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 quantitatively evaluate the left ventricular systolic synchrony in patients with chronic renal failure (CRF) by real-time three-dimensional echocardiography (RT-3DE). Methods Thirty patients with CRF and twenty-five normal subjects were enrolled in this study.The M-mode ejection fraction (M-EF), left ventricular end diastolic internal diameter (LVIDd), interventricular septum diameter (IVSd), left ventricular posterior wall diameter (LVPWd) were obtained on two-dimension. The global and regional volume-time curves were obtained on three -dimensional. The end diastolic volume (LVEDV),end systolic volume (LVESV) and ejection fraction (LVEF) of left ventricule, the time to minimal systolic volume (Tmsv) of 16,12,6-segmental standard deviation (Tmsv16, 12, 6-SD), maximal difference (Tmsv16, 12, 6-Dif) were derived from Qlab software . The above parameters as a percentage of the cardiac cycle with different heart rates between patients were also calculated from the Qlab software, which were Tmsv16, 12, 6-SD% and Tmsv16, 12, 6-Dif %, rspectively. Results The indices of HR, LVIDd, IVSd, LVPWd and LVESV were significantly higher while LVEF was significantly lower in the CRF group than those of the control group (P<0.05 or P<0.01); The indices of systolic asynchrony of Tmsv16,12-SD%, Tmsv16,12-Dif, Tmsv16 ,12 ,6-SD/R-R%,Tmsv16,12,6-Dif/R-R% were significantly larger in the CRF group than those of the control group(P<0.05 or P<0.01). Conclusions RT-3DE provides a simple, intuitional and noninvasive approach to assess the systolic synchrony of all the LV segments simultaneously and LVEF in patients with chronic renal failure.

The nuclear transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) plays a crucial role in maintaining cellular redox homeostasis. The aberrant NRF2 signaling confers enhanced antioxidant capacity, which is linked to tumor progression and therapeutic resistance. The current study investigates the biological effects and molecular mechanism of tribbles homolog 3 (TRIB3), a stress-induced protein, in regulating cell survival and apoptosis in lung cancer. This study first performed the RNA sequencing data analysis with 576 lung adenocarcinoma patients from the cancer genome atlas (TCGA) database. The NRF2- antioxidant response element (ARE) signature was enriched in patients with high TRIB3 expression. Dual-luciferase reporter assay and real-time quantitative polymerase chain reaction (PCR) were used to confirm the effect of TRIB3 on the kelch-like ECH-associated protein-1 (KEAP1)-NRF2 pathway. Abrogation of TRIB3 impaired NRF2 transcriptional activity and reduced the expression of its target genes. Moreover, TRIB3 enhanced NRF2 stability via blocking KEAP1-NRF2 interaction. TRIB3-depletion promoted reactive oxygen species (ROS) production, restrained cell proliferation, and enhanced carboplatin-induced apoptosis. In addition, NRF2 overexpression recovered the tumor inhibition effect of TRIB3-depletion. Consistently, TRIB3 failed to modulate apoptosis in NRF2 depletion cells. In summary, this study shows that TRIB3 inhibits the KEAP1-NRF2 interaction and upregulates the transcriptional activity of NRF2, thereby promoting lung cancer cell proliferation and reducing the sensitivity to chemotherapy. Targeting the TRIB3-NRF2 signal axis may become a new strategy for ROS homeostasis and lung cancer treatment.

Objective To study the bacterial types and their drug resistance in intra-abdominal infections after pancreatic surgery,and to evaluate the appropriate treatment measures.Methods 113 patients who underwent pancreatic surgery from Jan 2012 to Dec 2012 in our hospital were included into this study.The drainage liquid from the surgical sites were collected for bacterial culture and drug susceptibility tests.Results The incidence of intra-abdominal infections was 39.8％ (45/113).There were 54 pathogenic strains of bacteria isolated,including 49 strains of gram-negative bacteria (90.7％),4 strains of gram-positive bacteria (7.4％),and 1 strain of fungus (1.9％).The top three pathogens were Pseudomonas aeruginosa (50.0％),Acinetobacter baumannii (14.8％) and Singular deformation bacteria (1 1.1％).Most gram-negative bacteria were sensitive to Polymyxin B and Aminoglycoside antibiotics (＞ 70％),but they were resistant to Imipenem and Cephalosporin which were commonly administered.Pancreatic fistula was closely related to intra-abdominal infections.Concluusions A gram-negative bacteria,Pseudomonas aeruginosa,was the predominant organism in intra-abdominal infections after pancreatic surgery in our hospital.The situation of drug-resistance was still severe.More effective measures should be taken to prevent growth of resistant strains such as using antibiotics according to drug sensitivity and avoiding empirical single use of broad-spectrum antibiotics.Pancreatic fistula commonly led to intra-abdominal infections.

AIM: To evaluate the changes of corneal high - order aberration (including Coma, Spab, RMSh) after laser in situ keratomileusis (LASIK) with femtosecond laser, sub- Bowman keratomileusis ( SBK ) and laser epithelial keratomileusis (LASEK). METHODS: Of 82 myopic patients ( 164 eyes ), 31 patients (62 eyes) were treated by FS-LASIK, 31 patients (62 eyes) were treated by SBK, 20 patients (40 eyes) were treated by LASEK. Sirius system was used for measuring the coma aberration, spherical aberration, and high order aberration at 1, 15d,1, 3mo after surgery. RESULTS: 1) Vision: The uncorrected visual acuity of the three groups had no differences (P>0. 05). 2) Corneal aberrations: Three kinds of surgical procedure for patients with corneal aberration had significant impact. The C7, C8, C12 and RMSh of three groups were increased significantly (P<0. 05). The C7, C8, C12 and RMSh were not recovered to preoperative levels after 3mo. But the increase of patients after FS- LASIK was smaller than the other two groups, with statistical significance (P<0. 05). CONCLUSION: Compared with SBK and LASEK, FS - LASIK has better visual acuity in the early postoperative and corneal higher-order aberrations increase is relatively small.

