Objective: To observe the effect of imatinib mesylate on pulmonary fibrosis (PF) induced by bleomycin in mice and to explore the related mechanism. Methods: Totally 120 C57BL/6 mice were evenly randomized into control group, model group, dexamethasone group and imatinib group. The pulmonary fibrosis model was established using a single intratracheal infusion of bleomycin; the corresponding drugs were given to mice in each group. Ten mice was sacrificed in each group on day 7, 14, and 21 after operation, respectively. The expression of matrix metalloproteinase 1 (MMP-1), tissue inhibitor of metalloproteinase 1 (TIMP-1), and transforming growth factor β1(TGF-β1) in the lung tissues was semi-quantitatively analyzed by immunohistochemistry method. Results: Immunohistochemistry results showed that the expression of TIMP-1, MMP-1, and TGF-β1 in lung tissues of the dexamethasone group and imatinib group was significantly lower than that in the model group(P<0.01). There was a positive correlation between TGF-β1 and TIMP-1 expression(r=0.243, P=0.004). A negative correlation was found between MMP-1 and TIMP-1 in all the other 3 groups other than in the normal control group(r= -0.291, P<0.0001). Conclusion: Imatinib may downregulate TGF-β1 expression, inhibit TIMP-1 expression, and upregulate MMP-1 expression, maintaining the balance of TIMP-1/MMP-1, subsequently inhibit the development of pulmonary fibrosis, showing a similar effect of dexamethasone.

OBJECTIVE: To obtain data related to status quo of clinical pharmacy service provision of tertiary hospitals, find problems in clinical pharmacy service provision, based on which provide advice on policy formulation. METHODS: A face-to-face interview survey was conducted to collect data on status quo of clinical pharmacy service provision of Tertiary hospitals which were analyzed with descriptive statistics tools. RESULTS: The proportions of clinical pharmacy related workload to 86.4% of the clinical pharmacists are larger than 40%; relatively more clinical pharmacists focus their work on prescription checking(25.9%), therapeutic regimen(17.3%) or pharmaceutical ward round(15.7%) than other services; medical documentation(53.6%), group consultation(51.7%) and drug abuse prevention(27.3%) are less performed by clinical pharmacists than other duties; 96.9% of the physicians recognized the clinical value of clinical pharmacists' work, and 97.1% of the physicians adopted the clinical pharmacist's advices; medical history checking, medication guidance, medication counseling and pharmaceutical ward round are with relatively high coverage(75.3%, 78.0%, 76.2%, and 73.5%) and satisfaction(77.8%, 81.3%, 79.2%, and 76.1%) among the patients. CONCLUSION: The construction of clinical pharmacy service system in tertiary hospitals in our country is beginning to obtain achievement.

【Objective】 To establish a stable human megakaryocytic cell line with low expression of Le^y antigen to further study the role of Le^y on activation of platelets. 【Methods】 The expression level of the Le^y antigen in a human megakaryocytic cell line, DAMI, was determined using Western Blot and flow cytometry. The expression level of genes that encode fucosyltransferase (FUTs), which was involved in the biosynthesis of Le^y antigen, was also determined to identify the candidate genes to be knocked out. The candidate FUT gene was knocked out via a CRISPR/Cas 9 gene knockout system and cells with low Le^y antigen expression were sorted by flow cytometry. The sorted cell line was cultured and characterized. 【Results】 The Le^y was expressed intensively on DAMI cell. FUT1 and FUT4 mRNA was expressed relatively higher, both may be key enzymes for the biosynthesis of the Le^y antigen. In the DAMI cell line with the knockout of FUT1 gene, the expression of the Le^y adntigen was remarkedly reduced, while cell proliferation was not affected compared to the wildtype control cells. 【Conclusions】 Since various FUTs contributes to the biosynthesis of the Le^y antigen, the knockout of the primary one of them cannot totally block its biosynthesis, but only reduce its expression. In this study, a stable FUT gene knockout human megakaryocyticcell line is established using CRISPR/Cas 9 technology, which provides basis for the study of the impact of the Le^y antigen on platelet functions.

