Objective To evaluate the effects of different doses of dexmedetomidine on atrioventricular node (AVN) conduction function in the healthy volunteers.Methods Sixteen healthy volunteers of both sexes,aged 18-30 yr,with body mass index of 19-26 kg/m2,were included in the study.Dexmedetomidine was infused in a loading dose of 1.0 μg/kg over 10 min,followed by an infusion of 0.5 μg · kg-1 · h 1 for 50 min (Dose Ⅰ);1-2 weeks later,dexmedetomidine was infused in a loading dose of 1.5 μg/kg over 10 min,followed by an infusion of 0.75 μg · kg-1 · h-1 for 50 min (Dose Ⅱ).Before infusion of dexmedetomidine (T0) and at 15 and 35 min of infusion (T1.2),AVN Wenckebach point,AVN 2 ∶ 1 block point,AVN relative refractory period (AVNRRP),and AVN effective refractory period (AVNERP) were measured.Results AVN Wenckebach point and AVN 2 ∶ 1 block point were significantly decreased,and AVNRRP and AVNERP were significantly prolonged at T1,2 compared with those at T0 (P＜0.05).Compared with Dose Ⅰ,AVN Wenckebach point at T2 and AVN 2 ∶ 1 block point at T1,2 were significantly decreased,and AVNRRP and AVNERP were significantly prolonged at T1,2 in the subjects receiving Dose Ⅱ] (P＜0.05).Conclusion Dexmedetomidine can inhibit AVN conduction function in the healthy volunteers,and the inhibitory effect is enhanced with the increasing doses.

Objective To evaluate the effect of dexmedetomidine on heart rate (HR) of rabbits through in vitro and in vivo experiments, and investigate the mechanism by which dexmedetomidine lowered HR.Methods In vitro experiment Healthy adult rabbits of both sexes, weighing 2.0-2.5 kg, aged 8-10 weeks, were studied.The 24 isolated hearts passively perfused in a Langendorff apparatus were randomly divided into 3 groups (n =8 each) using a random number table: control group (group C) , and dexmedetomidine 3 and 30 ng/ml groups (D1 and D2 groups).The isolated hearts were continuously perfused with K-H solution for 45 min in group C.After 15 min of equilibration, the isolated hearts were perfused for 30 min with K-H solution containing dexmedetomidine 3 and 30 ng/ml in D1 and D2 groups, respectively.At 15 min of equilibration, and at 15 and 30 min of perfusion with K-H solution containing dexmedetomidine, HR and left ventricular systolic pressure (LVSP) were recorded.In vivo experiment Twenty-five healthy adult rabbits of both sexes, weighing 2.0-2.5 kg, aged 8-10 weeks, were randomly divided into 5 groups (n=5 each) using a random number table: dexmedetomidine 3, 6, 9, 12, and 15 μg/kg groups (D3, D6, D9, D12, D15groups), to receive the corresponding doses of dexmedetomidine which was intravenously infused over 10 min.HR and mean arterial pressure were monitored and recorded before administration (T0) , and at 15 and 40 min after administration (T1,2).The correlation between doses of dexmedetomidine and change rate of HR was tested by Spearman correlation analysis.Results In vitro experiment Compared with group C, no significant changes were found in HR and LVSP at each time point in D1 and D2 groups (P＞0.05).In vivo experiment Compared with those at T0 , HR at T1 in D6 and D9 groups, HR at T1,2 in D12 and D15 groups, and mean arterial pressure at T1,2in D6, D9, and D12 groups were significantly decreased (P＜0.05) , and no significant change was found in HR at each time point in group D3 (P＞0.05).The correlation coefficient between doses of dexmedetomidine and change rate of HR was 0.944 (P＜0.05).Conclusion The mechanism by which dexmedetomidine lowers HR of rabbits is not related to direct inhibition of sinoatrial nodes, but associated with the balance of autonomic nervous system.

