As a tumor suppressor, p53 is activated by numerous cellular and environmental signals, and plays a criticalrole in the cell cycle regulation, cell apoptosis and senenscence. The murine double minute (MDM)2 and double minute mu?rine 4 (MDMX) are two important regulators. MDMX is a p53 binding protein with strong sequence homology to MDM2, but lacks ubiquitin ligase activity, and which is unable to target p53 for proteasomal degradation. MDMX regulates p53 activity through its binding with p53 and its postranscriptional modification. MDMX in the closed and open structure binds to p53 to regulate its activity. As the main partner of MDMX, casein kinase 1 alpha (CK1α) disrupts the intramolecular binding in MD?MX in the cooperation to regulate p53 activity. The process of MDMX and CK1αin the regulation of p53 is multi-step and complicated. In this paper the mechanism of MDMX and CK1αin the regulation of p53 protein was reviewed.

Acupuncture Therapy ; Adult ; Female ; Humans ; Laryngitis ; therapy

Acupuncture Therapy ; Aged ; Feeding and Eating Disorders ; therapy ; Humans ; Male

Allostasis ; physiology ; Chronic Disease ; General Adaptation Syndrome ; physiopathology ; Humans ; Stress, Psychological ; physiopathology

OBJECTIVETo investigate the effect of midazolam on human ether-a-go-go (hERG) K+ channels exogenously expressed in human embryonic kidney cells (HEK-293) and the underlying molecular mechanisms.

METHODSWhole-cell patch clamp technique was used to record WT, Y652A and F656C hERG K+ current expressed in HEK-293 cells.

RESULTSMidazolam inhibited hERG K+ current in a concentration-dependent manner, the half-maximum block concentrations (IC50) values were (1.31 ± 0.32) µmol/L. The half-activation voltage (V1/2) were (2.32 ± 0.38) mV for the control and (-1.96 ± 0.83) mV for 1.0 µmol/L midazolam. The half-inactivation voltage (V1/2) was slightly shifted towards negative voltages from (-49.25 ± 0.69) mV in control to (-57.53 ± 0.53) mV after 1.0 µmol/L midazolam (P < 0.05). Mutations in drug-binding sites (Y652A or F656C) of the hERG channel significantly attenuated the hERG current blockade by midazolam.

CONCLUSIONMidazolam can block hERG K+ channel and cause the speed of inactivation faster. Mutations in the drug-binding sites (Y652 or F656) of the hERG channel were found to attenuate hERG current blockage by midazolam.

Dose-Response Relationship, Drug ; Ether-A-Go-Go Potassium Channels ; drug effects ; HEK293 Cells ; Humans ; Midazolam ; pharmacology ; Mutation ; Patch-Clamp Techniques ; Potassium Channel Blockers ; pharmacology

Acupuncture Points ; Acupuncture Therapy ; Adult ; Facial Pain ; therapy ; Female ; Headache ; therapy ; Humans ; Male ; Middle Aged ; Toes

Objective To investigate the effect of valsartan,an angiotensinⅡtype 1 receptor (AT1 R)blocker,on radiosensitivity,invasive potential and proliferation activity of nasopharyngeal carcinoma cells(CNE-2)in vitro. Methods Radiosensitization of valsartan on CNE-2 cells in vitro was investigated by colony forming assay.Effect of ATl R blocker combined with radiation on invasive potential of CNE-2 cells was evaluated using 24-well Matrigel invasion chambers(Transwell).Apoptosis-inducing effect of valsartan combined with radiation on apoptosis of CNE-2 was identified by flowcytometry(FCM). Resuits When valsartan was given at 10-9.10-8 and 10-7 mol/L combined with radiation,sensitivity enhancement ratios (SER)were 1.10,1.20 and 1.36.and the invasive inhibition rates were 8.11%,16.49%and 16.77%,respectively.The SER of valsartan on CNE-2 distinctly increased when the exposure time was increased.After 24 h exposure to 10-8 mol/L valsartan combined witIl radiation.the apoptosis rate was 1.89%±0.09%,which was higher than 1.62%±0.06%in radiation alone group(t=4.79.P＜0.05). Conclusions AT1 R blocker valsartan combined with radiation can significantly inhibit the proliferation activity of nasophar,cngeal carcinoma cells in vitro in a dose- and time-dependent manner.Valsartan combined with radiation can potently inhibit the invasive potential of CNE-2.which may be involved in the mechanism of valsartan treatment in vivo.

