As the economy develops rapidly and the medical care system is being reformed continuously in China,the patient-centered mode of Pharmacy custody and the Clinical Pharmacy based on rational medicine have become the main work of pharmacy in hospitals in the new epoch.However,because of the lag of Clinical pharmacy education in our country,there is a shortage of the qualified clinical pharmacists,which restricts the transformation of the mode of pharmacy in hospitals.So to conform to the trend of international pharmaceutical science,it is necessary to set the clinical pharmacy program to train clinical pharmacists,quicken the education of clinical pharmacy and promote the development of pharmacy.

Objective: To enhanced the physical stability of adenovirus vectors(Adv) and ablated humoral immune responses by PEGylation of adenovirus with polyethylene glycols.Methods: PEGylated Adv(PEG-Adv) was constructed by PEGylated adenoviral capsid proteins with activated methoxypolyethylene glycols,and gene expression was evaluated using A549 cells.Furthermore,the plasma half life and the antibody evasion ability were also evaluated.Results: PEG-adv could be protected from antibody neutralization in the high antibody titers to adenovirus,suggesting that PEGylation improve of the ability to administer Adv on a repeated basis.Conclusion: PEGylated Adv can maintain strong protective activity against antibodies.The approach described here could form the basis for further development of adenoviral gene therapy vectors with improved pharmacokinetics and increased efficiency of therapeutic gene transfer in disease.

Objective: In the present study,We developed and assess an integrin-targeted fiber-mutant Ad vector containing the Arg-Gly-Asp(RGD) peptide motif on the fiber knob for the transfection of melanoma cell lines.Methods: We constructed RGD-Adv by in vitro ligation method,and investigated the efficiency of gene transdution in melanoma cells,studied its stability,in vitro,and in vivo toxicology.Results: For in vivo and in vitro,gene transfer the RGD-Adv more efficient than the vector containing wild type fiber via an CAR independent cell entry pathway.Conclusion: These results revealed that gene delivery by RGD-Adv was more efficient than that by conventional Adv and suggest that av-integrin-targeted Adv will be of great utility for gene therapy and gene transfer experiments.

Objective To study the stability and reproducibility in serum proteome by matrix assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS).Methods Bruker Daltonics MALDI-TOF-MS was adopted under the linear mode, with mass ranging from 800 to 10 000 m/z.MB-WCX pre-extraction kit and Clinprotools software was used to analyze data.Results The reproducibility study was carried out under the standardized conditions.Data analysis showed that the m/z ratio was in the acceptable range, and the coefficients of variation(CV) was 12.7% ,13.1% and 18.8% ,respectively in the parallel experiment by taking 2 cancer and 1 healthy control serum samples and could identify the diseased samples.Then 30 healthy control samples were used to validate this result, all of which showed very good mass profile. The average CV was 25.5%, which could meet the requirements of clinical laboratory.Conclusion With the help of optimized experimental conditions and MALDI-TOF-MS, stable and reproducible mass spectrum can be required which is helpful for the early diagnosis of diseases.

Acute organophosphorus pesticides poisoning(AOPP)is one of the common critical emergency problems and the fatality is extremely high. Organophosphorus pesticides(OPS)are highly effective acetylcholinesterase(AChE)inhibitors. The AChE inhibition results in accumulation of acetyl?choline and overestimation of acetylcholine receptors in synapses of the autonomic nervous system, central nervous system,and neuromuscular junctions,causing a series of symptoms including musca?rinic,nicotinic,and central nervous system dysfunctions. In the early stage of AOPP,the core treat?ment is the use of anticholinergic drugs coupled with cholinesterase reactivator. Atropine and penehycli?dine hydrochloride(Tuoning)are the most commonly used anticholinergic drugs,which can effectively compete with acetylcholine receptors,block the effect of acetylcholine,and relieve the symptoms of re?spiratory failure,bronchospasm,pulmonary edema caused by AOPP. Oximes are believed to function as AChE reactivators,that can promote enzymatic reactivation and restore the activity of hydrolysis of ace? tylcholine. Recently,new avproaches,such as intravenous lipid emulsion,new detoxification drugs, blood purification,and traditional Chinese medicine,have attracted more attention. Overall,great prog?ress has been made in AOPP treatments. A better understanding of AOPP mechanism,and the support from pharmacology,toxicology,and related fields can contribute to the treatment of AOPP. Improved medical management of AOPP can also result in fewer deaths from poisoning worldwide.