【Objective】 To analyze the influence of β-lactam antibiotics on RBC aging and clearance by detecting various indicators of aging and clearance on RBCs, as well as the differences in phagocytosis for erythrocytes before and after drugs treated in vitro. 【Methods】 RBCs were treated by β-lactam antibiotics, including Penicillin, Cefepime, Cefoperazone and Ceftazidime, and the changing of phosphatidylserine (PS) and clearance related CD markers, including CD35, CD47, CD55 and CD59 on the surface of the RBCs, were detected by flow cytometry at 0h and 24h after drugs treatment. The proportion of acanthocytes by microscope also at 0h and 24h after drugs treatment was calculated. The phagocytosis of drug-treated RBC was detected by monocyte monolayer assay (MMA). Untreated RBCs were incubated in PBS by the same condition as a negative control.The influence of β-lactam antibiotics on RBC aging and clearance by all the results above was studied. 【Results】 Compare to the untreated RBCs, the drug treated RBCs showed a higher PS level on the cell surface. The results showed by percentage as following(0 h vs 24 h): Penicillin 9.42% vs 93.30%, Cefepime 3.88% vs 57.27%, Cefoperazone 4.71% vs 75.75% and Ceftazidime 3.05% vs 43.19%. The acanthocytes ratio was as following(0 h vs 24 h): Penicillin 7.33% vs 86%, Cefepime 2.67% vs 52.67%, Cefoperazone 3.33% vs 67.67% and Ceftazidime 3.33% vs 90.67%. On the opposite, the clearance related CD markers, showed an obviously lower level after drugs treated(0 h vs 24 h): CD35: Penicillin 7.36% vs 11.87%, Cefepime 0.14% vs 28.51%, Cefoperazone 11.85% vs 21.55% and Ceftazidime 7.63% vs 8.73%; CD47: Penicillin 1.22% vs 9.13%, Cefepime 1.80% vs 0.86%, Cefoperazone 0.08% vs 6.85% and Ceftazidime 1.54% vs 5.50%; CD55: Penicillin 14.46% vs 44.31%, Cefepime 17.27% vs 38.41%, Cefoperazone 19.28% vs 33.28% and Ceftazidime 14.62% vs 34.13%; CD59: Penicillin 4.71% vs 20.56%, Cefepime 4.03% vs 7.60%, Cefoperazone 5.91% vs 22.38% and Ceftazidime 5.93% vs 30.89%. Drug-treated RBCs attached more to monocytes than untreated RBCs. 【Conclusion】 The β-lactam antibiotics could induce the changing of PS and the clearance of related CD markers on surface of RBCs. They also could lead acanthocytes and make the RBCs more susceptible to phagocytosis by monocytes. The β-lactam antibiotics could promote the RBCs aging and clearance, which might deteriorate the DIIHA.

In MRI examination, RF heating of implants will affect the safety of implant wearers. The conductivity of various tissues in the human body is significantly different, and the medium conductivity will affect the distribution of the RF electric field. Therefore, it is necessary to study the RF heating of different medium conductivity. Based on the analysis of the principle of MRI RF heating, this study build the model of the bird cage coil, ASTM standard phantom and lead, and the conductivity of several typical human tissues is selected as the conductivity in the experiment. Then calculate the power deposition of the lead at 64 MHz. The results show that the medium conductivity has no effect on the distribution of electric field and power deposition, and the hot spot distribution remains unchanged under different conductivity; The smaller the conductivity is, the larger the power deposition of the lead is, and the greater the temperature rise of the lead caused by RF heating is; The change of conductivity and power deposition is approximately linear. At the limit of 2 W/kg whole body specific absorption rate(SAR), the conductivity decreases, and the wire power deposition increases sharply.

Therapeutic antibody drugs have achieved great success in clinical practice. However, their efficacy and safety still need to be improved. At the same time, excessive concentration of drug targets will cause problems such as repeated development and waste of resources. Therefore, pharmaceutical companies need to explore differentiated discovery strategies when researching antibody drugs in order to survive and develop in the fierce market competition. In this paper, the differential development strategy of therapeutic antibody drugs is discussed from the aspects of drug sources and formats, drug target selection, drug mechanism and differential drug characteristics.
Drug Delivery Systems ; Pharmaceutical Preparations

To establish a method for identifying protein epitopes recognized by therapeutic monoclonal antibodies, the programmed death receptor-1 (PD-1) was selected as the target protein. Based on the alanine scanning strategy, a rapid expression method of antigen mutants combining site-directed mutagenesis with mammalian cell expression system was established, the conditions for eukaryotic expression element amplification and cell transfection expression were established. 150 PD-1 protein mutants were co-expressed, and the binding ability of these mutants to anti-PD-1 antibody Pembrolizumab was identified. The epitopes of Pembrolizumab were determined based on the binding ability of protein mutants to antibodies and combined with protein structure analysis, which was highly consistent with the reported crystal structure-based epitopes, indicating that this method is simple and accurate and can be used for epitope mapping of therapeutic monoclonal antibodies.
Animals ; Antibodies, Monoclonal ; Antigens ; Epitope Mapping ; Epitopes/genetics*

