Objective: To establish and validate a LC-MS/MS method for quantitative analysis of a new anti-stroke compound TID-101 in rat plasma and to study the pharmacokinetics and bioavailability of TID-101 self-(micro)emulsified drug delivery system(SMEDDS). Methods: The plasma samples were treated with methanol for precipitating protein. The chromatographic separation was achieved with a acetonitrile-water mobile phase. Detection of TID-101 and the internal standard (IS) dexamethasone acetate was achieved by electrospray ionization (ESI) source in the negative ion mode at m/z 353.4→323.2 and m/z 433.4→353.4. The method was applied for pharmacokinetics study of TID-101 between SMEDDS in rats. Results: The method was linear over TID-101 concentration range from 10-95 000 ng/ml with the correlation coefficients (r) of 0.9998. The intra-run and inter-run relative standard deviations(RSD) were less than 15% and the average absolute recovery values were 83.4-87.0%. The validated method was applied to a pharmacokinetic study in rats after intravenous administration of TID-101 fat emulsion injection and oral administration of TID-101 suspension and SMEDDS. The bioavailability of TID-101 API and SMEDDS was 2.8% and 14.9%, respectively. Conclusion: The analysis method is simple, accurate, and sensitive for assaying the in vivo pharmacokinetic study of TID-101 in rats. SMEDDS could effectively enhance the oral bioavailability of TID-101.

Objective To investigate the factors affecting health-related quality of life (HRQOL) in patients with chronic liver disease (CLD).Methods HRQOL was measured with SF-36v2 Chinese version.All patients with CLD diagnosed between December 2009 and May 2011 in Liver Research Center,Beijing Friendship Hospital and Digestive Department,Beijing Chaoyang Hospital were enrolled in this study.Patients with CLD were divided into 4 groups according to their Child-Turcotte-Pugh scores:no cirrhosis,Child's classes A,B,and C.Demographic and clinical data were collected in each group.Results A total of 392 patients with CLD and 91 healthy controls were included.HRQOL in patients with CLD was lower than that in healthy controls.Physical component score (PCS) in healthy controls was 54.6 ± 5.5,and in CLD was 47.8 ± 8.8 (t =9.343,P ＜ 0.01).Mental component score (MCS) in healthy controls was 56.4 ± 8.1,and in CLD was 51.7 ± 7.4 (t =5.302,P ＜ 0.01).Increasing severity of CLD from no cirrhosis to advanced cirrhosis was associated with a decrease on HRQOL,PCS scores were 53.1 ± 5.9,48.7 ± 6.6,42.4 ± 7.1 and 37.2 ± 8.9 (F =93.353,P ＜ 0.01) ; MCS scores were 53.2 ± 4.8,52.7 ±6.5,51.8 ±7.5,and 46.8 ± 7.5 (F =11.325,P ＜0.01),for no patients with cirrhosis,Child's classes A,B and C respectively.Stepwise linear regression analysis showed that severity of disease,age,present ascites,present varices,and prothrombin time had significant effects on physical health area (F =100.893,P ＜ 0.010).Severity of disease,female gender,present varices,total bilirubin,prothrombin time and hemoglobin had significant effects on mental health area (F =19.237,P ＜ 0.010).Conclusions Patients with CLD have reduced HRQOL.Increasing severity of CLD is associated with a decreasing HRQOL.Old age,female gender,advanced stage of CLD,present ascites,hyperbilirubinemia and prolonging prothrombin time are risk factors for reducing HRQOL.

Colon, Sigmoid/surgery* ; Colostomy ; Humans ; Ostomy ; Prolapse ; Surgical Stomas

Animals ; Brain-Derived Neurotrophic Factor ; metabolism ; Hypothalamus ; metabolism ; Male ; Physical Conditioning, Animal ; physiology ; Rats ; Rats, Sprague-Dawley

Aged ; Humans ; Male ; Middle Aged ; Penis ; innervation ; Prostatectomy ; methods ; Prostatic Neoplasms ; surgery

OBJECTIVETo summarize our experiences in anesthetic management for the resection of tracheal masses.

METHODSThe clinical data of 15 patients with tracheal masses in Peking Union Medical College Hospital from 2002 to 2012 were analyzed retrospectively. Remarkable dyspnea and tracheal stenosis were observed in 12 patients. Standard orotracheal intubation was carried out in patients with less than 50% of tracheal lumen obstructed. The location of masses was critical for those with severe tracheal stenosis. Local anesthetics were applied and tracheostomy were performed in patients with masses located at the upper part of the trachea. Intubation above the masses was established in patients with masses located at the lower part of the trachea. Percutaneous cardiopulmonary support was introduced before anesthetic induction in a patient with severe respiratory distress and hypercapnea,then an endotracheal tube successfully passed the stenosis guided by a fiberoptic bronchoscope. General anesthesia was induced intravenously and muscle relaxants were applied in all patients. Succinylcholine was administrated in 5 of 6 difficult patients.

RESULTSAirway management and anesthesia were performed successfully in all the 15 patients. After the operations,patients were extubated and discharged from the hospital without difficulty in respiration.

