OBJECTIVE：To prepare Azelnidipine enteric solid dispersion and evaluate its quality. METHODS ：Azelnidipine enteric solid dispersion was prepared by solvent method. Taking cumulative dissolution rate as the index ，single factor test was used to optimize carrier material type and its ratio. The quality of the product was evaluated by DSC ，XRD and FTIR ，and its stability was investigated. RESULTS ：After azelnidipine and carrier material of Eudragit L 100-55 acrylic resin were prepared to enteric solid dispersion at a ratio of 1∶5（m/m），its dissolution rate was significantly improved. DSC ，XRD and FTIR method had all verified the crystal form of azelnidipine changed and it existed in amorphous form. The results of stability test showed that Azelnidipine enteric solid dispersion was stable under high temperature （60 ℃），high humidity （75％）and strong light [ （4 500±500）lx] for 10 days. CONCLUSIONS ：Azelnidipine enteric solid dispersion by solvent method with Eudragit L 100-55 acrylic resin as carrier can eliminate the influence of crystal form ，improve dissolution and has good stability.

Through summarizing and analyzing a large number of documents and reports of large academic conferences in China, the current situation and the prospect of individualized drug delivery model were analyzed based on folate metabolic gene in pharmaceutical care. Folate metabolic genemethylenetetrahydrofolate reductase (MTHFR) C677T and methionine synthase reductase (MTRR) A66G were related with development of multiple diseases. Its polymorphism guidesindividualized drug administrationto increase the efficacy of drugs or decrease adverse effects.

OBJECTIVE:To establish the method for the determination of doxofylline in human serum. METHODS:Online two-dimensional column switching-HPLC was adopted to determine the concentration of doxofylline in human serum. First-dimensional chromatographic column was Waters C18column,and middle column was SC2. First-dimensional and second-dimensional column mobile phrase were methanol-water(70 : 30,V/V). The detection wavelength was 273 nm,and column temperature was 40 ℃. Sample volume was 10 μL. RESULTS:The linear range of doxofylline were 0.5-50.00 μg/mL(r=0.999 9), and the detection limit was 0.01 μg/mL. The quantitative limit was 0.5 μg/mL. RSDs of intra-day and inter-day were 1.51%-1.89%and 1.52%-1.92%(n=5). The accuracy were 97.91%-104.19%(n=5). Extraction recoveries rate were 91.63%-93.44%(RSD<2.00%,n=3). RSD of matrix effect were lower than or equal to 3.01%(n=6),and RSD of stability test was lower than 5.00%(n=6). After 3 patients were given intravenous injection of Doxofylline and glucose injection(0.3 g/d)up to steady state,the serum concentrations of doxofylline were 3.23,3.35,3.68 μg/mL before medication on the next day(RSD=2.28%,2.34%, 2.14%,n=5). CONCLUSIONS:The method is simple,rapid,accurate and suitable for the determination of plasma concentration of doxofylline.

Chronic gastritis (CG) is a common disease of digestive system. It is of the utmost importance to reply the animal mod-el of CG in the researches on pathogenesis,treatment mechanism and drugs development. It's necessary to review the general situation about the replication of CG animal model since there is no spontaneous animal model of CG. The research literatures related to the rep-lication of CG animal model in recent years were reviewed,all kinds of methods on the animal model replication were reorganized sys-temically,and a new classification was established. Furthermore,the model mechanism,precautions and success rate of each classifi-cation method were evaluated concisely,scientifically and objectively in order to exploit the research ideas of researchers and provide reference for further studies.

Objective: To make out the optimal drug treatment regimen through the participation of clinical pharmacists in the treatment of one case of child with renal abscess complicated with iron deficiency anemia.Methods: Clinical pharmacists participated in the design of treatment program for the child, including the choices of drugs, dosage and route, and the treatment of adverse reactions, in order to make out the individualized medication.Results: By selecting the sensitive antibiotics, the renal abscess caused by Escherichia coli was cured successfully.Conclusion: Clinical pharmacists participating in clinical consultation can further optimize the treatment plan, and play an active role in the treatment of infected patients.

