OBJECTIVETo preliminarily study the effective dosage range and mechanism of the abirritation of volatile oil of Evodia Fructus on the stomach cold syndrome model in mice, and discuss the correlation between its accompanying toxicity and oxidative damage mechanism, in order to provide the experimental basis for explaining the efficacy-syndrome-toxicity correlation.

METHODThe stomach cold-syndrome model in mice was induced by the classic hot plate test by orally administrating with different doses of volatile oil of Evodia Fructus, in order to observe its abirritation and companying toxic and side effects and detect serum ALT, AST, PGE2, NO, NOS, MDA, SOD, GSH, GSH-Px, BUN, CR and hepatic ALT, AST. The companying toxic symptoms in mice were recorded in toxic reaction integral table.

RESULTVolatile oil of Evodia Fructus had an obvious analgesic effect at 30 min after the oral administration and reached the peak effect at 60 min, with certain "dose-effect" and "time-effect" relations, rises in serum and hepatic ALT and AST levels, serum PGE2, MDA, NO and NOS and hepatic indexes, decreases in SOD, GSH and GSH-Px and no notable change in BUN, CR levels and kidney weight/body ratio. Conclusion: The abirritation mechanism of volatile oil of Evodia Fructus was related to the inhibition of pain transmitter release, peroxidative damage and NO damage, which is accompanied by certain hepatotoxicity, mainly mainly oxidative damage, with a concurrent "dose-time-toxicity" relationship.

Animals ; Drugs, Chinese Herbal ; administration & dosage ; toxicity ; Evodia ; chemistry ; toxicity ; Female ; Fruit ; chemistry ; toxicity ; Humans ; Liver ; drug effects ; metabolism ; Mice ; Oils, Volatile ; administration & dosage ; toxicity ; Oxidative Stress ; drug effects ; Stomach ; drug effects ; metabolism ; Stomach Diseases ; drug therapy ; metabolism

The range of effective dose and mechanism of abirritation about water extraction components of Evodiae Fructus on the stomach cold syndrome model in mice were preliminary studied. The method of stomach cold-syndrome model in mice was built, which were administrated with different doses water extraction components of Evodiae Fructus, observing abirritation and toxicity by the classical hot plate method, detecting the level of ALT, AST, PGE2, NO, NOS, MDA, SOD, GSH, GSH-Px, BUN, CR in serum and ALT, AST in hepatic tissue, and recording toxicity symptoms in mice according to the list of relevant toxicity reaction. The water extraction component of Evodiae Fructus has obvious analgesic action after administration 30 min, arriving peak effect after administration 60 min, showing certain "dose-time-toxicity" relationship. ALT and AST levels in mice serum and liver tissue enhanced; PGE2, MDA, NO, NOS enhanced in mice serum; SOD, GSH, GSH-Px reduced; the BUN, CR levels was no significant alteration; liver weight/ body weight enhanced; kidney weight/body weight was no significant alteration. The a irritation mechanism of volatile oil of Evodiae Fructus was connected with suppressing pain transmitters release, per oxidative damage mechanism and NO damage, which also induced hepatotoxicity and the mechanism of hepatotoxicity is main lyoxidative damage, showing certain "dose-time-toxicity" relationship in accordance to hepato-toxicity injury.
Analgesics ; pharmacology ; Animals ; Body Weight ; drug effects ; Chemical and Drug Induced Liver Injury ; etiology ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Evodia ; toxicity ; Female ; Medicine, Chinese Traditional ; Mice ; Plant Extracts ; pharmacology ; toxicity

Adult ; Humans ; Male ; Neck Injuries ; complications ; Pharynx ; injuries ; Trachea ; injuries

Aneuploidy ; Animals ; Cervical Intraepithelial Neoplasia ; genetics ; pathology ; DNA, Neoplasm ; analysis ; Diagnosis, Differential ; Female ; Image Cytometry ; methods ; Neoplasms, Squamous Cell ; genetics ; pathology ; Prognosis ; Uterine Cervical Neoplasms ; genetics ; pathology

OBJECTIVETo study the anti-immune inflammation efficacy and toxicity of Tripterygium wilfordii decoction, in order to provide experimental basis for studies on its "efficacy-toxicity" correlation.