Driven by the development of medical technology and the increasing workload of hospitals, high-cost medical consumables are playing an ever more important role. Operating theatres, as the biggest consumer of high-cost consumables, cannot afford to manage the consumables in a detailed manner under the traditional approaches of management. This article elaborates on the complete management of the high-cost consumables with the help of bar code technology. Information management of high-cost consumables has brought about higher work efficiency, streamlined management process, greater medical safety and higher economic viability of hospitals.
Costs and Cost Analysis ; Electronic Data Processing ; Equipment and Supplies, Hospital ; economics ; Operating Rooms

OBJECTIVEMaple syrup urine disease (MSUD) is an autosomal recessive metabolic disorder that is caused by mutations in the subunits of the branched chain α-ketoacid dehydrogenase (BCKD) complex. This report presents a Han ethnic Chinese newborn infant with the severe classic form of MSUD caused by two novel missense mutations in the BCKDHB gene.

METHODThe clinical and biochemical data of a Chinese neonate with classic form of MSUD were analyzed, and the DNA sequences of BCKDHA, BCKDHB, DBT and DLD genes were investigated for mutations. Then the DNA samples of the proband and the patient's parents were tested with Sanger sequencing.

RESULTThe manifestations of this patient were poor feeding, low reaction, and compensatory metabolic acidosis. Tandem mass spectrometry (MS/MS) showed that leucine and valine were significantly higher than normal. Urine gas chromatography-mass spectrometry (GC/MS) showed significant abnormality. Brain CT scan showed white matter changes. We identified two previously unreported mutations in the BCKDHB gene, p.Leu194Phe (c.580 C>T) and p.Ser199Arg (c.597 T>G) in exon 5. Segregation analysis showed that the novel mutation p.Ser199Arg was maternally inherited and the novel mutation p.Leu194Phe was paternally inherited. Neither mutation was found in the 186 alleles of 93 normal Han ethnic Chinese individuals. In human BCKDHB protein crystal structure, the 194th and 199th amino acids changes are likely to affect the spatial structure of the protein. The 194th and 199th amino acid of human BCKDHB protein was conserved among species. PolyPhen protein function prediction indicated that the 194th and 199th amino acid changes were likely to affect protein function.

CONCLUSIONTwo novel missense mutations were identified in the BCKDHB gene in the Chinese patient with MSUD.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide) ; genetics ; Alleles ; Asian Continental Ancestry Group ; Base Sequence ; DNA ; Exons ; Gas Chromatography-Mass Spectrometry ; Humans ; Infant ; Infant, Newborn ; Maple Syrup Urine Disease ; genetics ; Mutation, Missense ; Tandem Mass Spectrometry

Objective:To explore the targets and relevant signaling pathways of Suoquanwan in the treatment of enuresis using network pharmacology，and animal expriments are applied to further define its mechanism of action. Method:Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP） database was used to screen out active chemical components of Suoquanwan，varieties of systematic biological databases were integrated to construct the "active component-disease-target" network relationship，and the common protein protein interaction network（PPI） network genes were functionally enriched. Quantitative real time polymerase chain reaction（Real-time PCR） and Western blot were used to verify the effect of Suoquanwan on AVPR2 and DRD2 gene. Result:A total of 32 active ingredients were screened from Suoquanwan. These active ingredients were interacted with 131 potential targets relating to Enuresis，which contained 14 core target genes，namely arginine vasopressin receptor 2 （AVPR2）， neurotrophic receptor tyrosine kinase 1（NTRK1）， dopamine receptor D2（DRD2）， opioid receptor mu 1（OPRM1）， 5-hydroxytryptamine receptor 1A（HTR1A）， 5-hydroxytryptamine receptor 1B（HTR1B），solute carrier family 6 member 4（SLC6A4），Adrenoceptor Alpha 2A（ADRA2A）， prostaglandin-endoperoxide synthase 2（PTGS2）， cholinergic receptor muscarinic 2（CHRM2）， solute carrier family 6 member 3 （SLC6A3）， 5-hydroxytryptamine receptor 6（HTR6）， solute carrier family 6 member 2（SLC6A2）， cytochrome P450 family 2 subfamily C member 19（CYP2C19）. Gene enrichments mainly involved to G protein-coupled receptor signaling pathway，regulation of trans-synaptic signaling，regulation of neurotransmitter transport and neuroactive ligand-receptor interaction. Real-time PCR and Western blot results showed that Suoquanwan could enhance the expression of AVPR2 in rat kidney，and weaken the expression of DRD2 in rat adrenal. Conclusion:The main chemical constituents in Suoquanwan may alleviate enuresis by regulating AVPR2 and DRD2 and then participating in the G protein-coupled receptor signaling pathway，regulation of trans-synaptic signaling，regulation of neurotransmitter transport and other biological processes.