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 determine non-thermal biological effect of low frequency pulsed electromagnetic field (LFPEF)on the stomach blood circulation and ultra microstructure of rat stress ulcer. Methods Thirty-six Sprague-Dawley rats were assigned to three equal groups:control,ulcer without interference group(UW)and ulcer exposure groups(UE).The rats stress ulcer models were constructed with the combination method of soak and bind in the low-pressure and hypoxia circumstance. Based on the singlechip,a LFPEF generator with adjustable frequency, amplitude and duty ratio was developed. Then the stomachs of the rats were exposed to the LFPEF generator 3 hours per day.On days 1,3,5 and 7,the blood circulation of the stomach was analyzed by the content of the serum NO and contrast ultrasonography.In addition,the ulcer tissue was taken out for section-staining. Finally, the pathological change of the stomach ultra microstructure was observed under a light microscope. Results On different days, the contents of the serum NO and microbubble concentration of UE group were significantly higher than those of the UW group(P<0.05). The pathological observation showed that the restoration of the gastric tissue in UE group was faster than that in the UW group(P<0.05).Conclusion LFPEF with certain proper parameter could improve the gastric tissue blood circulation and accelerate the stress ulcer restoration. [Chinese Medical Equipment Journal,2018,39(5):35-38]

The structure analysis of porcine hemoglobin alphabeta dimer and the calculation of solvent accessible surface of the amino acids showed the epsilon-amino groups of the lysine are suitable for modification by polyethylene glycol (PEG). The modification of the lysine residues will not affect the carring oxygen capacity of Hb. Three types of linker have been designed to connect PEG and porcine hemoglobin. The lysines between porcine and bovine hemoglobin (pHb and bHb) are highly conserved, but the solvent accessible surface of conserved lysines are different. These suggested that the properties of homologous proteins are similar in pHb and bHb, but the characteristic derived from the homology analysis will be deviated from the actual status. The results of molecular dynamics simulation suggested that the chemical modified porcine hemoglobin would be no immunogenicity.

OBJECTIVE: To explore the obesity distribution in old people and the relation between senile obesity and health. METHODS: First, a questionnaire was designed which included chronic disease history, body mass index (BMI), physiological value, biochemistry index, anti-oxidation index, diagnosis of diseases, etc. Second, the measure and detection methods were unified; and the last, the investigation was made along with daily clinical work by clinicians. RESULTS: We received 391 questionnaires. The overweight rate was 36.1% and the obesity rate was 7.9% . Total anti-oxidation activity in serum (TAS) and superoxide dismutase (SOD) decreased with body mass index (BMI), and the value in the obesity group was the lowest; Malonaldehyde (MDA) of overweight obesity was the largest. The mean blood pressure, blood fat, and blood glucose as well as the prevalence of cardiovascular disease, hyperlipemia, and glycuresis increased with BMI; and the value in the obesity group was the largest. CONCLUSION The prevalence of the senile obesity was below the average and the senile obesity complications were various and serious, and perhaps related to imbalance of free radical's production and cleanup, so the senile obesity seriously harmed old people's health.
Aged ; Body Mass Index ; Cardiovascular Diseases ; epidemiology ; etiology ; Cerebrovascular Disorders ; epidemiology ; etiology ; China ; epidemiology ; Female ; Humans ; Male ; Middle Aged ; Obesity ; complications ; epidemiology ; Overweight ; Prevalence ; Risk Factors

BACKGROUNDAssessing the radiographic features of knee osteoarthritis (OA), especially joint space narrowing, is important for evaluating disease progression. The purpose of this study was to quantitatively analyze joint space narrowing by measuring 2 new variables: the average joint space width (aJSW) and the articulate angle (AA) on X-ray films, and to evaluate the relationship between the 2 variables, knee function and OA symptoms.

METHODSUsing the web-based radiology viewer (Cedara I-Reach™ 4.1.1), we measured the 2 variables in 50 knees of 41 patients with knee OA participating in the Shanghai OA Study. We also evaluated the Kellgren-Lawrence (K-L) grade, the Western Ontario and McMaster Universities OA Index (WOMAC), and additional questionnaire in OA knees. The study was approved by the ethics committee of Shanghai Ninth People's Hospital (No. 2009 - 28).

RESULTSThe aJSW correlated with the K-L grade (r = -0.57, P < 0.001), kneeling (r = -0.29, P = 0.04), sitting cross-legged on the floor (r = -0.31, P = 0.03), WOMAC pain (r = -0.31, P = 0.03), WOMAC disability (r = -0.35, P = 0.01), pain while squatting (r = -0.37, P = 0.01), and defecating in a squatting position (r = -0.39, P = 0.01). The AA correlated with defecating in a squatting position (r = 0.29, P = 0.05), WOMAC disability (r = 0.30, P = 0.04) and K-L grade (r = 0.44, P = 0.003). The K-L grade also correlated with pain while squatting (r = -0.40, P = 0.005) and defecating in a squatting position (r = -0.34, P = 0.02), WOMAC pain (r = 0.30, P = 0.04), and WOMAC disability (r = 0.30, P = 0.04).