Objective To investigate the changes of serum and pleural effusion inflammatory indexes in chil-dren with mycoplasma pneumoniae complicated with pleural effusion.Methods Enzyme linked immunosorbent assay (ELISA)double antibody sandwich method was used in the three of pleural effusion group,mycoplasma pneumonia group,control group and other groups to detect serum and pleural effusion human interleukin 6 (IL -6).human inter-leukin 2 (IL -2)and TNF -(human tumor necrosis factor alpha)etc.Inflammation index levels were detected and compared.Results The group of patients with mycoplasma pneumonia mycoplasma pneumonia patients was (9.93 ± 1.05)pg/mL for the IL -6 level,IL -2 levels for (4.93 ±0.55)μg/mL,(1.45 ±0.17)ng/mL for the TNF alpha level,which were significantly higher than those of the control group,the IL -2 was significantly lower than that of the control group,with statistically significant difference (t =6.25,5.88,4.63,5.95,3.69,5.95,all P <0.05).Compa-ring pleural effusion group and mycoplasma pneumonia group,we found serum IL -6,TNF alpha levels of pleural effu-sion group were significantly higher than that of mycoplasma pneumonia group,while IL -2 was lower than that in group mycoplasma pneumonia,with statistically significant difference (t =4.02,3.06,3.06 and 2.88,all P <0.05). The levels of serum IL -6,IL -2 and TNF -in the serum of patients with different effusion levels were significantly different from the other two groups (all P <0.05).Pleural effusion IL -6 and TNF level of pleural effusion group and mycoplasma pneumonia patients was significantly higher than those of the control group and IL -2 were significantly lower than that of the control group,the difference had statistical significance (t =5.69,3.69,602,4.11,2.94,3.67, all P <0.05).Pleural effusion pleural effusion IL -6 and TNF levels were significantly higher than those in the myco-plasma pneumonia group and IL -2 were significantly lower than that in mycoplasma pneumonia group,the difference had statistical significance (t =3.58,4.13,3.21,all P <0.05).The inflammatory indexes of patients with different effusion volume could be found in the pleural effusion,in patients with a large number of pleural effusion,the IL -2, IL -6 and TNF -levels compared with the other two groups showed significantly different (t =6.11、5.44、4.82,all P <0.05).Conclusion IL -6,IL -2 and TNF alpha in the occurrence and development of mycoplasma pneumoniae pneumonia play an important role.Suffering from mycoplasma pneumonia in patients with pleural effusion,whoseTNF-and IL -6 inflammatory index and serum indexes are abnormal,is of certain clinical practical value for clinical diagnosis,treatment and prognosis,as the indicator of the development and prognosis of pneumonia and pleural effusion.

Objective To explore the etiology of patients with chief complaint of vertigo in the department of neurology in order to reduce thc rate of misdiagnosis.MethodsA total of 367 patients with chief complaint of vertigo in our department of neurology were followed up.The associated medical history,symptoms and physical examination were obtained.ResultsThe main diagnoses for the 367 patients were benign paroxysmal positional vertigo (BPPV) ( 219,59.7％ ),posterior circulation ischemia (PCI) ( 65,17.7％ ),migraine ( 31,8.4％ ),hypertension ( 18,4.9％ ) and psychogcnic vertigo ( 17,4.6％ ).Conclusions Presentation of vertigo can be clinically diagnosed in most discases,with the most common causc of BPPV.Combination of the prominent clinical features,physical examinations and especially Dix- Hallpike maneuver may guide the general physicians to a most proper cause of vertigo.