METHODThe delayed hypersensitivity model was established by dinitrofluorobenzene in mice. Different doses of T. wilfordii decoction was administered for 5 consecutive days. The ear swelling inhibition ratio and the toxic action were observed. After the final administration, the biochemical indexes of PGE2, TNF-α, IL-2, ALT, AST, PA, TBA, TBIL in serum were detected, and the visceral indexes of heart, liver, spleen and kidney were measured.

RESULTThe DNFB-induced ear swelling could be notably inhibited by multiple oral administration of T. wilfordii decoction, with the ED50 and its 95% confidence limit of 0.34 (0.21-0.42) g x kg(-1). The contents of PGE2, TNF-α, IL-2 in serum decreased in a dose-dependent manner. The activities of serum AST, ALT, TBA, TBIL and the PA content reduced.

CONCLUSIONT. wilfordii decoction shows a significant anti-immune inflammation efficacy within the dosage range between 0.59 and 2.34 g x kg(-1) in a dose-dependent manner. With a certain hepatotoxicity, high dose (2.34-4.68 g x kg(-1)) of T. wilfordii decoction can cause substantial liver injury, with a dose dependence in liver function index. Therefore, the efficacy and toxicity of T. wilfordii is dose dependent, which provides reference for preventing adverse drug reactions in clinic and developing early-warning schemes and ensure the clinical medication safety of T. wilfordii.

Animals ; Anti-Inflammatory Agents ; administration & dosage ; chemistry ; toxicity ; Drug Dosage Calculations ; Drug Evaluation, Preclinical ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; toxicity ; Edema ; drug therapy ; genetics ; immunology ; Humans ; Interleukin-2 ; genetics ; immunology ; Male ; Mice ; Tripterygium ; chemistry ; toxicity ; Tumor Necrosis Factor-alpha ; genetics ; immunology

The new generation cyclooxygenase (COX-2) inhibitor could reduce the gastrointestinal side effect of NSAID drugs, but eventually increase the cardiovascular risk, because its selective inhibition of COX-2 induces the imbalance between PGI2 and TXA2 and the reduction of vasodilatory NO. Under pathological conditions, active oxygen species (O2-*2, etc) were used to induce endo- thelial dysfunction, activate NF-κB to induce expressions of pro-inflammatory cytokines IL-1β and TNF-α, increase ET-1, TXA2 with vasoconstrictor effect, reduce PGI2 and NO with vasodilatory effect, generate further oxidative damage together with NO, and reduce the bioavailability of NO. NO-NSAIDs and NO-Coxibs drugs raised the level of NO by introducing NO-donor (ONO2). NSAIDs drugs enhanced the anti-inflammatory activity of COX-2 and reduced gastrointestinal side effects by inhibiting selectively COX-2. If antioxidant structures with active ingredients of traditional Chinese medicines were introduced to improve the antioxidant activity of NSAIDs, they could scavenge the active oxygen species to protect the normal function of vascular endothelia and enhance the bioavailability of NO, which is conducive to enhance the cardiovascular safety of cyclooxygenase (COX-2) inhibitor.
Anti-Inflammatory Agents ; therapeutic use ; Biomarkers, Pharmacological ; Cardiovascular Diseases ; drug therapy ; enzymology ; immunology ; Cyclooxygenase 2 ; immunology ; Cyclooxygenase 2 Inhibitors ; adverse effects ; therapeutic use ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; NF-kappa B ; immunology ; Reactive Oxygen Species ; immunology ; Tumor Necrosis Factor-alpha ; immunology

In Chongqing Medical University,Introduction to Clinical Medicinewas first launched in 2002. In this article, based on the summary of 2014 to 2015, we summarized respectively from teaching material construction, evaluation system with combination of formative assessment and summative assess-ment, network support platform, teaching quality monitoring system, and student questionnaire survey and evaluation. Through the study of the course, 99.5% (836/840) of the students think their team conscious-ness and cooperation ability were improved, 94.2% (791/840) of the students consider this course can im-prove their innovative ability of self-learning, 87.0% (731/840) of the students think it is beneficial to the improvement of their self expression ability and more than 78.0% of the students think they have achieved the goal of early clinical contact, expanding knowledge, and enhancing the basic professional quality.

