Objective:To evaluate curative impact of booster immunization with paternal lymphocytes on recurrent spontaneous abortors(RSA)with less reaction of primary patermal lymphocyte immunization.Methods:RSA patients with insufficient materno-fetal immuno-recognition were selected by flow cytometry of blocking antibody analysis and immunized with either induced paternal lymphocytes pretreated by IFN-? in vitro to those of anti-CD3-BE and anti-CD4-BE Ab lower than 0% or direct intradermal vaccination with their paternal lymphocytes without IFN-? pretreatment to those of anti-CD3-BE Ab beyond 0%.Reassessment of blocking antibodies was performed at the end of the second immnunization course.Results:Levels of blocking antibodies were significantly raised after the secondary booster immunization in RSA with insufficient materno-fetal immnuno-recognition whose blocking antibodies continuously decreased after being treated by the primary paternal lymphocyte immunization.No improvement of parameters was observed except the blocking effect in patients receiving secondary direct intradermal vaccination treatment.Conclusion:It is necessary for the RSA with insufficient materno-fetal immuno-recognition to experience secondary booster immunization preferably with paternal lymphocytes pretreated by IFN-? in vitro.

Objective To establish a sensitive, rapid and simple high-performance liquid chromatography (HPLC) method for the determination of amphotericin B (AraB) and itraconazole (ITZ) in human cerebrospinal fluid (CSF). Methods Solid-phase extraction (SPE) was involved in sample preparation in this method, followed by reverse-phase separation under two different chromatographic systems. Results The tinearity for both AraB and ITZ ranged from 5 ng/mL to 100 ng/mL and the inter-day and intra-day RSD were both below 7.6% at the concentrations of 20,50 and 100 ng/mL. Conclusions The method we established has been applied to the therapeutic drug monitoring on cryptococcal-meningitis-infected patients who were given comedication of these two drugs.

Objective:To investigate the protective effect of schisandrin B (SchB)on the cerebral ischemia reperfusion injury of the rats and the influence in HSPA12B/PI3K/Akt signaling pathway,and to explore the mechanisms.Methods:130 SD rats were divided into sham group,cerebral ischemia reperfusion injury model group (model group),low dose of SchB group (SchB 3 mg· kg-1 ,SchB1 group),middle dose of SchB group (SchB 10 mg·kg-1 ,SchB2 group)and high dose of SchB group (SchB 30 mg·kg-1 ,SchB3 group)(n=26).The rats in sham group didn’t plug lines;the rats in model were used to establish ischemia reperfusion models;the rats in SchB1 ,SchB2 and SchB3 groups were firstly pretreated with different doses of SchB for 7 d,and then they were used to build cerebral ischemia reperfusion injury models.The nerve dysfunction of rats was evaluated by neurologic deficit score.The cerebral edema was detected by measuring the content of water in brain tissue.The morphological changes of brain tissue were observed by toluidine blue staining.The levels of nuclear factor kappa B (NF-κB), tumor necrosis factor-α(TNF-α),interleukin-1 (IL-1)and interleukin-6 (IL-6)in the brain tissue were detected by ELISA.Western blotting method was used to detect the protein expression levels of heat shock protein A12B (HSPA12B ), serine-threonine kinase (Akt ) and phosphorylation serine-threonine kinase (p-AKT ). Results:Compared with sham group,the neurologic deficit score of rats in model group was significantly increased (P <0.01),and the content of water in brain tissue was increased (P < 0.01 );the brain tissue structure was loosened,and the mesenchyme appeared edema;the NF-κB,TNF-α,IL-1,and IL-6 levels were increased (P <0.01),and the expression levels of HSPA12B and p-Akt proteins were decreased (P <0.01).Compared with model group,the neurologic deficit scores of the rats in SchB1 ,SchB2 ,and SchB3 groups were decreased (P <0.01),and the contents of water in brain tissue of the rats in SchB2 and SchB3 groups were decreased (P <0.05);the edema of nerve cells was alleviated,and the cavities were reduced;the NF-κB,TNF-α,IL-1,and IL-6 levels were decreased (P <0.05 or P <0.01),the expression levels of the HSPA12B protein in SchB2 ,and SchB3 groups were increased (P <0.05),and the p-Akt protein expression levels of the rats in SchB1 ,SchB2 ,and SchB3 groups were increased (P <0.01).Conclusion:SchB could protect the cerebral ischemia reperfusion injury of rats,its mechanism may be related to regulating the HSPA12B/PI3K/Akt signaling pathway and inhibiting the inflammatory reaction damage to the nerve cells of reperfusion.

