABA,final concentration 1 mmol/L) were added to ACSF,and spontaneous inhibitory postsynaptic currents (sIPSCs) and GABA receptors-mediated currents were recorded.Results Compared with group PBS,the mechanical pain threshold was significantly decreased at 30 min-2 days after intrathecal injection in group MCP-1 (P＜0.01).Compared with those at 1 h of incubation with ACSF,the frequency and amplitude of sEPSCs were significantly increased,the amplitude of NMDA receptors-and AMPA receptors-mediated currents were increased,the frequency and amplitude of sIPSCs were decreased,and the amplitude of GABA receptors-mediated currents was decreased immediately after adding MCP-1 (P＜0.05).Conclusion MCP-1 enhances excitatory synaptic transmission through enhancing the function of NMDA and AMPA receptors in the posterior substantia gelatinosa neurons of the spinal cord;MCP-1 weakens inhibitory synaptic transmission through inhibiting GABA receptor function,which may be involved in MCP-l-mediated maintenance of chronic pathological pain in rats.

Objective To investigate the influence of all-round intervention on the quality of life and the emotion of cancer patients who have accepted the gamma knife therapy. Method Using health education, psychotherapy and the behavior treatment for 260 patients with malignant tumor who had accepted the gamma knife therapy. Evaluated the quality of life and the emotion of these patients before and after the intervention respectively by using questionnaire of QOL, SCL-90, SDS and SAS. Results The values of indicated the QOL, SCL-90, SDS and SAS before the all-round intervention were 23.12?4.68, 68.12?33.26, 40.12?10.28 and 42.48?12.16 respectively. The values which had obtained after the all-round intervention were 46.26?3.28, 36.12?26.23, 28.16?5.23 and 26.12 ?10.66 respectively, there were significant differences between them,P

The phenomena of attention economyand influence economypresented in news media also applies to medical library.Proposed in this paper are the ways and measures for medical libraries to realize their influence economybased on the analysis of their attention economy.

Objective To investigate the clinical efficacy of endovascular treatment for iliac vein compression syndrome (IVCS) in 112 cases. Methods From September 2011 to June 2015, 112 cases of IVCS (Cockett syndrome) were treated in our hospital with endovascular methods .The case numbers of different CEAP ( clinical etiological anatomical pathophysical ) classifications were C2 (45 cases), C3 (23 cases), C4 (19 cases), C5 (11 cases) and C6 (14 cases).All the cases were diagnosed by venography .The operations started from puncturing the ipsilateral veins .The stenotic degree and compressed intensity of iliac vein were evaluated by the minimum diameter with low pressure balloon .And then a stent was placed into after percutaneous transluminal angioplasty ( PTA) when residual stenosis was more than 50%.The occlusive segment was dilated by 8 mm diameter balloon firstly , and catheter directed thrombolysis treatment was applied if thrombus was detected .The PTA and stenting were performed when the thrombus was completely removed .The improvement of clinical symptoms was observed after operation and the patients were followed up by ultrasound and venograghy . Results Nine cases were given PTA only , and the other 103 cases underwent stent placement . Postoperative venography showed collateral vessels were disappeared in 22 cases, obviously decreased in 56 cases and mildly decreased in 34 cases.The average difference of swelling leg ’s circle was diminished from (2.56 ±0.88) cm pre-operation to (0.93 ±0.71) cm post-operation, while the average area of skin ulcer was diminished from (6.34 ±3.78) cm2 pre-operation to (2.13 ±1.88) cm2 post-operation, all of which were statistically significant (t =20.24 and 7.19,P=0.000).A total of 86 cases were successfully followed up during a period from 2 months to 45 months (average, 19.2 months).The patency rate of treated iliac vein 12 months after operation was 76.2%in the PTA group, and in the PTA with stenting group was 96.7%, 88.6%, and 86.1%, respectively, at 12, 24, and 36 months after operation, in which a statistical significance was detected (log-rank χ2 =30.32, P=0.000).The patency rate in diameter ≥16 mm group was 95.2%and 95.2%, respectively, at 12 and 24 months after operation, while in diameter <16 mm group was 97.0%and 93.3%, respectively, in which no statistical significance was detected (log-rankχ2 =0.39, P=0.532).Thrombotic complication was found in 2 cases during the follow-up period , including 1 case of iliac vein thrombosis at 1 month and 1 case of thrombus in contralateral leg 8 months later .According to the results of venography in 78 cases at 12 months after operation , restenosis was found in 5 out of 6 cases in the PTA group, and the patency rate in the stent placement group was 95.8%(69/72).No stent migration was found . Conclusion Comfortable clinical results were obtained after endovascular therapy for iliac vein compression syndrome , and the application of stenting could increase the middle and long term patency rate of treated vessels .

