OBJECTIVE:To provide reference for improving the quality of clinical pharmacy undergraduates in our university. METHODS:Considering about the practice problems of clinical pharmacy undergraduates in our university,pilot reform was con-ducted in the First Affiliated Hospital of our university in respects of teacher arrangement,department rotation assignment,assess-ment method. RESULTS:For new practice mode,in term of teacher arrangement,when the students were practicing in clinical pharmacy department,they were taught by clinical doctors and pharmacists;teacher training should be strengthened,and a variety of teaching methods was carried out. In term of department rotation assignment,to shorten the practice time of basic pharmacy de-partment,and increase the clinical pharmacy practice department and practice time;to integrate the content of clinical medicine and clinical pharmacy practice,and select clinical medical departments equipped with clinical pharmacists to practice. In term of assess-ment method,there were 3 aspects including clinical pharmacy practice skills assessment,drug-related theory examination and ba-sic situation assessment during internship. CONCLUSIONS:The new practice mode focuses on clinical pharmacy application skills training and students practical skills assessment,contributes to cultivate students'thinking of rational drug use and improves clini-cal practice skill of students. It is suitable for clinical pharmacy undergraduate internship of our university.

OBJECTIVE:To study the targeting of folic acid(FA)-modified docetaxel(DOC)nano-liposome(L-DOC-FA)to hepatocellular carcinoma Bel-7402 cells in vivo and in vitro. METHODS:The cell viability and survival rate of Bel-7402 cells was tested by CCK-8 kit after treated with 0,1,2,5,10 and 20 μg/ml DOC,L-DOC and L-DOC-FA for 24 h. And then,the fluores-cein isothiocyanate was used to label L-DOC and L-DOC-FA nano-liposome,and the rate of L-DOC and L-DOC-FA absorbed by hepatocellular carcinoma Bel-7402 cells were detected. 125I was used to label L-DOC and L-DOC-FA nano-liposome,and then the contents of them in the subcutaneous tumor tissues were detected. 28 Balb/c naked mice were selected and given liver cell suspen-sion via back ih to induce tumor model. After modeling,naked mice were divided into blank control group(normal saline),DOC group(3 mg/kg),L-DOC(3 mg/kg,by DOC)and L-DOC-FA(3 mg/kg,by DOC). They were given relevant medicine intrave-nously once a day for consecutive 30 d. The relative tumor volume in naked mice was detected. RESULTS:DOC,L-DOC and L-DOC-FA all inhibited the cell viability of Bel-7402 cells,the survival rate of cells decreased in concentration-dependant manner;compared with DOC and L-DOC,the cell viability decreased after treated with L-DOC-FA,the survival rate of cells decreased (P<0.01). The rate of L-DOC and L-DOC-FA absorbed by Bel-7402 cells in descending order as L-DOC-FA(69.5%)>L-DOC (31.2%),with statistical significance (P<0.01). The content of L-DOC-FA in tumor was significantly more than that of L-DOC (P<0.01). In addition,3 mg/kg L-DOC-FA showed better inhibitory effect than 3 mg/kg L-DOC and DOC on tumor,and the rela-tive tumor volume was smaller(P<0.01). CONCLUSIONS:L-DOC-FA has obvious targeting to Bel-7402 cells in vivo and in vi-tro,and shows good inhibitory effect on tumor in vivo and in vitro.

Using the enterprise resource planning(ERP)management mode,the paper analyzed the present medical insurance payment audit accounts at public hospitals,and probed into the establishment of an information management platform for medical insurance payment audit accounts in the ERP environment.The purpose is to perfect the management of medical insurance payment audit accounts,increase the efficiency of hospital's working capital,strengthen the quality and efficiency of hospital management.

Objective:To explore the effect of different hemoperfusion times on the recovery of serum cholinesterase (ChE) in patients with severe acute oral organophosphorus pesticide poisoning (AOPP).Methods:This was a retrospective case-control study. Patients with severe AOPP admitted to our hospital were identified between January 2010 and December 2019. The clinical information of patients with severe AOPP was collected between January 2010 and December 2019, the patient's ChE vitality levels were collected on admission, at 1, 3 and 5 days after admission, and the sex, age, oral poison volume, and related treatments were recorded as well. The relationship between ChE, different HP treatment times and patients without HP treatment was analyzed by generalized estimation equations and multiple comparisons afterward.Results:A total of 159 patients with severe AOPP were included in our study. Among them, 60 (37.74%) patients were male and 99 (62.26%) were female, with a median age of 33 years old (range 13-75 years old). The median oral dose of OPs was 75 mL (range 15-500 mL). Multivariate analysis results showed that in the unadjusted generalized estimation equation, compared with patients without HP treatment, the average ChE value of patients with single HP treatment was 745.6 U/L higher (95% CI: 467.09 - 1024.1; P<0.01), the average ChE value of patients with 2 times HP treatment was 565.81 U/L higher (95% CI: 384.25-747.36; P<0.01), and the average ChE value of patients with 3 times HP treatment was 43.86 U/L higher (95% CI: 420.71-1 067.01; P<0.01), the differences were all statistically significant. After adjusting the amount of oral OPs at admission, age and PSS score in the multiple generalized estimation equations, the results showed that whatever single HP treatment or multiple HP treatment, the recovery rate of ChE was significantly faster than those without HP treatment. And the multiple comparison results of multiple models showed that the difference between 3 times HP treatment and 1 to 2 times HP treatment was not statistically significant, and the average difference between 2 times HP treatment and single HP treatment was also not statistically significant. Conclusions:Hemoperfusion therapy can accelerate the recovery rate of ChE in AOPP patients; Whatever single HP treatment or multiple HP treatments, the recovery rate of ChE in AOPP patients has no significant difference.