ObjectiveToinvestigatethecorrelationofobstructivesleepapnea(OSAS)andsilentbrain infarction (SBI) in elderly population. Methods A total of 1658 old subjects aged 60 in Beijing and Qingdao w ere screened. Polysomnography (PSG) w as used to conduct the diagnosis and grade of OSAS. MRI w as used to diagnose SBI. Results In al elderly subjects, the prevalences of OSAS and SBI w ere 32.1% and 22.4%. There w ere significant differences in the constituent ratio of the patients w ith hypertension and diabetes, as w el as apnea-hypopnea index (AHI), oxygen desaturation index (ODI), mean oxygen saturation and the low est oxygen saturation betw een the patients w ith OSAS of different severity and the control group. With the increased severity of OSAS, the incidence of SBI increased significantly. The incidences of patients w ith non-OSAS and mild, moderate and severe patients w ith OSAS w ere 13.2%, 30.5%, 43.5%, and 68.8%, respectively. There w as a significant difference betw een the 2 groups ( χ2 =13.365, P=0.004). Multivariable logistic regression analysis showed that hypertension (odds ratio [OR] 2.254, 95%confidence interval [CI] 1.325 to 8.347;P=0.002), diabetes melitus (OR 1.893, 95%CI1.471-8.432;P=0.003) and AHI ≥15 times/h (OR 3.106, 95%CI 1.583-12.571; P<0.001) were the independent risk factors for SBI in elderly population. Conclusions The incidence of OSAS w as higher in the elderly population aged over 60. The incidence of SBI in patients w ith OSAS w as significantly higher than that in patients w ith non-OSAS, and w ith the aggravation of OSAS, it show ed an increasing trend. Moderate to severe OSAS w as an independent risk factor for SBI in elderly population.

The compatibility of traditional Chinese medicines (TCMs) formulae containing enormous information, is a complex component system. Applications of mathematical statistics methods on the compatibility researches of traditional Chinese medicines formulae have great significance for promoting the modernization of traditional Chinese medicines and improving clinical efficacies and optimizations of formulae. As a tool for quantitative analysis, data inference and exploring inherent rules of substances, the mathematical statistics method can be used to reveal the working mechanisms of the compatibility of traditional Chinese medicines formulae in qualitatively and quantitatively. By reviewing studies based on the applications of mathematical statistics methods, this paper were summarized from perspective of dosages optimization, efficacies and changes of chemical components as well as the rules of incompatibility and contraindication of formulae, will provide the references for further studying and revealing the working mechanisms and the connotations of traditional Chinese medicines.
Chemistry, Pharmaceutical ; statistics & numerical data ; Data Interpretation, Statistical ; Drug Incompatibility ; Drugs, Chinese Herbal ; analysis ; Medicine, Chinese Traditional

A chiral LC-MS/MS method for the simultaneous analysis of desvenlafaxine (DVS) enantiomers in human plasma was developed and applied to a pharmacokinetic study on 12 Chinese healthy volunteers. d6-Desvenlafaxine was used as internal standard (IS). Chromatographic separation was performed on the Astec Chirobiotic V chiral column (150 mm x 4.6 mm, 5 μm). The assay was linear over the concentration range of 0.500-150 ng x mL(-1) for both enantiomers (r2 > 0.99). The method was successfully applied to a stereoselective pharmacokinetic study of 100 mg desvenlafaxine sustained release tablets on 12 Chinese healthy volunteers under fasting conditions. The results showed that the pharmacokinetic parameters were similar to both enantiomers in Chinese healthy volunteers. The AUC(0-t), and C(max) of the two enantiomers were about 1.5 times higher than those of blacks and whites reported in the literature.
Administration, Oral ; Area Under Curve ; Asian Continental Ancestry Group ; Chromatography, Liquid ; Cyclohexanols ; blood ; pharmacokinetics ; Delayed-Action Preparations ; Desvenlafaxine Succinate ; Dose-Response Relationship, Drug ; Healthy Volunteers ; Humans ; Male ; Plasma ; chemistry ; Stereoisomerism ; Tablets ; Tandem Mass Spectrometry

Objective To study the accuracy and the clinical significance of sentinel lymph node biopsy (SLNB)after neoadjuvant chemotherapy for breast cancer.Methods A total of 90 patients with StageⅡorⅢbreast cancer and negative axillary node after neoadjuvant chemotherapy were enrolled in the study.Mapping proce- dure and SLNB were performed using methylene blue injected at the site of the primary breast cancer,followed by the axillary lymph node dissection.Results The sentinel lymph node(SLN)was successfully identified in 82 out of 90 patients(91.1%).The number of sentinel harvested nodes ranged from 1 to 4(average 1.6).The accuracy of SLNB to predict the axillary lymph node status was 93.9 %(77/82),the sensitivity,positive predictive value,nega- tive predictive value and false negative rate were 87.5 %(40/45),100 %,88.1% and 11.1%(5/45),respectively. The SLN identification rate tended to be higher and false negative rate tended to be lower in patients with T2 prima- ry tumor before neoadjuvant chemotherapy.Conclusion Our study indicated that SLNB after neoadjuvant chemotherapy in patients with StageⅡorⅢbreast cancer had a similar effect as SLNB in non-neoadjuvant studies. SLNB was considered to be able to accurately predict the axillary lymph node status in patients with T2 primary tu- mor before neoadjuvant chemotherapy.