CONCLUSIONSThe aJSW closely correlated with knee OA symptoms and function scores, and was more sensitive to knee OA related disabilities than K-L grade and the AA. The aJSW could be used as a new variable for knee OA evaluation.

Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Knee Joint ; diagnostic imaging ; physiopathology ; Male ; Middle Aged ; Osteoarthritis, Knee ; diagnostic imaging ; physiopathology ; Pain Measurement ; Radiography

TLR2 activity plays an important role in the pathogenesis of autoimmune diseases, tumor carcinogenesis and cardio-cerebrovascular diseases. To establish a TLR2 receptor-based cell screening model, NF-kappaB promoter-driven luciferase reporter plasmids were transfected into human embryonic kidney cells (HEK293) stably expressing human TLR2 and co-receptors CD14, TLR1 and TLR6. Single clones were then isolated and characterized. Using this screening system, a human TLR2-binding peptide C8 was obtained from the Ph.D.-7 Phage Display Peptide Library through biopanning and rapid analysis of selective interactive ligands (BRASIL). The binding characteristic of C8 with human TLR2 was evaluated by ELISA, flow cytometry and immunofluorescence. The NF-kappaB luciferase activity assay showed that C8 could activate the TLR2/TLR1 signaling pathway and induce the production of cytokines TNF-alpha and IL-6. In conclusion, the TLR2 receptor-based cell screening system is successfully established and a new TLR2-binding peptide is identified by using this system.
Bacteriophages ; Drug Evaluation, Preclinical ; Genes, Reporter ; HEK293 Cells ; Humans ; Interleukin-6 ; metabolism ; Lipopolysaccharide Receptors ; metabolism ; Luciferases ; genetics ; metabolism ; Peptide Library ; Peptides ; metabolism ; pharmacology ; Promoter Regions, Genetic ; Protein Binding ; Signal Transduction ; drug effects ; Toll-Like Receptor 1 ; metabolism ; Toll-Like Receptor 2 ; metabolism ; Toll-Like Receptor 6 ; metabolism ; Transfection ; Tumor Necrosis Factor-alpha ; metabolism

Background: and Purpose Orthostatic hypotension (OH) is common in patients with Parkinson’s disease (PD). Early recognition OH is required with sensitive assessments. The purpose of this study was to determine whether blood pressure (BP) changes during exercise can predict the occurrence of OH in PD. Methods: This prospective cohort study included 80 consecutive patients with PD. All patients agreed to participate in a baseline evaluation and cardiopulmonary exercise test (CPET).According to the initial active standing test (AST), those without OH (PD-nonOH) at baseline had their AST results followed up for 6 months. The main outcome was defined as whether patients without OH at baseline would develop OH after 6 months. Logistic regression analysis was applied to identify the relevant variables. A nomogram was constructed based on clinical features and identified variables. The concordance index (C-index) and area under the receiver operating characteristic curve (AUC) were used to evaluate the accuracy and predictive ability of the nomogram, respectively. Results: CPET results indicated that peak load, peak heart rate, heart rate recovery at 1 min, and systolic BP change (ΔSBP) were lower in those with OH than in the PD-nonOH group (p<0.05) at baseline. Logistic regression analysis indicated that peak load and ΔSBP during CPET had significant effects on OH (p<0.05). Age, sex, peak load, and ΔSBP were used to construct the nomogram model (C-index=0.761). The prediction model had an AUC of 0.782 (95% confidence interval=0.649–0.889) and a specificity and sensitivity of 70.0% and 81.8%, respectively. Conclusions This study has identified predictive factors for OH development in patients with PD. CPET could be used as a complementary examination to identify patients at a high risk of OH.

Kallmann syndrome (KS) is a rare pediatric disease with major manifestations of olfactory dysfunction and hypogonadotropic hypogonadism. Five children (4 boys and 1 girl) with KS reported in this article were aged between 6 months and 19 years at the time when they attended the hospital. All the children had the clinical manifestation of hypogonadotropic hypogonadism; in addition, three children had olfactory dysfunction (two were found to have olfactory bulb dysplasia on magnetic resonance imaging), one had cleft lip and palate, and one had micropenis and cryptorchidism with right renal agenesis during infancy. All the five children had normal karyotype and their parents had normal clinical phenotypes. The uncle of one child had underdeveloped secondary sexual characteristics and olfactory disorder since childhood. High-throughput sequencing found two known heterozygous missense mutations in the FGFR1 gene, i.e., c.1097C>T(p.P366L) and c.809G>C(p.G270A), in two children. One child had a novel frameshift mutation, c.1877_1887/p.S627Tfs*6, in the KAL1 gene; this deletion mutation caused a frameshift in base sequence and produced truncated proteins, which led to a significant change in protein structure, and thus it was highly pathogenic. It is concluded that KS has great clinical and genetic heterogeneity and can be accompanied by incomplete dominant inheritance and that gene detection helps with the diagnosis of this disease.
Adolescent ; Child ; Child, Preschool ; DNA Mutational Analysis ; Extracellular Matrix Proteins ; Female ; Heterozygote ; Humans ; Hypogonadism ; Infant ; Kallmann Syndrome ; Male ; Mutation ; Nerve Tissue Proteins ; Receptor, Fibroblast Growth Factor, Type 1 ; Young Adult

