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

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

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

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

Dystonia is a common movement disorder characterized by abnormal gestures and involuntary movement as a result of incoordinate contraction of agonistic and antagonistic muscles.The underlying pathogenesis is very complicated and there are various clinical manifestations.The recent findings in genetics and clinical features of primary dystonia,dystonia-plus syndrome and heredodegenerative dystonia are introduced in this paper.

Objective To investigate the depressing effect of antigene peptide nucleic acid (AGPNA)on the k-ras gene expression of human pancreatic cancer Patu8988 cells, the inducing apoptosis effect on Patu8988 cells, and the biodistribution characteristics in nude mice bearing xenografts using 188Re-k-ras-AGPNA.Methods The expression level of k-ras mRNA and the expression ratio of k-ras protein in Patu8988 cells transfected with AGPNA was measured by RT-PCR and flow cytometry ,respectively. The degree of cellular apoptosis 3 to 5 d after treating Patu8988 cells with 188Re-k-ras-AGPNA or 188ReO4- was determined by flow cytometry. For biodistribution study, 58 nude mice bearing Patu8988 cell xenografts were divided into two groups: intratumoral injection of 188Re-k-ras-AGPNA (Group A) and 188ReO4- (Group B). At different time points, the mice were sacrificed and organs of interest were excised, weighted and counted by a gamma counter. The organ uptake was calculated as a % ID/g and the absorbed doses of organs were calculated. One-way analysis of variance was used. Results After transfected with 1 nmol/ml AGPNA, the k-ras mRNA gray scale ratio and the expression ratio of k-ras protein were 1.00 ± 0.39 and (15.05 ± 5.07)%, respectively. They were significantly lower than those of the control group with 1.86 ± 0.07 and (24. 38 ± 5.40) % (F = 2. 545, 5. 327, P<0. 05). At 4 and 5 d after treatment in Group A, float cells' apoptosis ratios were (26.30 ± 7.45) % and (27.90 ± 10. 38) %, respectively. Tumors were the major distribution site in Group A with uptake of (37.47 ±21.31), (35.96 ±7.80) and (15.46 ±4.93) %lD/g at 1 h, 1 d and 7 d after intra-tumor injection, respectively. The absorbed dose of tumor was 15 569 mGy/MBq. Condusions Transfection with k-ras-AGPNA on Patu8988 cells may inhibit k-ras expression at mRNA and protein expression level, and 188Re-k-ras-AGPNA can induce apoptosis of Patu8988 cells.Tumor is the major distribution site in nude mice bearing human pancreatic cancer xenografts after intratumoral injection of 188Re-k-ras-AGPNA.

OBJECTIVE: To understand the assessment on the criminal responsibility of drug-induced mental disorders and judicial experts' opinions. METHODS: The judicial experts from institutes of forensic psychiatry in Shanghai were selected. They were asked to finish a self-made questionnaire of assessment on the criminal responsibility of drug-induced mental disorders by letters and visits. RESULTS: Most of experts knew the special regulation, "not suitable for evaluation" towards the criminal responsibility of drug-induced mental disorders of the guideline promulgated by Ministry of Justice. Before and after the guideline was issued, no expert made a no-responsibility opinion in such cases. After the guideline was issued, some experts made a full-responsibility or limited-responsibility opinion in such cases. There was a little disagreement among the experts in the case that the crime was unrelated with mental symptoms or the criminals used drugs even though he knew it could induced insanity. But there were still many obvious disagreements among experts in the case that crime was related to such symptoms and person was no ability to debate. Most experts agreed to settle the disagreements with improved legislative perfection. CONCLUSION Most experts are not strictly complying with the assessment guidelines during their practice, and there is still an obvious disagreement towards the criminal responsibility of drug-induced mental disorders.
China ; Crime/psychology* ; Criminals/psychology* ; Data Collection ; Expert Testimony ; Forensic Psychiatry ; Humans ; Liability, Legal ; Male ; Mental Competency ; Mental Disorders/psychology* ; Psychotic Disorders ; Surveys and Questionnaires

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.