?AIM:To investigate and analyze diabetic retinopathy ( DR) in patients with type 2 diabetes in local community and risk factors of type 2 diabetic retinopathy, and to provide reference for the prevention and treatment of diabetic.?METHODS:Randomly 268 cases with type 2 diabetes from community health management files from January to March 2015 were selected. Fundus photography was read through the remote reading system, demographic data and laboratory indexes of DR were analyzed.?RESULTS:In the 268 cases with type 2 diabetes, 85 cases were diagnosed as DR ( 31. 7%); there were statistical difference on gender, duration, systolic blood pressure, fasting glucose, glycosylated hemoglobin A1c, urine creatinine between patients with DR and without ( P<0. 05 ). Multivariable Logistic regression analysis showed, duration, systolic blood pressure, fasting glucose, glycosylated hemoglobin A1c were independent risk factors of DR(P<0. 05).?CONCLUSION:Long duration, high blood pressure, high blood glucose are main risk factors of DR, we should strengthen the monitoring of blood pressure, blood glucose and prevent the happening of the DR.

Objective To investigate the changes of cardiac sinus node connexin 45 (Cx45), connexin 31.9(Cx31.9) of gap junction in rabbits'' sinus bradycardia model caused by dexmedetomidine, and to discuss whether the negative frequency and negative conduction caused by Dexmedetomidine are related to the expression changes of connexin.Methods Forty-eight healthy adult New Zealand rabbits were divided into three groups (n=16).Sinus bradycardia rabbits were prepared by intravenous injecting Dexmedetomidine through ear vein.After rabbits were anesthetized by sodium pentobarbital, basic procedures were quickly completed in order to monitor MAP and ECG.Rabbits in group C were injected with normal saline.Rabbits in group D1 were injected a loading dose of dexmedetomidine 10 μg/kg for 10 min, and then continuously pumped 5 μg·kg-1·h-1 for 50 min.Rabbits in group D2 were pumped a loading dose of dexmedetomidine 60 μg/kg for 10 min, and then continuously pumped 30 μg·kg-1·h-1 for 50 min.After observation hearts were quickly removed and sinus node tissue was dissected.The average optical density of sinus node Cx45, Cx31.9 were detected by immunohistochemistry, and the genes expression were detected by real-time quantitative.Results Cx45 gene expression of group D2 showed remarkable increase than groups C and D1(P<0.05), there were no significant differences between groups D1 and C, Cx45 average optical density change were consistent with the gene expression.Cx31.9 gene expression of group D1 showed a more remarkable increase than group C(P<0.05), there were no significant differences between groups D2 and C,D1 and D2, Cx31.9 average optical density changes were consistent with the gene expression.Conclusion Dexmedetomidine increases the expression of low electrical conductivity Cx45, Cx31.9 of gap junction on rabbits'' sinus node, which is one of the possibly reasons that slow down cardiac conduction velocity in sinus node.

To observe the efficacy of herbs for calming liver and suppressing liver-yang in treatment of migraine patients with hyperactivity of liver-yang syndrome and to investigate its effects on the lymphocyte protein expression. This approach may lay a foundation for the further investigation of pathogenic mechanisms in migraine with hyperactive liver-yang syndrome and the curative mechanisms of calming liver and suppressing liver-yang treatment.

Objective To explore the molecular mechanism of the formulae for calming the liver and suppressing YANG in migraine rat model with syndrome of hyperactivity of the liver-YANG.Methods A rat model of migraine with hyperactivity of liver-YANG was established through electrical trigeminal ganglion stimulation and syndrome of oral administration of Fuzi decoction. The total proteins of the lymphocyte in the rats were separated by immobilized pH gradient-based 2-dimensional gel electrophoresis(2-DE), and the 2-DE image was analyzed by PDQuest 7.0 software. Matrix-assisted laser desorption/ionzation-time of flight mass spectrometry (MALDI-TOF-MS) and the SWISS-PORT and MSDB database were used to identify differential proteins.Results The formulae for calming the liver and suppressing YANG could also improve headache. Well-resolution and reproducible 2-DE patterns of rat lymphocyte from normal, model, and therapy tissues were obtained. Eleven of the total 13 differential protein spots were successfully identified by MALDI-TOF-MS. These proteins were alcohol dehydrogenase 3(ADH3), glycogen phosphorylase, ATP synthase D chain, annexin-3, ubiquitin, neutrophil defensin 4 precursor, melanoma-associated antigen E2, heat shock protein-27, annexin-A1, peroxirdoxin-Ⅱ, MU class glutathione S-transferase (Fragment)(GSH). Conclusion Differences occur in the expression of lymphocyte proteins in migraine rats with syndrome of hyperactivity of liver-YANG after treatment with the formulae for calming the liver and suppressing YANG, and the 11 identified protein spots may be associated with its mechanism.