Clinical internship is for bachelor students to learn how to integrate theories in textbooks with clinical practice.Clinical pharmacist training is for pharmacists to obtain and enforce the capability of rational use of drugs.These two are at the different stages of clinical pharmacist cultivation mode.They are different in teaching nature,goal and students' background.The necessity of clinical internship bridged to clinical pharmacist training is discussed in this paper and after the convergence,the teaching design of chnical internship program bridged to the training is characterized by basic education which focuses on basic theories,knowledge and skills of clinical medicine and clinical pharmacy relevant to a certain common disease.The optimized internship program will work as a good foundation for students to face the challenges of clinical pharmacist training after graduation from school.

With the development of natural products, the research activities on the solubilization methods of water-insoluble natural products have been carried out worldwide. Big molecular weight and poor solubility of most natural active ingredients lead to a very poor oral absorption and low bioavailability, which has extremely limited their development in pharmaceutical fields and clinical application. As a result, it is necessary to find out a suitable technique to improve the solubility and enhance the oral bioavailability of insoluble natural drugs. Based on the related references published in these years, this review introduced some new techniques to improve the solubility and bioavailability of natural drugs, including prodrugs, inclusion complex, solid dispersion, cocrystals, osmotic pump, liquisolid compacts, micronization, self-microemulsifying, nanosuspensions, lipsomes, polymeric micelles and so on, and summarized the theory, characteristics, application range, application examples, problems and development direction of each technique.
Administration, Oral ; Biological Availability ; Biological Products ; administration & dosage ; chemistry ; pharmacokinetics ; Chemistry, Pharmaceutical ; methods ; trends ; Solubility ; Technology, Pharmaceutical ; methods ; trends ; Water

Objective To investigate the change of the intestinal permeability,the expression level of intestinal trefoil factor (ITF) mRNA and the relationship between them after total body irradiation (TBI),and explore the effect of TBI on the development of intestinal permeability and the expression level of ITF mRNA.Methods Twenty two BALB/c mice were randomly divided into 4 equal groups: 3 groups at 4,8 and 12 d after TBI with the total dose of 8.0 Gy and the dose rate of 1.0 Gy/min respectively,and a control group.Lactulose (L) and mannitol (M) were perfused into the esophagus before the experiment and urine samples were collected.Liquid chromatography was used to measure the L/M excretion ratio in the urine samples collected 4,8,and 12 days after the TBI.And then the mice were killed with their intestine were taken out.The expression of ITF mRNA in the jejunum tissue was detected by real-time fluorescence quantitative PCR.Results The urine L/M ratio levels of the groups 4,8 and 12 days after TBI were (0.5092 ± 0.0352),(0.7174 ± 0.0116),and (0.7295 ± 0.0533) respectively,all significantly higher than that of the control group [(0.2908 ± 0.0533),F = 321.47,P ＜ 0.05].The ITF mRNA expression levels of groups 4,8 and 12 days after TBI were (0.78612 ±0.1428),(0.2521 ±0.1223),and (0.2306 + 0.0221 ) respectively,all significantly lower than that of the control group [( 1.3498 + 0.0476),F = 235.71 ,P ＜ 0.05].The urine L/M ratio was significantly negatively correlated with the expression of ITF mRNA in all TBI groups (r = - 0.985,P ＜ 0.01 ).Conclusions The intestinal permeability increases and the expression level of ITF mRNA decreases after TBI.The urine L/M ratio is negatively correlated with the expression level of ITF mRNA after TBI.ITF is involved in protection against intestinal permeability induced by TBI.