Objective To discuss the evaluation method of anti-infective therapy by clinical pharmacist .Methods Anti-infection therapy for an AECOPD patient in department of respiration in our hospital was analyzed to discuss the evaluation method of anti-infective therapy .Results The patient had indication to use antibacterial ,and combination of Amikacin and Piperacillin-sulbactam were selected as initial empirical treatment for common respiratory G --bacilli including drug resistant of Pseudomonas aeruginosa ,which was rationality .But the whole process of using the initial combination linked to the hospital was unreasonable .Conclusion To evaluate the rationality of anti-infection treatment ,the indication to use antibacterial need to be determined firstly ,and combined with the severity of the patient ,prior treatment ,etiology of the site of infection ,and choice of antibiotics to evaluate the rationality of initial empiric regimen secondly .For etiology positive results ,the efficacy of initial empiric therapy ,interpretation of etiology results and the clinical significance ,guidelines recommend should be com-bined ,following-up selection of drug to evaluate the rationality of follow-up treatment .

Objective To investigate the effect of small direct‐current electrical stimulation on migration and invasion related MMPs/TIMPs expression of trophoblast cells .Methods The trophoblast cells were exposed to the direct current electrical field at 150 mV/mm for 5 and 10 hours .Cell images were recorded with continuous photographing and analyzed by image analyzer .The ex‐pression levels of MMP2 ,MMP9 ,TIMP1 and TIMP2 were measured using quantitative RT‐PCR and Western blot .Results In non‐electrical field culture trophoblast cells migrated slowly with random directions .Trophoblast cells cultured in media containing 10% calf serum with the application of 150 mV/mm direct current electrical stimulation ,showed marked cathodal migration (P<0 .01) ,the cell body stretched ,perpendicular to the direction of the electric field .Compared with the non‐electrical field stimulation controls ,trophoblasts under the electrical field stimulation had the increased MMP2 mRNA and protein expression (P< 0 .05) , while MMP9 ,TIMP1 and TIMP2 had no obvious changes of mRNA or protein expressions .Conclusion Physiological direct‐cur‐rent electrical fields might induce directed migration and perpendicular orientation of trophoblast cells .The enhanced MMP2 expres‐sion may play an important role in the migration and invasive activity of trophoblast cells in small electrical field .

Objective To investigate the application value of fetal umbilical cord blood hemoglobin analysis in the prenatal diag ‐nosis of thalassemia .Methods 113 couples were the carriers of the same gene type of thalassemia ,moreover the females were in the pregnant period of 24 - 30 pregnant weeks and performed the prenatal diagnosis .The fetal umbilical cord blood hemoglobin compo‐nents were analyzed by the full automatic capillary electrophoresis technique ,meanwhile the fetal thalassemia gene was detected .Re‐sults Among 113 fetuses ,the umbilical cord blood HbBart′s level in 11 cases of severe α thalassemia was 85 .0% - 95 .5% ,which in 9 cases of intermediate type α thalassemia was 22 .0% - 39 .5% ;the umbilical cord blood HbA level in 6 cases of severe β thalas‐semia was 0% - 0 .4% ,which in 17 cases of light type β thalassemia was 2 .1% - 12 .5% .Conclusion The fetal umbilical cord blood hemoglobin analysis could be used for rapid prenatal diagnosis of severe α ,β and intermediate type α thalassemia ,which can serve as a supplementary method for the prenatal diagnosis of thalassemia .

OBJECTIVETo explore the formation of pre-metastatic niche in the mouse lung and to study the underlying molecular mechanisms whereby primary breast carcinoma-derived factors mediate recruitment of bone marrow-derived cells (BMDCs) and affect the formation of pre-metastatic lung environment before the arrival of tumor cells.

