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.

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.

Molecularly imprinted polymers for dimethoate recognition were synthesized by the precipitation polymerization technique using methyl methacrylate (MMA) as the functional monomer and ethylene glycol dimethacrylate (EGDMA) as the cross-linker. The morphology, adsorption and recognition properties were investigated by scanning electron microscopy (SEM), static adsorption test, and competitive adsorption test. To obtain the best selectivity and binding performance, the synthesis and adsorption conditions of MIPs were optimized through single factor experiments. Under the optimized conditions, the resultant polymers exhibited uniform size, satisfactory binding capacity and significant selectivity. Furthermore, the imprinted polymers were successfully applied as a specific solid-phase extractants combined with high performance liquid chromatography (HPLC) for determination of dimethoate residues in the cucumber samples. The average recoveries of three spiked samples ranged from 78.5% to 87.9% with the relative standard deviations (RSDs) less than 4.4% and the limit of detection (LOD) obtained for dimethoate as low as 2.3μg/mL.

Objective To analyze the sensitivity of auxiliary examinations in different periods of sporadic Creutzfeldt-Jakob disease (sCJD).Methods The clinical data of 53 sCJD patients were retrospectively analyzed including the different stages of skull diffusion-weighted magnetic resonance imaging (DWI),24-hour ambulatory electroencephalogram (EEG),18F-FDG PET/CT (PET-CT)and cerebrospinal fluid 14-3-3 protein.When calculating the sensitivity of an auxiliary examination,the diagnostic criteria were defined by combining the specific clinical manifestations with two or more positive results of other auxiliary examinations.Results There were 24,53 and 22 sCJD patients,respectively,met the criterion of early (E),middle (M) and later (L) stage of disease (some patients fit 2 or 3 stages).The sensitivity ofDWl (E:58.3％ M:85.4％,L:94.7％),EEG (E:45.8％,M:62.7％,L:77.8％),14-3-3 protein in cerebrospinal fluid (E:11.1％,M:52.9％) and PET-CT (E:80％,M:100％) increased gradually with disease progression,The sensitivity of PET-CT was higher than the other auxiliary examinations for E and M stages;no PET-CT was conducted in L stage.High signal regions mainly distributed in the cortex in E and M stages,but in L stage,no significant difference was found on the distribution of high signal regions between cortex and basal ganglia.Conclusions The sensitivities of the auxiliary examinations were different for sCJD patients in different stages.Reexaminations in different periods may improve the sensitivity for sCJD diagnosis.The sensitivity of PET-CT was high,and the combination of PET-CT and other auxiliary examinations may play a key role in the diagnosis of sCJD.

Objective To test the effects of Vitamin D (VitD) on endothelial nitric oxide(NO) production and to study the signal pathway leading to NO release.Methods In vitro cultured human umbilical vein endothelial cells (HUVEC) were treated with various concentrations of VitD(0 mmol/L,0.01 mmol/L,0.10 mmol/L,1.00 mmol/L,10.00 mmol/L) for 60 min,and VitD at concentration of 1.00 mmol/L at different time points (30 min,60 min,90 min,120 min).The effect of VitD on NO production in presence of VitD receptor(VDR) agonist(ZK191784) or antagonist(ZK159222) for 60 min were examined in cell culture supernatant with kit for the detection of nitric oxide fluorescent probe(DAF-FM DA).HUVEC was cultured with VitD in presence of VDR agonist or antagonist for 60 min,and the effect of VitD on NO production with DAF-FM DA and the protein expression and phosphorylation of Caveolin-1 and endothelial nitric oxide synthase(eNOS) were detected by Western blot,respectively.Results VitD caused a concentration-dependent increase in NO production.The maximum effect was observed at a concentration of 1.0 mmol/L and the optimal time of stimulation was 60 min.Effects induced by VitD were enhanced by VDR agonist,and abolished by antagonist.VitD and VDR agonist maintained the expression of Caveolin-1 at the same low phosphorylation level the same as normal,increased the phosphorylated level of eNOS.However,VDR antagonist increased the phosphorylation of caveolin-l,but reduced the level of eNOS phosphorylation,respectively.Conclusions VitD can induce a significant increase in endothelial NO production through VDR.VitD interaction with VDR causes the low phosphorylation of caveolin-1 leading to eNOS activation and NO production.

