OBJECTIVE: To establish a HPLC method for the determination of serum concentration of caffeic acid in rats and which was applied to the pharmacokinetic study of caffeic acid. METHODS: The concentrations of caffeic acid in rats were determined after intragastric (ig) administration or intravenous (iv) administration of 50 mg?kg-1 caffeic acid and the pharmacokinetic parameters of caffeic acid analyzed by Topfit 2.0. RESULTS: The main pharmacokinetic parameters of caffeic acid after ig administration of caffeic acid were as follows: Cmax: (0.56?0.12) ?g?mL-1; tmax: (0.18?0.04) h; t1/2: (0.67?0.12) h; ke: (1.05?0.20) h-1; AUC(0～t): (0.34?0.05) ?g?h?mL-1. The main pharmacokinetic parameters of caffeic acid via iv administration were as follows: t1/2: (0.45?0.05) h; ke: (1.55?0.18) h-1; AUC(0～t): (9.07?2.24) ?g?h?mL-1. CONCLUSION: Administered intragastrically, caffeic acid was characterized by rapid absorption, short elimination half life (t1/2) and low absolute bioavailability in rats.

OBJECTIVE:To determinate the metabolites of ranolazine in rats by LC-MSn.METHODS:Rats were given 80 mg?kg-1 ranolazine by i.g.During 0～24 h after intragastrical administration,the sample of urine was collected and extracted by solid phase column.Extracts were determined by LC-MSn.The mobile phase consisted of acetonitrile,10 mmol?L-1ammonium acetate and glacial acetic acid at a flow rate of 0.5 mL?min-1.Fragmentation ions of ranolazine and its metabolites were determined in positive electrospray ionization by using MS,MS2 and MS3 full scans.RESULTS:Twelve phaseⅠ metabolites (O-demethylation,O-dearylation,hydroxylation,N-dealkylation and amide hydrolysis) and nine phase Ⅱ metabolites(O-glucuronidation and sulfation) were found in the sample.CONCLUSION:Ranolazine is extensively metabolized in rats.

OBJECTIVE:To study the metabolite and excretion of polydatin (Trans-resveratrol-3-O-glucoside,TRG) and its metabolites in Beagle dog feces,and provide experimental basis for the new drug development of TRG. METHODS:4 Beagle dogs were intragastrically administrated TRG 20％ polyethylene glycol 400 solution 50 mg/kg. LC/MS was used to identify the me-tabolites of TRG in dog feces after 12-24 h of administration,and HPLC was adopted to determine the cumulative excretion rate and excretion speed rate of the major metabolite resveratrol(TR)in feces samples after 0-12,12-24,24-36,36-48,48-72,72-96 h of administration. RESULTS:TR and two sulfate conjugates of TR were found in dog feces,and TR was a major metabolite, while TRG was undetermined. The excretion speed rate of TR in dog feces was the rapidest after 12-24 h of administration,reach-ing 9.65 mg/h. Its cumulative excretion rate was 39.3％,equivalent to 67.2％ of TRG. CONCLUSIONS:After TRG is intragastri-cally administrated to dogs,TRG was mainly excreted in the form of TR via dog feces.

Objective T o investigate the expression of hyperpolarization-activated cyclic nucleotide-gated cation channel 4 (H C N 4) and connexin43 (C x43) in the sinoatrial node of electric shock death. Meth-ods As experim ental group, 34 cases of electric shock death who had definite current m ark evidence were selected from pathology departm ent of X uzhou M edical C ollege from 2010 to 2013. As the control group, 20 cases of fatal severe craniocerebral injury in traffic accidents were chosen. T he expressions of H C N 4 and C x43 in the sinoatrial node were observed by im m unohistochem ical technology. Results H C N 4 positive cells expressed in the cell m em brane and cytoplasm of the sinoatrial node. C x43 positive cells expressed in the cell m em brane and cytoplasm of T cells and m yocardial cells. T he expression of H C N 4 was significantly higher than that of the control group (P<0.05) and the expression of C x43 was signifi-cantly lower than that of the control group (P<0.05). Conclusion T he changes of H C N 4 and C x43 ex-pressions in the sinoatrial node illustrate electric shock death m ight be related to the abnorm alities of cardiac electrophysiology and conduction.

Objective: To discuss the characteristics of symptoms improvement based on the follow-up evaluation of Eustachian tube balloon dilation medium to long-term efficacy in patients with symptomatic Eustachian tube dysfunction (SETD). Methods: Patients from 2015 to 2017 were followed up after Eustachian tube balloon dilation (with the sense of aural fullness, or tinnitus and hearing ambiguity). All participants had been done ETDQ-7 before surgery and were re-evaluated with ETDQ-7 in follow-up. The improvement of overall and individual symptoms scores in ETDQ-7, the effects of gender and the difference of scores at different stages (12-18 months, 18-24 months and 24-30 months) after the operation were analyzed. Results: There were 29 patients, including 16 males and 13 females, whose age ranged from 20 to 62 years old. The medium to long-term score of ETDQ-7 significantly declined after surgery (27.0±7.9 vs. 14.1±7.5, P<0.05). Among all symptoms, symptoms like "blockage feeling in ear or being like under the water, constriction feeling" , "sound of blisters or explosions in the ear" decreased obviously (P<0.05). Comparing different stages after surgery, the scores of ETDQ-7 existed no difference (P>0.05). And the difference of gender showed no significant influence on surgery effects. Conclusion The subjective symptoms of patients with Eustachian tube dysfunction diagnosed with SETD can be significantly improved in the medium to long-term follow-up after Eustachian tube balloon dilation, and the degree of improvement is not linearly related to the postoperative time.