METHODSMammary carcinoma 4T1 cells were inoculated into the mammary gland to construct mouse model of breast cancer. Confocal microscopy was used to detect the recruitment of BMDCs in the pre-metastatic lungs. The expression of factors in the mouse sera and 4T1 cell culture media was assayed using RayBio Custom mouse cytokine antibody array kit. The mice were injected daily with recombinant VEGF for 7 consecutive days to observe the effect of VEGF on BMDCs recruitment in the mouse lung.

RESULTSNo BMDCs were observed in the lungs of control and 4T1-tumor-bearing mice on day 0. On day 7 and 14, clusters of BMDCs observed in the lungs of 4T1-tumor-bearing mice were 8.7±2.2/objective field and 48.8±3.2/objective field, respectively, significantly higher than those in the control mice (1.1±0.8/objective field and 3.1±1.7/objective field) (P<0.05 for both). Confocal microscopic observation found that metastatic breast cancer cells preferentially facilitate BMDCs recruitment sites in the pre-metastatic mouse lungs. The levels of VEGF, GM-CSF, and IL-6 in the serum of 4T1-tumor-bearing mice were significantly increased compared with those in the control group (P<0.05 for all). However, VEGF was detected only in the culture media of 4T1 cells. The amount of BMDCs in the mouse lung tissue was (22.8±3.6)/objective field in the VEGF group and (3.1±0.4)/objective field in the control group (P<0.05). There were 36.8±5.4 metastatic foci in the lung tissue of VEGF group and 12.6±2.2 in the control group (P<0.05).

CONCLUSIONSThe results of this study demonstrate that primary breast cancer cells can alter the lung microenvironment during the pre-metastatic phase and induce the formation of pre-metastatic niche. Primary tumor cell-derived VEGF may be a crucial factor responsible for the formation of pre-metastatic niche.

Animals ; Bone Marrow Cells ; Breast Neoplasms ; metabolism ; pathology ; Cell Line, Tumor ; Disease Models, Animal ; Female ; Granulocyte-Macrophage Colony-Stimulating Factor ; blood ; Humans ; Interleukin-6 ; blood ; Lung ; pathology ; Lung Neoplasms ; secondary ; Mice ; Recombinant Proteins ; administration & dosage ; Time Factors ; Tumor Microenvironment ; Vascular Endothelial Growth Factor A ; administration & dosage ; physiology ; secretion

OBJECTIVE:To study the effects of Yupingfeng powder on immune function of rats with lung-qi deficiency syn-drome. METHODS:60 SD rats were randomly divided into normal group,model group,positive group [Renshen beiqi tablet 0.6 g (crude drug)/kg] and Yupingfeng powder high-dose,medium-dose and low-dose groups [24,12,6 g (crude drug)/kg],with 10 rats in each group. Except for normal group,those groups were given SO2+comprehensive cold stimulation to induce lung-qi defi-ciency syndrome model. After modeling,treatment groups were given relevant drug solutions intragastrically,and normal group and model group were given constant volume of normal saline intragastrically,once a day,for consecutive 13 d. After administra-tion,serum levels of IL-3 and IL-6,the proportion of CD3+,CD4+,CD8+in T lymphocyte were determined,and pathological chang-es of lung and bronchus were observed. RESULTS:Compared with normal group,serum levels of IL-3 and IL-6 and the propor-tion of CD8+ in T lymphocyte increased significantly in model group,while the proportions of CD3+ and CD4+ in T lymphocyte and the ratio of CD4+/CD8+ decreased(P<0.01);obvious lung and bronchus injury and inflammatory reaction were observed. Compared with model group,serum level of IL-3 decreased significantly in positive group and Yupingfeng powder high-dose group;serum level of IL-6 and the proportion of CD8 + in T lymphocyte decreased significantly in positive group and Yupingfeng powder high-dose and medium-dose groups,while the proportion of CD3+ in T lymphocyte increased significantly;the proportion of CD4+and the ratio of CD4+/CD8+increased significantly in treatment groups(P<0.05 or P<0.01);lung and bronchial injury,and inflam-mation reaction were relieved. CONCLUSIONS:Yupingfeng powder can enhance immune function of rats with lung-qi deficiency syndrome.