Objective To evaluate the effects of hydrogen-rich saline on the early diabetic neuropathic pain (DPN) in rats.Methods Healthy male Sprague-Dawley rats,aged 8 weeks,weighing 180-220 g,were used in the study.DPN model was made by intraperitoneal injection of 1％ streptozocin (STZ) 65 mg/kg.Twelve diabetic rats were randomly divided into 2 groups (n =6 each) using a random number table:DPN group and hydrogen-rich saline group (HRS group).Another 6 normal rats were randomly collected as control group (group C).At 14 days after STZ injection,hydrogen-rich saline 5 ml/kg was injected intraperitoneally once a day for 14 consecutive days in HRS group,while C and DNP groups received the equal volume of normal saline.Mechanical paw withdrawal threshold to yon Frey stimuli (MWT) and paw withdrawal latency to nociceptive thermal stimulation (TWL) were measured at 2 days before STZ injection (To) and 7,14,21 and 28 days after STZ injection (T1-4).The motor nerve conduction velocity (MNCV) of the right hindlimb and distal motor latency was measured after pain threshold was measured at T4.After measurement of neurological function was completed,tumor necrosis factor-α (TNF-α) and i nterleukin-6 (IL-6) contents (by ELISA) and nuclear factor kappa B (NF-κB) activity (by immuno-histochemistry) were detected.Results Compared with group C,MNCV was significantly decreased,the motor latency was prolonged,MWT was decreased at T1-T4,TWL was shortened at T2-T4,TNF-a and IL-6 contents were increased,and NF-κB activity was enhanced in DNP and HRS groups (P ＜ 0.05).Compared with group DNP,MNCV was significandy increased,the motor latency was shortened,MWT was increased at T3.4,TWL was prolonged at T4,TNF-a and IL-6 contents were decreased,and NF-κB activity was weakened in group HRS (P ＜ 0.05).Conclusion Hydrogen-rich saline can relieve the early DPN through inhibiting NF-κB signaling pathway in rats.

Objective • To estimate the reliability and validity of Beck Depression Inventory (BDI), Self-rating Depression Scale (SDS) and Center for Epidemiologic Studies Depression Scale (CES-D) that used for systemic lupus erythematosus (SLE) to choose a more suitable depression scale, and analyze the risk factors for depression in SLE. Methods • A total of 259 questionnaires were completed by SLE patients with their informed consent in the early stage. Internal consistency, test-retest reliability, construct validity, consistency and correlation of depression outcomes were analyzed. The most suitable scale was used in 70 SLE patients. The results of depression screening and clinical information were collected to analyze the risk factors for SLE with depression. Results • A total of 240 valid questionnaires were collected. The Cronbach's α coefficients of BDI, SDS, and CES-D were 0.899, 0.884, and 0.711, respectively. The total scores of the three scales were correlated with every item (P<0.05). The test-retest coefficients of BDI, SDS, and CES-D were 0.912, 0.635, and 0.728, respectively (P<0.01). The result of validity analysis showed that the KMO (Kaiser-Meyer-Olkin) values of BDI, SDS, and CES-D were 0.888, 0.895, and 0.918, respectively. The total variation of main factor interpretation of BDI, SDS, and CES-D was 63.13%, 57.09%, and 57.89%, respectively. The results of BDI showed 117 patients (48.25%) with depression, while SDS showed 154 patients (64.16%) with depression and CES-D showed 140 patients (58.33%) with depression. The correlation coefficients of the three scales were 0.939-0.971 (P<0.01). κ Values of all three scales were greater than 0.4 (P<0.01). Younger than 30, unemployment and renal involvement were independent risk factors for SLE with depression. Conclusion • With better internal consistency, test-retest coefficients, good brief framework and well-understood items, BDI seems to be a more suitable scale for SLE. Unemployed, renal involved and young SLE patients are more likely to suffer from depression.

Objective Toexploretheclinicalefficacyandtoxicityofintensitymodulatedradiationtherapy(IMRT)combined with high intensity focused ultrasound(HIFU) for inoperatable recurrent hepatic carcinoma after operation and TACE .Methods Total 60 patients with inoperatable recurrent hepatic carcinoma after operation and TACE were randomly divided into two group ,30 patients in observation group received IMRT and HIFU ,while 30 patients in control group received only IMRT .For both groups , the same radiotherapy technic was given with IMRT in 6 MV X‐ray ,the total dose was 54 -70 Gy/6 -7 weeks .In observation group ,HIFU was carried out concurrently with IMRT (5 days/week ,6-7 weeks) .Results The difference of the short‐term effi‐cacy between the observation group and the control group was statistically significant (P<0 .05) ,there was no significant difference in acute radioactive toxicity between the two groups (P>0 .05) .The one and two year overall survival rate 89 .9% ,78 .9% in obser‐vation group ,while 72 .8% ,36 .2% in control group ,the differnces were statistically significant (P<0 .05);the one and two year progression‐free survival rate were 85 .9% and 50 .9% in observation group ,while 64 .3% and 28 .1% in control group ,the differ‐ences between two groups were statistically significant (P<0 .05) .The medium survival time was 36 months in observation group , and 24 months in control group;the medium progression‐free survival was 27 months in observation group ,and 17 months in control group .Conclusion For recurrent unresectable or reject surgery after TACE in patients with primary hepatic carcinoma ,the efficacy of IMRT combined with HIFU treatment is effective ,the toxicity can be tolerated ,and has certain application value .

Aged ; Anthracosis ; physiopathology ; Humans ; Lung ; physiopathology ; Male ; Middle Aged ; Pulmonary Ventilation ; Respiratory Function Tests

Humans ; Liver Abscess