CONCLUSIONSThe successful airway management of tracheal masses depends on the degree and location of stenosis and the severity of dyspnea. Extracorporeal circulation is an optimal choice for those with critical airway occlusion and adequate oxygenation can not be accomplished with conventional anesthesia.

Adolescent ; Adult ; Aged ; Airway Management ; methods ; Anesthesia ; Extracorporeal Circulation ; Female ; Humans ; Intubation, Intratracheal ; Male ; Middle Aged ; Retrospective Studies ; Tracheal Stenosis ; surgery ; Tracheostomy ; Young Adult

Objective To express the beta hemolysin ( Hlb), an important toxin secreted by Staphylococcus aureus ( S.aureus) and the mutant protein Hlb H-149-N , to detect the hemolytic activity of Hlb and Hlb H-149-N on sheep erythrocytes , and to prepare the specific antibodies against Hlb which can inhibit the hemolytic activity of Hlb .Methods Hlb gene was amplified by PCR using S.aureus NCTC-8325 genome DNA as template.The expression vector pET-28a-hlb was constructed and transformed into E.coli BL21(DE3).The expression vector pET28a-hlbH-149-Nwas constructed through point mutation.The recombinant Hlb and Hlb H-149-N protein were expressed and purified by Ni 2+affinity chromatography .The hemolytic activity of Hlb and Hlb H-149-N was measured by sheep erythrocyte lysis assay .Results Recombinant Hlb protein and the mutant were obtained .Further investigations showed that Hlb could significantly induce the lysis of SRBC while HlbH-149-N could not.The specific polyclonal antibodies against Hlb (anti-Hlb) were prepared.It was found that anti-Hlb recognized Hlb and Hlb H-149-N .Moreover , it was found that anti-Hlb blocked the hemolytic activity of Hlb .Conclusion The recombinant Hlb protein with high hemolytic activity and Hlb H-149-N without hemolytic activity are obtained while its neutralized antibody is pepared .Hlb from S.aureus has different hemolytic effects on erythrocytes from various species .Our findings will facilitate the investigation on the role of Hlb in the pathogenesis of S.aureus.

Objective To investigate the function of transferrin-DNA complex,transported by transferrin(Tf)and trans-arterial injection via interventional approach be the duel-target-orientated delivery and the transferring into malignant cells to get more effective therapy.Methods p53-LipofectAMINE ligand with different concentrations of Tf(0,10,25,50,100?g)transfected the 4 strains including LM6、Hep3B、YY and L02 in vitro to evaluate the gene transfeetion efficiency through western blot.Then,after setting up the VX2 hepatocarcinoma models,we delivered the Tf-p53-LipofeetAMINE complex into the hepatic arteries via interventional techniques to analyse the transfection efficiency in vivo.Results Tf,within the range of 10 100?g,could increase gene transfection efficiency mediated by liposome,and the efficiency increases with the raise of Tf concentration.Combination with interventional technique to inject Tf-DNA complex into tumor arteries,gene transfeetion efficiency was enhanced in rabbit models.Conclusion Tf can enhance gene- liposome transfection efficiency,furthermore with combination of interventional catheter technique,there would be a potential duel-target-orientated gene therapy method.(J Intervent Radiol,2007,16:99-103)

Objective To investigate the effects of electromagnetic irradiation on activation of protein kinase C(PKC)and phosphorylation of glutamate receptor 2(GluR2)in rat cerebellum.Methods Sixty male Wistar rats were divided randomly into a control group and an electromagnetic exposure group(including 5 subgroups ob- served at different time points after the irradiation,eg.0 hour,3 hours,12 hours,24 hours and 72 hours after irradi- ation),with 10 rats in each group.All the rats in the exposure group were exposed to 90 mW/cm2 electromagnetic ir- radiation for 20 minutes,their rectal temperature was detected immediately after irradiation and the specific absorption rate(SAR)value was calculated,activation of PKC was detected with improved TaKai method,the level of cerebellar GluR2 expression and phosphorylation(ser880)was detected by using Western blot.Results Immediately(0 hour)after exposure,the rectal temperature of rats increased 2.99℃,SAR value was 8.66 W/kg.When compared to the control group,it was found that there was no significant difference between the exposure group and the control group with regard to all the parameters at 3,12,24 and 72 hours after exposure,except that the cerebellar PKC acti- vation and GluR2(ser 880)phosphorylation decreased significantly immediately after irradiation.Conclusion The electromagnetic irradiation has injurious effects on cerebellar signal pathway of for motor learning.

Many studies have shown that the incidence of type 1 diabetes mellitus (T1DM) is increasing with an annual of 2％ to 5％.As the same with type 2 diabetes mellitus,T1DM is also a risk factor for stroke.Although some T1DM studies have taken stroke as a component of the composite endpoint of cardiovascular events,a few studies have focused on the risk of stroke in patients with T1DM.Recent studies have shown that the risk of stroke in patients with T1DM is significantly higher than those without diabetes mellitus,especially in the population under the age of 50.In addition,the T1DM patients died of the risk of stroke are 3 to 4 times higher than the general population.This article reviews the relationship between T1DM and stroke.