OBJECTIVE: To assess the performance of a high-definition CT (HDCT) for imaging small caliber coronary stents (< or = 3 mm) by comparing different scan modes of a conventional 64-row standard-definition CT (SDCT). MATERIALS AND METHODS: A cardiac phantom with twelve stents (2.5 mm and 3.0 mm in diameter) was scanned by HDCT and SDCT. The scan modes were retrospective electrocardiography (ECG)-gated helical and prospective ECG-triggered axial with tube voltages of 120 kVp and 100 kVp, respectively. The inner stent diameters (ISD) and the in-stent attenuation value (AVin-stent) and the in-vessel extra-stent attenuation value (AVin-vessel) were measured by two observers. The artificial lumen narrowing (ALN = [ISD - ISDmeasured]/ISD) and artificial attenuation increase between in-stent and in-vessel (AAI = AVin-stent - AVin-vessel) were calculated. All data was analyzed by intraclass correlation and ANOVA-test. RESULTS: The correlation coefficient of ISD, AVin-vessel and AVin-stent between the two observers was good. The ALNs of HDCT were statistically lower than that of SDCT (30 +/- 5.7% versus 35 +/- 5.4%, p < 0.05). HDCT had statistically lower AAI values than SDCT (15.7 +/- 81.4 HU versus 71.4 +/- 90.5 HU, p < 0.05). The prospective axial dataset demonstrated smaller ALN than the retrospective helical dataset on both HDCT and SDCT (p < 0.05). Additionally, there were no differences in ALN between the 120 kVp and 100 kVp tube voltages on HDCT (p = 0.05). CONCLUSION: High-definition CT helps improve measurement accuracy for imaging coronary stents compared to SDCT. HDCT with 100 kVp and the prospective ECG-triggered axial technique, with a lower radiation dose than 120 kVp application, may be advantageous in evaluating coronary stents with smaller calibers (< or = 3 mm).
Analysis of Variance ; Cardiac-Gated Imaging Techniques/methods ; Coronary Disease/*radiography/*therapy ; Humans ; Phantoms, Imaging ; Radiation Dosage ; Radiographic Image Interpretation, Computer-Assisted ; *Stents ; Tomography, Spiral Computed/*methods

OBJECTIVESKnee osteoarthritis (OA) is a major cause of pain and functional limitation. Short-term Baduanjin () exercise had been testified to be beneficial to the disease. This study conducted an initial assessment of the one-year Baduanjin exercise on knee OA.

METHODSThe recruited patients practiced Baduanjin at the community recreational center. Sessions were held for 30 min five times a week for one year. Knee pain, stiffness, physical disability, general health, knee extensors and flexors strength, and aerobic ability were measured using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the Medical Outcomes Study Short Form-36 (SF-36), the 6-Minute Walk Test (6-MWT), and the Isokinetic Strength of the Knee Extensors and Flexors (ISKEF). Body mass index (BMI) was also calculated before and after the study period for comparison.

RESULTSTwenty-eight patients signed the informed consent. Six patients withdrew from the trial. Twenty-two patients (29 knees) completed the one-year study. After one-year Baduanjin exercise, WOMAC pain (132.0±69.6 vs. 56.2±67.6, P=0.000), stiffness (64.7±54.8 vs. 22.3±34.6, P=0.000), and physical function subscales (386.1±275.8 vs. 182.0±235.7, P=0.003); SF-36 body pain (45.7±20.0 vs. 57.4±17.9, P=0.005), general health (50.5±20.0 vs. 62.1±16.1, P=0.004), role emotional (64.4±26.1 vs. 73.5±21.3, P=0.047), and health transition (3.3±1.0 vs. 2.6±1.0, P=0.008); BMI (25.0±2.9 vs. 24.4±2.9, P=0.032); 6-MWT (565.7±94.6 vs. 610.5±66.7, P=0.036); and ISKEF Peak Torque (the Knee Extensors: 60.5±25.5 vs. 76.8±31, P=0.000; the Knee Flexors: 29.3±15.9 vs. 37.1±15.8, P=0.001) were significantly improved. No adverse effects resulted from the exercise.

CONCLUSIONSIt suggested that the long-term Baduanjin could be a feasible and safe exercise option for knee OA.

Aged ; Aged, 80 and over ; Exercise Therapy ; Female ; Humans ; Male ; Middle Aged ; Osteoarthritis, Knee ; therapy