Objective To investigate the clinical features of neurobrucellosis and improve the diagnosis and treatment of the disease.Methods The epidemiological information,clinical manifestation,laboratory examination,and imaging characteristics of 30 cases with neurobrucellosis were summarized retrospectively.Results There were 23 men,seven women in this group of cases.The mean age was 43 years.There were six cases with definite history of brucellosis,24 with exposure history of cattle and sheep or their diary products.Brucella blood serum agglutination tests were all positive in 30 cases.Meningitis or meningoencephalitis (29 cases),spinal cord lesion (20 cases) and auditory nerve's damage (18 cases) were the most common forms of neurobrucellosis in these patients.In the cerebral spinal fluid inspection tests,there were 29 cases with increasing leukocyte ((10-599) × 106/L),30 cases with elevated protein (0.5-4.0 g/L),29 cases with decreased glucose (0.8-2.6 mmol/L) in this group of patients.There were 17 cases with white matter lesion on cranial magnetic imaging.The combinations of doxycycline,rifampin and ceftriaxone sodium were given to most cases.The prognosis was good in most cases.Conclusions Neurobrucellosis is not unusual clinically,clinical presentation of which varies greatly.The most common form is meningitis or meningoencephalitis,whereas spinal cord damage and hearing damage are also common.Patients who come from epidemic area and develop unexplained neurological symptoms should be screened and distinguished with neurobrucellosis.

In this study, 101 strains of bacteria were isolated from arct ic water and sediment samples. The methanol extracts of the fermented broth prod uced by these strains were screened in vitro for anti-tumor activity on mou se tsFT210 cells using the method of flow cytometry, and screened for antibacter ial activity by the method of paper disk diffusion. The result showed that one strain exhibited anti-tumor activity and eight strains had antibacterial activ ity. The stability of the antibacterial components produced by strain AR084 an d its optimum medium were also studied. The research indicated that arctic bac teria had potential application in pharmaceutics.

Objective To develop a candidate reference method for the measurement of progesterone in human serum.Methods The serum sample is mixed with the internal standard [3,4-~(13)C_2] progesterone.After extraction with n-hexane and purified by a aqueous solution of 2-Hydroxypropyl-?- cyclodextrin (HP-?-CD),the serum progesterone and labeled progesterone are converted to the 3-enol heptafluorobutyrate and analyzed by gas chromatography mass spectrometry (GC/MS) with selected ion monitoring.The concentration of serum progesterone is calculated by bracketing method.Results The results gave coefficients of variation (CVs) of 0.69% to 2.12%.The analytical recoveries ranged from 98.3% to 100.1%.The results of measuring certified reference materials of serum progesterone are agree with the target value.Conclusion The procedure for measuring progesterone in serum is a highly accurate and precise method and may be used as a candidate reference method for serum progesterone assays.

Studies concerning the association between arsenic exposure and hepatitis B virus (HBV) infection have been lacking.The present study aimed to examine the association between total urinary arsenic (TUA) and infection of HBV.A total of 5186 participants from National Health and Nutrition Examination Survey (NHANES) 2003-2014 were included in the analysis.We used logistic regression to evaluate the association.We defined two measures of TUA.TUA1 was the sum of arsenous acid,arsenicacid,monomethylarsonic acid and dimethylarsenic acid.TUA2 was defined as TUA minus arsenobetaine and arsenocholine.The results showed that the weighted overall prevalence of HBV infection was 6.08％.For NHANES 2003-2014,the medians (interquartile range) of TUA1 and TUA2 were 5.60 μg/L (3.97-8.09 μg/L) and 4.91 μg/L (2.36-9.11 μg/L),respectively.Comparing the highest quartile to the lowest quartile after multivariable adjustment showed that the odds ratios (ORs) and 95％ confidence intervals (CIs) for TUA1 and TUA2 were 2.44 (1.40-4.27) and 2.84 (1.60-5.05),respectively.In conclusion,elevated urinary arsenic was associated with the risk of HBV infection.Further studies,especially prospective studies,are needed to confirm the causal relationship between arsenic exposure and HBV infection.

Objective To compare the biomechanical stability of distal femoral fracture with metaphyseal comminution fixed by unilateral or bilateral locking plates. Methods Distal femoral fracture with metaphyseal comminution (AO type C2.3 fracture) models were established in 22 artificial femoral specimens, and randomly divided into single plate group (group A, n=11) and double-plate group (group B, n=11). In group A, the fractures were fixed by lateral anatomic locking plates, and in group B, the fractures were fixed by lateral anatomical locking plates at lateral side and straight locking plates medially, respectively. In each group, 5 specimens were applied with axial compression and 3 specimens were applied with cyclic axial loading to measure medial subsidence, and the remaining 3 specimens were applied with failure loading to record the maximum load to failure. Results For axial compression, the mean medial subsidence of group A and group B were (2.61±0.28) mm and (0.46±0.08) mm, respectively. For cyclic axial loading, the mean medial subsidence of group A and group B were (1.56±0.12) mm and (0.43±0.05) mm, respectively. For failure loading, the maximum loads to failure of group A and group B were (5 567±338) N and (9 147±186) N, respectively, which all showed significant differences in two groups (P＜0.05). Conclusions For fixing distal femoral fracture with metaphyseal comminution, bilateral locking plates show stronger resistance to medial compression than unilateral locking plates and thus increase the stability of medial column of distal femur, which contributes to patient rehabilitation at early stage.