Objective To study the resistances of CDl33 + subset purified from gastric cancer cell line to chemotherapy drugs and the mechanism of this resistance regarding to the mRNA expressions of both Bcl-2 and BAX in relation to the relative apoptotic genes.Methods CD133 + subset and CD133-subset were purified from KATOⅢ cell linc by magnetic activated cell sorting.The proliferating ability of these two subsets resistantnt to 5-FU,Cisplatin(DDP,PDD) and Etoposide was checked and compared by CCK-8 test.The apoptotic changes of these two subsets regarding to the expression of mRNA of both Bcl-2 and BAX were also analized by RT-PCR.Results In CD133 + subset,the contant percentage of CD133 + expression rate was 90％ via analysis of flow cytometye.Twelve hours after treatment of5-FU,DDP and VP-16,the cells in both CD133 + subgroup and CD133-subgroup would gradually start to change in apoptotic morphology.The growth inhibiting rate by CCK-8 measurement for 5-FU,DDP and VP-16 groups in CD133 + subgroup was significantly lower than that in CD133-subgroup.The data under different treatment respectively was,5-FU:(30.56 ± 1.99) ％-(88.60 ± 1.95) ％ vs (32.81 ± 2.67) ％-(95.73±2.12)％,P=0.045,cisplatin:(45.89 ±3.64)％-(81.20 ± 1.18)％ vs (50.21 ±3.22)％-(90.46±1.89)％,P=0.043,VP-16:(37.21 ±3.80)％-(78.49 ±3.22)％ vs (35.55 ±3.23)％-(89.32 ±-3.54) ％,P =0.048).After treatment of these three kind of anti-tumour drugs,the expression level of Bcl-2 mR-NA decreased significantly and the expression level of BAX mRNA increased significantly in both CD133 + subgroup and CD133-subgroup.However,these changing ranges of Bcl-2 mRNA and BAX mRNA were more obvious in CD133 + subgroup in comparison with those in CD133-subgroup.Conclusions In some degree,resistent potentiality of CD133 + cells to 5-FU,DDP and VP-16 has been identified,which may probably be due to the up-regulation of the expression of BAX and down-regulation of the expression of Bcl-2.

Objective　To study the diagnosis, treatment and prognosis of hepatolithiasis combined with cholangiocarcinoma. Methods　The clinical, pathological and follow-up data of 17 cases of hepatolithiasis combined with cholangiocarcinoma were retrospectively analysed. Results　The results showed that the incidence of cholangiocarcinoma in hepatolithiasis was 5% in this series. 17.6% of the patients were diagnosed as cholangiocarcinoma preoperatively. Tumor occurring in intrahepatic ducts was 88.2% and in hepatic porta ducts 11.8%. Nine cases were well-differentiated adenocarcinomas. Only 7(41.2%) cases were radically resected and their average survival time was 26.0 months. Eight(47.1%) patients underwent internal drainage with average survival time 12.4 months. 2(11.7%) cases subject to external drainage with survival time 3.6 months. Conclusions　If patients with hepatolithiasis have a long history of recurrent cholangitis, weight-loss in a short period, progressive jaundice or intractable abdominal pain, the possiblility of combined with cholangiocarcinoma should be considered. Resection of the tumor has a better prognosis than that of tumor unresected; and the prognosis of internal drainage is better than that of external drainage.

Objective: To observe the therapeutic action of earth enteral nutrition after jejunum interposition in patients with carcinoma of gastric cardia.Methods: Sixty-two patients after jejunum interposition were divided into early enteral nutrition group(n=33) and parenteral alimentation group(n=29).The clinical observation index and nutrition index were compared between the two groups.Results: The enteral nutrition group had more advantages than the parenteral alimentation group in the aspects of clinical observation index postoperative complication and nutrition index.Conclusion: Early enteral nutrition could improve gastrointestinal function and nutritional state and decrease the incidence rate of postoperative complication.

Objective To study the clinical,pathological characteristics and diagnosis of multiple system atrophy(MSA).Methods Among 4 cases of MSA,2 of them were from clinical data,the other 2were frum pathological data.Two cases verified by autopsy were investigated using Hematoxylin-eosi,Kltiver.Barrera and Gallvas-Braak silver staining and confirmed by immunohistochemistry using ubiquitin,α-synuclein staining.Results All 4 patients were male.aged 51-76.Case No.1 wag diagnosed as Parkinson's svndrome.Case No.2 was diagnosed as spinal ataxia cerebella,and the other two eases were diagnosed as MSA.The following changes were found by pathological studies.Macroscopic atrophies were presented in pens and cerebella.as well as putamen,globus pallidus and substantia nigra.Cerebral ventricles were dilated.Neuronal lOSS and gliosis could be seen at cerebral cortex.nigrostriatal.globus pallidus,pontine nuclei,subslantia innominata,inferior olives,doral motor nucleus of vagus,cerebellum antl intermediolateral column of the spinal cord.In the white matter of these regions cytoplasmic inclusions bodies were extensively present in oligodendrocytes.Conclusions Olivopontocerebellar atrophy mainly shows the,clinical symptoms of pens,cerebellum,and autonomic nerves damage;Shy-Drager syndrome presents mainly with the erecting hypotenstion symptom,while striatonigral degeneration mainly involves extrapyramidal system.As these three diseases share the common basic pathological changes,they are preferred to be classified as the subtype of MSA.