OBJECTIVE:To improve the dispersion stability in water of Tussilago farfara powder,and to improve compliance of Xiao’er feike granules. METHODS:The effects of 4 kinds of dispersion stabilizer (sodium hexametaphosphate, dextrin, PEG4000 and lecithin) on dispersion stability of suspension in water were investigated during the grinding of T. farfara using rate of absorbance change(β)and Zeta potential as index;IR spectrum of samples were characterized. Using original formulation with-out dispersion stabilizer as control,the dispersion stability of new formulation granules in water were analyzed comparatively after adding dispersion stabilizer. RESULTS:Among 4 kinds of dispersion stabilizer,β of sample prepared by sodium hexametaphos-phate was the lowest,while Zeta potential of it was the highest;compared with original T. farfara,β of T. farfara grinded with 2.5% sodium hexametaphosphate decreased by 16.8%,and Zeta potential absolute value increased by 29.4%;no new peak was found in IR spectrum. Compared with control granules,granules suspension prepared by new formulation had lower β and higher Zeta potential absolute value (P<0.01);particle size was 30 μm and no large particle aggregation was found;β was less than 5.0% within 20 s sedimentation. CONCLUSIONS:During the preparation of Xiao’er feike granules,the application of sodium hexametaphosphate in the grinding of T. farfara powder can improve the dispersion stability of granules in water and the compliance of the preparation.

Objective To investigate the potential effect of glucagon-like peptide-1 (GLP-1) analogue exendin-4 (Ex-4) on immune function of T lymphocytes via neuroendocrine modulation mechanism in mice following severe burns.Methods Male BALB/C mice were randomly (ramdam number) divided into thermal injury group (n =50) and sham-thermal group (n =30).The thermal injury model was made by exposing the back skin of 15％ total body surface area (TBSA) to 95 ℃ water for 7 seconds,while in sham-thermal model the mice were immersed in 37 ℃ water instead.The expression of GLP-1 receptor (GLP-1 R) was determined in sorted CM + T cells from normal mice by immunofluorescence method.In ex vivo experiment,the mice were sacrificed at 24 h post-bum,then the mononuclear cells (MNC) from spleen were separated from both groups and cultured in RMPI 1640 with 10％ FCS (fetal calf serum) in presence of ConA (concanavalin A,5 μg/mL).Cells were pretreated with catecholamine receptor antagonist propranolol (prop) for 1 hour,followed by consecutive dose of Ex-4 for another 48 h.In in vivo experiment,prop (30 mg/kg) was i.p.injected 30 minutes before thermal injury,then Ex-4 (2.4 nmol/kg) was injected i.p.immediately after scalding.Mice were sacrificed at 6 h and 24 h after thermal injury,then the serum and the spleens were collected.Results GLP-1R was expressed on splenic CD4 + T cells from normal micc.Ex-4 exerted no marked effect on the functions of T cells in terms of proliferation and IL-2 secretion at all doses examined ex vivo,which was not affected by pretreatment with prop.In vivo,T cell functions were suppressed by Ex-4 in thermal mice (P ＜ 0.05),but was restored by pretreatment with prop.Regardless of ex vivo or in vivo,Ex-4 could induce T cells switched to Th2 response (P ＜ 0.05).Moreover,the Th2 switch by Ex-4 was greatly potentiated by prop intervention in thermal mice in vivo other than ex vivo.Norepinephrine level was increased and epinephrine was decreased by Ex-4 in thermal mice.Both norepinephrine and epinephrine levels were obviously enhanced by pretreatment with prop.Conclusions Ex-4 can inhibit the proliferation and IL-2 secretion of splenic T lymphocytes through the sympathetic nervous system,however,it might induce Th2 switch from Th cells by acting directly on GLP-1R.