Objective To investigate the value of early hematocrit (Hct) level in predicting early neurological deterioration (END) in patients with acute ischemic stroke. Methods The patients with acute ischemic stroke within 24 h of onset were enrolled prospectively. They were divided into low Hct, normal Hct, and high Hct according to the quantile of the measured Hct. END was defined as an increase of ≥2 of the National Institute of Health Stroke Scale (NIHSS) score or ≥1 of the motor item score within 5 d after admission compared with the baseline. The vascular risk factors, clinical features, baseline NIHSS score, infarct size, and laboratory test variables were compared between the END group and the non -END group. Multivariate logistic regression analysis was used to identify the independent risk factors for END. Results A total of 216 patients with acute ischemic stroke were enrolled, including 128 males (59.26%). Their mean age was 67.40 ±14.12 years. Sixty-two patients (28.70%) experienced END. The normal ranges of Hct in male and female were 40.12%-46.35% and 38.32%-44.17%, respectively. Univariate analysis indicated that there were significantly differences in baseline NIHSS score ( P =0.001), fasting glucose (P =0.030), C reactive protein (CRP) (P =0.041), and the proportions of different Hct levels between the END group and the non-END group (P =0.023). The END incidences in patients with high -level Hct (40.0%) and low –level Hct (35.2%) were significantly higher than that in the normal Hct patients (20 .4%), but there was no significant difference between the high-level and low -level Hct patients ( P = 0.690). Multivariate logistic regression analysis showed that theigh-level Hct (odds ratio 2.460, 95% confidence interval 1.146-5.283; P =0.021) and the baseline NIHSS score (odds ratio 1.070, 95% confidence interval 1.014-1.129; P = 0.013) were the independent risk factors for END. Conclusion The elevated Hct in patients with acute ischemic stroke are susceptible to END.

Objective To explore a new method for establishing an animal model of cochlear ischemia.Methods Thirty guinea pigs were randomized into three groups:normal group,operation group,ischemia group.Anterior inferior cerebellar artery(AICA)was exposed surgically via a skull base approach.In ischemia group,a small piece of filter paper containing FeCl3 was placed upon the AICA to induce thrombus formation.In operation group,AICA was only exposed.In normal group,nothing was done to animal.The blood flow of cochlea(CoBF)was continuously monitored with laser Doppler flowmeter.The thresholds of auditory brainstem response(ABR)were measured before,after each experiment,and one week after operation.The AICAs of ischemia group and operation group were resected and pathological sections were perfomed for observation of the details.Results After the administration of FeCl3,the CoBF decreased to 50% of the base level at 30 min.In the AICA pathological sections of ischemia group,white thrombus composed of cellulose,blood platelets and erythrocytes could be seen.The threshold of ABR in ischemia group increased significantly.Conclusion The method provides a relatively ideal model for ischemis of the inner ear and this model may be helpful in studying the mechanisms of hearing loss caused by chronic microcirculatory disorders.

OBJECTIVE: To characterize the pharmacokinetics of mildranate after a single dose intravenous infusion of 250, 500 and 1000 mg in healthy subjects, and to assess the dose proportionality of mildranate over the potential therapeutic dose range of 250-1000 mg. METHODS: In a randomized three-way crossover study, twelve healthy subjects were given a single dose intravenous infusion of mildranate of 250, 500, and 1000 mg. Plasma concentrations were determined at selected time points for 24 h. The pharmacokinetic parameters were calculated by DAS software. RESULTS: The elimination half-life of mildranate after iv of 250, 500, and 1000 mg was about 5-6 h, and the peak plasma concentration (ρmax) increased linearly from (11.70±1.49) to (43.60±6.91) μg·mL-1 with increasing dosages. Moreover, the area under the plasma concentration vs time curve (AUC) increased linearly within the dose range of 250-1000 mg. The urinary excretion rate were (30.19±7.63)%, (39.64±5.02)% and (58.10±10.21)%, respectively. CONCLUSION: Mildranate exhibits a linear pharmacokinetic profile in the dose range of 250-1000 mg. Dose-dependent parameters(ρmax and AUC) increase in an approximately dose-proportional manner. There are significant differences in tmax and urinary excretion rate in the different dose groups. The differences in the pharmacokinetic parameters (tmax, ρmax, t1/2, AUC0-t, CL, Vd, MRT0-t, and urinary excretion rate) between genders are not statistically significant, but the difference in urinary excretion rate at 500 mg was statistically significant.