Objective To investigate the effect of salt-induced kinase 2 (SIK2) in the G2/M checkpoint in response to ionizing radiation and the possible mechanism.Methods HeLa cells were irradiated with 60Co γ-rays.The cell model of knockdown SIK2 expression was constrcuted by transfecting HeLa cells with a pSicoR-based lentivirus vector of expressing SIK2 shRNA by lipofectamin 2000.Western blot and flow cytometry were performed to measure the changes of SIK2 protein level and cell cycle distribution.The phosphorylated histone protein H3 on Ser 10 was used as a molecular marker of mitotic cells for detecting the function of G2/M checkpoint.Results The expression level of SIK2 protein increased in HeLa cells after 60Co γ-ray irradiation.A cell model of knockdown SIK2 expression was successfully generated by transfecting the specific shRNA against SIK2.Depression of SIK2 significantly increased the cellular sensitivity at 1,2,4,6 Gy post-irradiation (t =-3.445,-2.581,-3.251,-2.553,P ＜0.05),and led cells to release earlier from the G2/M boundary arrest compared to control cells at 5,6 h post-irradiation (t =4.341,6.500,P ＜ 0.05).Western blot analysis indicated that the irradiation-induced phosphorylated CHK2/T68 in SIK2 knock-down cells was earlier than that in control cells.Conclusions salt-induced kinase 2 (SIK2) participates in the regulation of G2/M checkpoint induced by ionizing radiation and affects cellular radiosensitivity.

BACKGROUND:Light-cured composite resin is used for dental crown defective repair in terms of both function and morphology.
OBJECTIVE:To investigate the therapeutic effects of light-cured composite resins on crown defects.
METHODS:Relevant literatures concerning light-cured composite resins for repair of crown defects were retrieved. Literatures which met the study standard were deeply analyzed. Meanwhile, fol ow-up results and literature results were compared for patients receiving light-cured composite resins for repair of crown defects to identify the feasibility of light-cured composite resins for repair of crown defects.
RESULTS AND CONCLUSION:Based on the included data, the successful rate of light-cured composite resins for repair of crown defects was over 90%. Clinical fol ow-up of 12 patients undergoing light-cured composite resin showed that the repaired crowns were stable and fixed, and exhibited a symmetrical appearance with the contralateral namesake tooth of the adjacent tooth, and there was a normal bite relationship. During the fol ow-up study, 19 teeth repaired from 12 patients had no loosing, no shedding, no percussion pain and normal bite relationship. X-ray films showed no apical shadows. Light-cured effects were limited to the upper and middle parts but not to the apical part. Therefore, a better therapeutic effect can be obtained.

Objective To analyze the current situation and influence factors of ordinary medical college undergraduates' contact with scientific research at early stage in order to provide references for scientific research.Methods Totally 1940 students majoring in clinical medicine,imaging,traditional Chinese medicine and nursing (2008 -2010 grade) in China Three Gorges University were enrolled to do questionnaine and SPSS 17.0 was used to do statistical analysis.Results Totally 1653copies of questionnaires were collected from 1940 students,the recovery rate was 85.21％.Two hundred and nineteen students ( 13.25％ ) participated in scientific research,65.28％ students thought college propaganda to be ordinary,95.43％ students got benefits from scientific research.The main influence factors of scientific research were lack of time (23.73％),insufficient knowledge reserves (22.03％) and researchers' own problems (39.73％).Conclusions Medical school should expand the range of scientific research and strengthen propaganda.Medical students should arrange research time and constantly improve their comprehensive ability so as to achieve good results.

Intraoperative radiotherapy (IORT) is a radiotherapy method that uses a radiotherapy device to provide a brachytherapy with single high-dose radiation to a target tissue (primary tumor beds,residual tumors,and lymphatic drainage areas) during surgery,which includes intraoperative electron beam radiotherapy and high-dose-rate intraluminal brachytherapy.Nowadays,the implementation of precise radiation dose is an important part of multidisciplinary,individualized treatment of tumors.IORT achieves precise treatment by maximizing the radiation dose to the target volume and protecting surrounding normal tissues as much as possible.This article describes the recent research on IORT.

Several studies have shown that human epidermal growth factor receptor 2 (HER2) amplification could be a predictive biomarker of resistance to anti-epidermal growth factor receptor monoclonal antibodies in patients with RAS wild-type metastatic colorectal cancer (mCRC). Dual HER2 inhibition with trastuzumab plus lapatinib or pertuzumab has shown promising preliminary anti-tumoral efficacy in RAS wild-type mCRC. HER2-targeted therapeutic strategies have the potential to change the treatment paradigm for a clinically relevant subgroup of patients with mCRC.