Objective To detect the expression of interleukin (IL)-18 of the peripheral blood cells and IL-18 receptor α chain(IL-18Rα) on the surface of CD_3~+ cells in patients newly diagnosed as immune thrombocytopenia (ITP) before medication and to explore the roles of IL-18 and IL-18Rα in the development of ITP. Methods Eighteen out-patients or inpatients with acute ITP accepting treatment in Qilu Hospital were enrolled in this study and 15 matching healthy subjects were taken as control. Plasma IL-18 level was detected with enzyme linked immunosorbent assay (ELISA), the expression of IL-18Rα on CD_3~+ lymphocytes and total lymphoeytes were measured with flow cytometry; T-bet and GATA-3 mRNA were measured with reverse transcriptase polymcrase chain reaction (RT-PCR). Results The expression of IL-18 in acute ITP plasma was (468. 57 ± 141.62) ng/L and IL-18Rα on the surface of CD_3~+ cells and lymphocytes were (8.50 ±3. 16)% and (9. 16±2.98)% respectively. The levels of IL-18 and IL-18Rα were increased in active ITP patients as compared with those in the controls (P <0. 05). The levels of IL-18 mRNA (0. 12 ±0. 02) and T-bet mRNA (0. 07 ±0. 02) were significantly increased in patients with active ITP as compared with those in the controls (P <0.05), while GATA-3 mRNA (0.0039±0.0014) were significantly decreased in patients with active ITP (P < 0. 05). The balance between T-bet and GATA-3 was significantly disturbed in ITP. Conclusions Through the variation of the levels of gene and protein, our study showed that IL-18 and IL-18Rα might upregulate the expression of Th1-cytokines in ITP patients. It is also suggested that IL-18 has potential association with the development of ITP. Especially, it may provide a new treatment method for ITP by regulating the ratio of T-bet and GATA-3 and resuming the balance of Th1/ Th2.

Objective To investigate the association between the HLA-DRB1 gene polymorphisms and susceptibility of pulmonary tuberculosis (TB) in patients with type 2 diabetes mellitus in North China. Methods A 1∶1 matched case-control study was adopted. Polymerase chain reaction-sequence-specific primers techniques (PCR-SSP) and restriction fragment length polymorphism (RFLP) was used to type polymorphisms (DR15, DR16, DR1, DR11). Information on environmental-related risk factors and pathological changes of tuberculosis was collected using a pre-tested standard questionnaire. Variance analysis, Chi-square, univariate and multivariate conditional Logistic analysis were conducted with SPSS 12.0 for Window. Results A sample of 124 pairs of cases and controls was studied. Univariate analysis demonstrated that DR15 mutant increased the risk of susceptibility of pulmonary tuberculosis (OR＝2.461, 95%CI: 1.363~4.444, P=0.002),and it would further increased if DR16 mutant occurred together (OR=4.904, 95%CI: 1.554~15.476). In multivariate analysis, DR15 mutant also associated with susceptibility of pulmonary tuberculosis (OR=2.996, 95%CI: 1.51~5.945). Conclusion Polymorphism of DR15 genotype might be a susceptible genotype of TB patients with type 2 diabetes mellitus in North China.

JadH is a bifunctional hydoxylase/dehydrase involved in jadomycin biosynthesis; it catalyzes a post-PKS modification reaction to convert 2,3-dehydro-UWM6 to dehydrorabelomycin. To identify the key residues involved in substrate-binding and catalysis, structural modeling and multiple sequence alignments of JadH homologs were performed to predict nine residues at the proximity of substrate. Site-directed mutagenesis of the corresponding residues and in vitro evaluation of the activities of the mutant enzymes, indicate these mutations severely reduced JadH activity. Our results indicate these residues are specifically involved in substrate-binding or catalysis in JadH.
Amino Acid Sequence ; Catalysis ; Hydro-Lyases ; genetics ; metabolism ; Isoquinolines ; metabolism ; Mixed Function Oxygenases ; genetics ; metabolism ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Mutant Proteins ; metabolism ; Naphthoquinones ; metabolism ; Streptomyces ; metabolism ; Substrate Specificity

Two component system is a signal transduction system. It typically consists of a sensor histitine kinase and a cognate response regulator (RR) component. The activity of RR is regulated by a phosphorylation dependent mechanism. In recent years, the existence of atypical response regulators (ARRs), which rely on a phosphorylation independent mechanism to regulate their activity, have been recognized. ARRs are involved in the regulation of bacterial growth and development, antibiotic biosynthesis, iron transport, among others. Here we review the recent advances in the understanding of the structure and function of atypical response regulators, by using JadR1, a regulator in jadomycin biosynthesis in Streptomyces, as an example to elucidate the novel mechanism used by ARR to fine-tune its activity.
Bacterial Proteins ; genetics ; Gene Expression Regulation, Bacterial ; Gene Expression Regulation, Developmental ; Genes, Regulator ; genetics ; Histidine Kinase ; Isoquinolines ; metabolism ; Naphthoquinones ; metabolism ; Phosphorylation ; Protein Kinases ; genetics ; RNA-Binding Proteins ; genetics ; Signal Transduction ; Streptomyces ; metabolism ; Transcription Factors ; genetics