ObjectiveTo explore the correlation between open field test(OFT) and light-dark box (LDB),as two animal models of state anxiety in Kunming mice.MethodsThe behavior of adult,male,Kunming mice in OFT and LDB was recorded by sequence,for five minutes,with a one-week inter-trial interval.The following parameters were evaluated:percentage of time exploring in the OFT central area( OFT-Ctime％ ) ; percentage of squares crossing in the OFT central area( OFT-Ccross％ ) ; total number of squares crossing in OFT(OFT-Cross) ;total number of rears in the OFT(OFT-Rear) ; number of fecal boli in OFT(OFT-FB) ; percentage of time exploring in the LDB light area( LDB-Ltime％ ) ; percentage of squares crossing in the LDB light area( LDB-Lcross％ ) ;and percentage of rears in the LDB light area( LDB-Lrear％ ) ; transitions between two areas in LDB( LDB-Transition) ; total number of squares crossing in LDB(LDB-Croas) ; total number of rears in LDB(LDB-Rear) ; number of fecal boli in LDB (LDB-FB).Subsequently,factor analysis,cluster analysis and correlation analysis were calculated for these parameters.ResultsFactor analysis and cluster analysis of variances from either OFT or LDB revealed a three behavioral dimensions:anxiety factor ( loaded by OFT-Ctime％,OFT-Ccross％ or LDB-Ltime％,LDB-Lcross％,LDB-Lrear％ ),activity factor ( loaded by OFT-Cross,OFT-Rear or LDB-Transition,LDB-Cross,LDB-Rear) and emotionality factor(loaded by OFT-FB or LDB-FB).While all the variances from both OFT and LDB in combination were analyzed,it could be seen as five components:' LDB-anxiety factor ( loaded by LDBLtime％,LDB-Lcross％ and LDB-Lrear％ ),' OFT-anxiety factor ( loaded by OFT-Ctime％ and OFT-Ccross％ ),'LDB-activity factor (loaded by LDB-Transition,LDB-Cross and LDB-Rear),'OFT-LDB-emotionality factor( loaded by OFT-FB and LDB-FB) and 'OFT-activity factor (loaded by OFT-Cross and OFT-Rear).Good correlation were found between OFT/LDB factors alone and in combination,such as OFT-emotionality factor and LDB-emotionality factor(Pearson =0.383,P＜0.05),LDB-anxiety factor and 'LDB-anxiety factor( Pearson =0.989,P＜0.01 ),OFT-anxiety factor and 'OFT-anxiety factor( Pearson =0.934,P ＜ 0.01 ),LDB-activity factor and 'LDB-activity factor ( Pearson =0.956,P ＜ 0.01 ),OFT/LDB-emotionality factor and ' OFT-LDB-emotionality factor ( Pearson =0.835,P＜0.01 ;Pearson =0.696,P＜0.01 ),OFT-activity factor and 'OFF-activity factor( Pearson =0.926,P＜0.01 ).ConclusionEither OFT or LDB comprised three behavioral dimensions:anxiety factor,activity factor and emotionality factor; however,it was difficult to establish face validity as a point-to-point concordance between OFT and LDB.Attention should be paid to heterogeneity of animal models when OFT and LDB were in combination as a behavionomics to evaluate anxiolytics in Kunming mice.

BACKGROUND:Deep venous thrombosis is one of the most common and dangerous complication. There wil be serious consequences for failing to prevent deep venous thrombosis in advance, so we need to evaluate the risk factors of deep venous thrombosis. OBJECTIVE:To evaluate the clinical risk factors for lower limb deep vein thrombosis after total hip arthroplasty. METHODS:Data of 162 patients who were treated from January 2010 to February 2013 in Department of Bone and Joint Surgery, Shenzhen Hospital of Peking University for total hip arthroplasty were analyzed retrospectively. Al patients received ultrasonography on deep veins of lower limb preoperatively and postoperatively 3 and 7 days. Risk factors of deep venous thrombosis were analyzed using Logistic regression analysis in patients undergoing total hip arthroplasty. RESULTS AND CONCLUSION:The selected factors for Logistic regression model contained bone cement prosthesis, age distribution, body mass index, and general anesthesia. Their OR values were 9.215, 11.247, 3.842, 4.825, respectively. They were risk factors for the occurrence of deep venous thrombosis. Above results indicated that use of bone cement prosthesis, age, body mass index>25 kg/m2 and general anesthesia are risk factors for deep venous thrombosis after total hip replacement, so they should cause clinical attention and we should take active measures to prevent them.

Editor's Notes: The basic theory of traditional Chinese medicine is the theoretical foundation of Chinese medicine , modernization of Chinese medicine needs of the modern theory of Chinese medicine urgently . However , it is always the important issues about how modern Chinese medicine theory should be created , and what kind of theory should have been established concerned and explored by domestic and foreign counterparts in tradi-tional Chinese medicine . To lead the development of modern Chinese medicine theory , Modern Basic Theory of Traditional Chinese Medicine series of symposiums are set up specially in the current Review column, and discussed thoroughly and systematically using three consecutive pats respectively. Among them, part I contains 3 articles about new concepts, new theories, new disciplines; part II contains 5 articles about new ideas, new norms, how to clear concept, how to verify hypotheses, why to evaluate theory; part III contains 12 articles about concept of wholism updating, treatment based on syndrome differentiation development, viscera-state doc-trine innovation, pathogeny, etiology, pathogenesis, prevention, principle of treatment, knowledge structure, cogni-tion structure , monographic study , 5-year outlook . Published article on this issue is the first one belong to new concept of part I. In this paper, we want to describe the denotation and connotation of the new concept of the modern basic theory of traditional Chinese medicine from three aspects of a concept: a label , a theoretical definition , and an operational definition learning from the international academic understanding of scientific concepts, demonstrate the necessity of theoretical premise to the research and establishment of the modern basic theory of traditional Chinese medicine and the need to build on , illustrate the inevitable trend toward modern science . The whole article contains profound meaning and a certain breakthrough and innovation. We are expected to cause concerns and discusses of experts and scholars through this article .