Objective To investigate the effects of clinical pharmacist intervention in the clinical application of antibiotics combined with the index management.Methods The data of antibiotics usage rate and intensity, the microbial test sample submission rate, and the clean incision preventive usage rate of inpatients and outpatients were analyzed by chi-square test in the same period before (2015) and after (2016) the clinical pharmacist intervention.Results After intervention, the antibiotics usage rate of inpatients and outpatients were lower than that of 2015 (50.02% and 25.72%, P<0.05).In 2016, the usage intensity of antibiotics was 50.59%, while it was 62.39% in 2015.At the same time, the microbial test sample submission rate increased from 13.96% to 27.49%(P<0.05).In 2016, the clean operation preventive usage rate of antibiotics decreased month by month.In the meantime, the reasonable rate of delivery timing, variety selection, and administration time of clean operation preventive usage of antibiotics were on the rise.Conclusions The professional intervention of clinical pharmacistis benefit for the routine, standardization, and professionalization of clinical antibiotics application.It also promotes the rational use of drugs and the progress of hospital pharmacy.

Chaetominine is a quinazoline alkaloid originating from the endophytic fungus Aspergillus fumigatus CY018. In this study, we showed evidence that chaetominine has cytotoxic and apoptotic effects on human leukemia K562 cells and investigated the pathway involved in chaetominine-induced apoptosis in detail. Chaetominine inhibited K562 cell growth, with an IC50 value of 35 nM, but showed little inhibitory effect on the growth of human peripheral blood mononuclear cells. The high apoptosis rates, morphological apoptotic features, and DNA fragmentation caused by chaetominine indicated that the cytotoxicity was partially caused by its pro-apoptotic effect. Under chaetominine treatment, the Bax/Bcl-2 ratio was upregulated (from 0.3 to 8), which was followed by a decrease in mitochondrial membrane potential, release of cytochrome c from mitochondria into the cytosol, and stimulation of Apaf-1. Furthermore, activation of caspase-9 and caspase-3, which are the main executers of the apoptotic process, was observed. These results demonstrated that chaetominine induced cell apoptosis via the mitochondrial pathway. Chaetominine inhibited K562 cell growth and induced apoptotic cell death through the intrinsic pathway, which suggests that chaetominine might be a promising therapeutic for leukemia.
Apoptosis ; Aspergillus fumigatus ; Caspase 3 ; Caspase 9 ; Cell Death ; Cell Line* ; Cytochromes c ; Cytosol ; DNA Fragmentation ; Fungi ; Humans* ; Inhibitory Concentration 50 ; K562 Cells ; Leukemia* ; Membrane Potential, Mitochondrial ; Mitochondria

Objectives To investigate the effects of cell aging on the disorders relating to gastric mucosa aging.Methods A treatment of 200 μmol/L H2O2 was used to induce senescence of human gastric epithelial cell line GES-1,and the cell growth curve was monitored.Senescence secretory phenotypes were observed by detecting the protein level of p53 and p16INK4a with senescence-associated β-galactosidase(SA-β gal)staining and Western blot testing.The mRNA levels of senescence-associated secretory phenotype(SASP)factors in human gastric epithelial GES-1 cell including IL-1β,IL-6,IL-8,TGF-β、IFN-γ,and VEGF-A were detected by RT PCR.The mRNA expression levels of IL-1β,IL-6,IL-8,TGF-β,IFN-γ,and VEGF in the conditioned medium were detected by ELISA analysis.Results The 200 μmol/L H2O2-induced GES-1 cells stopped proliferating after 3 days of treatment,and cells enlarged and flattened at 10 days.The increased SA-β-gal staining(P＜0.001) and the increased expression levels of p53 and p16INK4a proteins indicated the success of establishing the aging model of GES-1.The mRNA levels of IL 1β,IL6,IL8,TGF-β,and IFNγ were higher(t=2.94,3.38,3.15,3.64,2.97;P=0.015,0.000,0.000,0.000,0.000)and the mRNA level of VEGF-A was lower(t=2.31,P =0.20) in senescent GES-1 cells than in the control group.In the conditioned medium of senescent GES-1 cells,the levels of IL-1β,IL6,IL8,TGF-β1,and IFNγ were higher in the H2O2-induced group [(3.12±0.21)μg/L,(4.26±0.15)μg/L,(3.37±0.14)μg/L,(5.34±0.19)μg/L,and(2.90±0.47)μg/L]than in the negative control group[(0.24±0.04,0.04±0.07,0.52±0.02,1.05±0.10,0.52±0.02,respectively,P＜0.001)],while the level of VEGF was lower in the H2O2-induced group than in the negative control group(0.21±0.03)μg/L vs (0.59±0.07)μg/L(P＜0.05).Conclusions The changes in senescence-associated secretory phenotype factors of the aging human gastric epithelial cells induced by oxidative stress may promote chronic gastritis and gastric cancer.

Objective:To analyze the effects of the main drug resistance mutations in the integrase (IN) region on the resistance of HIV-1 CRF01_AE strains, and compare the differences with subtype B strains.Methods:Seven IN region mutations or combined mutations (T66K, F121Y, Q148K, N155H, G118R, R263K, Q148K/N155H) were selected from the HIV drug resistance database of Stanford University in the United States, and introduced to the IN region of HIV-1 B subtype infectious clone pNL4-3 and CRF01_AE infectious clone pGX002 by seamless cloning, homologous recombination and point mutation. The mutant plasmids were transfected into 293T cells for virus packaging. The culture was expanded in MT2 cells and infectious titers were detected. Half maximal inhibitory concentrations (IC 50) of four integrase inhibitors (INSTIs), raltegravir (RAL), elvitegravir (EVG), dolutegravir (DTG) and bictegravir (BIC), against 14 mutant viruses were detected and compared with the IC 50 against the wild-type viruses. Results:B subtype and CRF01_AE plasmids carrying seven IN region mutations or combined mutations were successfully constructed, and 14 recombinant viruses were packaged with an infectious titer of 10 4-10 6 median tissue culture infective dose (TCID 50)/ml. The recombinant viruses replicated efficiently in MT2 cells. The concentrations of HIV-1 p24 antigen contained in the supernatants of cell culture reached 830-2 700 ng/ml. Five mutations or combined mutations (T66K, F121Y, Q148K, N155H, Q148K/N155H) caused CRF01_AE and B subtype strains to be highly resistant to RAL and EVG, resulting in an increase in the IC 50 by 200 times and 2 000 times or more as compared with the IC 50 against the wild-type viruses. The same mutation-caused fold changes of IC 50 of RAL and EVG against CRF01_AE were significantly lower than that of subtype B ( P<0.01). Q148K/N155H mutation caused B subtype and CRF01_AE to be highly resistant to DTG and BIC, with IC 50 increased by more than 50 times. Other mutations had little effects on the sensitivity to DTG and BIC. Conclusions:Fourteen HIV-1 strains carrying seven INSTI resistance mutations based on B subtype and CRF01_AE were constructed. Five mutations resulted in high resistance to RAL and EVG, and there was a high level of cross-resistance. Resistance to RAL and EVG caused by the same mutation was higher in B subtype than in CRF01_AE. The combined mutation of Q148K and N155H was associated with greater resistance to DTG and BIC, indicating that the genetic barrier of DTG and BIC resistance was high. DTG and BIC could effectively inhibit the strains carrying INSTI resistance mutations without obvious subtype difference.