OBJECTIVE:To study the process of acetylized racemization of D-penicillamine in the acidic condition. METHODS:The acetylized racemic mixture of D-penicillamine was prepared by racemizing acetyl chloride in acetic acid solu_tion with D-penicillamine as feedstock.The preparation process was optimized with the quantities of solvent and acetyl chloride,the reaction temperature,the reaction time etc.as parameters.The influence of reaction temperature,reaction time on the specific optical rotation in the acetylized process was determined and the kinetic equation of acylation process was computed. RESULTS:The optimal condition for racemization was the following,the quantity ratios of D-penicillamine-acetic acid -acetyl chloride were 1∶7∶2,the reaction temperature was 80℃ and the reaction time was 5h.The kinetic equation of acylation process fitted first order linear relation. CONCLUSION:This preparation process is mild and simple,and it offers direct feedstock for the preparation of D,L-penicillamine.

Brucellacapt is a new serological test based on immunocapture-agglutination technique that has been used in many countries ,but there was no related article reported in China .The value of the Brucellacapt method in diagnosing human brucellosis was evaluated in this study .Among 120 suspected patients ,75 patients and 45 negatives were diagnosed by SAT and RBPT method combination with their clinical symptoms .Sera from all 120 people were tested by the method of Brucella-capt and iELISA ,and the results were ,consequently ,analyzed and compared .It showed that sensitivity ,specificity ,consis-tency rate ,Kappa value ,and area under ROC curve were found to be 82 .7% ,88 .9% ,85 .0% ,0 .69 ,and 0 .86 ,respectively for Brucellacapt ,whereas they were found to be 90 .7% ,64 .4% ,80 .8% ,0 .57 ,and 0 .78 for iELISA .In conclusion ,specific-ity ,consistency rate ,Kappa value ,and area under ROC curve were higher in Brucellacapt method than that in iELISA .How-ever ,the sensitivity of iELISA is higher .

OBJECTIVETo study the effect of single administration of aqueous extracts from aconite on "dose-toxicity" relationship and "time-toxicity" relationship of mice hearts, through changes in electrocardiogram (ECG) and serum biochemical indexes.

METHODMice were grouped according to different drug doses and time points, and orally administered with water extracts from aconite for once to observe the changes of mice ECG before and after the administration, calculate visceral indexes heart, liver and kidney, and detect levels of CK, LDH, BNP and CTn-I in serum.

RESULTAccording to the "time-toxicity" relationship study, at 5 min after oral administration with aqueous extracts from aconite in mice, the heart rate of mice began rising, reached peak at 60 min and then slowly reduced; QRS, R amplitude, T duration and amplitude and QT interval declined at 5 min, reduced to the bottom at 60 min and then gradually elevated. The levels of CK, LDH, BNP and CTn-I in serum elevated at 5 min and reached the peak at 60 min, with no significant change in ratios of organs to body at different time points. On the basis of the "dose-toxicity" relationship, with the increase in single dose of aqueous extracts from aconite, the heart rate of mice. QRS, T duration and amplitude and QT interval declined gradually, and levels of CK, LDH, BNP and CTn-I in serum slowly elevated, with a certain dose dependence and no significant change in ratios of organs to body in mice.

CONCLUSIONSingle oral administration of different doses of aqueous extracts from aconite could cause different degrees of heart injury at different time points, with a certain dose dependence. Its peak time of toxicity is at 60 min after the administration of aqueous extracts from aconite.

Aconitum ; adverse effects ; chemistry ; Animals ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; administration & dosage ; isolation & purification ; toxicity ; Female ; Heart ; drug effects ; physiology ; Heart Rate ; drug effects ; Kidney ; drug effects ; Liver ; drug effects ; Male ; Mice