Cost-utility analysis of azacitidine versus decitabine in the treatment of myelodysplastic syndrome / 药物流行病学杂志

Objective To evaluate the economics of azacitidine versus decitabine in the treatment of myelodysplastic syndrome(MDS)from the perspective of health system in China,and provide references for clinical drug selection.Methods A Markov model was constructed based on the data of a multi-center retrospective cohort study(NCT01409070),with a model simulation time limit of 10 years and the cycle period of 28 days.The quality-adjusted life years(QALYs)was used as health output index and incremental cost-utility ratio(ICUR)was calculated to evaluate the economics of azacitidine versus decitabine in the treatment of MDS.One-way sensitivity analysis and probabilistic sensitivity analysis were adopted to examine the robustness of the model simulation results.Results The results of basic analysis showed that compared with decitabine group,the total cost of azacitidine group reduced by 281 185.46 yuan and the utility increased by 0.17 QALYs.Azacitidine therapeutic regimen was the absolute dominance plan.One-way sensitivity analysis showed that progression-free survival state utility value,discount rate and decitabine cost had greater influence on the results.The results of probabilistic sensitivity analysis suggested that azacinidine therapy was always economical within the willingness to pay threshold range of 3 times Chinese per capita gross domestic product in 2021.Conclusion From the perspective of health system in China,azacitidine has more cost-utility advantages than decitabine in the treatment of MDS.

Expression of high-mobility group B1 released by exosome in nonalcoholic fatty liver disorder and regulated by TLR4 signal / 解放军医学杂志

Objective To investigate the release of enterogenic and hepatogenic high mobility group protein B1(HMGB1)through exosomes and its regulatory pathway.Methods We used wild-type(WT)and ASC-/-mice for this study.We randomly selected five mice per group from each strain and fed them either a normal diet(ND)or a high-fat diet(HFD)for eight weeks.The control group consisted of WT mice fed with the normal diet;the HFD group were WT mice with the HFD;the microflora disturbance(MD)group were ASC-/-mice fed with the normal diet;the high-lipid microflora disturbance(HLMD)group were ASC-/-mice with HFD.We used confocal microscopy to detect the co-localization of liver and intestinal exosome markers with HMGB1.We then measured the expression level of HMGB1 content in exosomes by Western blotting and PCR.The AML12 cells were treated with palmitic acid(PA)and lipopolysaccharide(LPS)for 24 h to build an in vitro model.We also detected HMGB1/CD63 levels using Western blotting.To understand the regulatory mechanism of exosome release,we employed siRNA intervention.Results The secretion of exosomes increased significantly in HFD group compared with control group[(3.5±0.2)ng/ml vs.(1.1±0.3)ng/ml,P<0.05],HLMD group compared with those in MD group[(3.2±0.2)ng/ml vs.(1.9±0.4)ng/ml,P<0.05].Using immunofluorescence detection,we observed increased co-localization of exosome markers(ALP or VPS16)with HMGB1 in HFD group compared with control group.We also observed this in AML12 cells treated with PA and LPS compared with blank control.The PCR data showed that HMGB1 in hepatocyte exosomes was higher in HFD group compared with control group(41.5±10.2 vs.1.3±0.3,P<0.05),HLMD group was significantly higher than that in MD group(48.6±7.2 vs.1.5±0.5,P<0.05).TLR4 expression was higher in HFD group compared with control group(13.8±6.2 vs.2.8±0.9,P<0.05),HLMD group compared with MD group(22.6±4.1 vs.2.5±1.5,P<0.05).In intestinal mucosal cells,the co-location of HMGB1 and exosome marker CD63 was significantly higher in HFD group compared with control group(0.6±0.2 vs.0.4±0.1,P<0.05),and HLMD group compared with MD group(0.9±0.2 vs.0.5±0.1,P<0.05).In vitro,the HMGB1 of exosomes was increased in endotoxin group(5.1±0.8)and high lipid endotoxin group(5.5±0.7)compared with control group(3.8±0.6,P<0.05).On the other hand,the HMGB1 of exosomes in the cell siRNA intervention group was not increased compared with control group(3.7±0.6 vs.3.8±0.6,P>0.05).Conclusion HMGB1 is released by exosomes in hepatocytes and intestinal cells,and regulated by Toll-like receptor 4(TLR4)under a high-fat diet and intestinal flora disorder,which may be one of the contributing factors in promoting the development of steatohepatitis.

Correlation between physical fitness and frequency of breakfast consumption of middle school students / 中国学校卫生

Objective@#To investigate the breakfast consumption of middle school students and to analyze its relationship with physical fitness, so as to provide reference for improving physical fitness of middle school students.@*Methods@#A total of 2 732 middle school students from Shangrao City were selected in September 2021 by random cluster stratified sampling. The breakfast consumption behaviors of middle school students were investigated by questionnaire, and the general information, family information and other lifestyle behaviors were collected. The physical fitness test includes grip strength, standing long jump, 1 minute sit up, sit forward bend, 50 m run and 20 m shuttle run test (20 m SRT) to evaluate the strength, flexibility, speed and endurance of middle school students. χ 2 tests were used to compare the correlation between different demographic characteristics, breakfast behavior and physical fitness,and Logistic regression analysis was used to infer the correlation strength between breakfast behavior and physical fitness.@*Results@#The detection rate of physical fitness failure among middle school students was 21.5%. There were statistically significant differences between breakfast frequency and grip strength and 20 m SRT( χ 2=8.27, 13.90, P < 0.05 ). Logistic regression analysis results showed that 20 m SRT was positively correlated with breakfast frequency (sometimes eat breakfast, OR =1.51, skip or occasionally eat breakfast OR =2.08, P <0.05).@*Conclusion@#The low frequency of breakfast consumption of middle school students is associated with low performance on 20 m SRT. Schools and families should pay attention to the breakfast consumption of middle school students to ensure adequate daily nutrition intake.

Effect of different anesthesia methods on erythrocyte immune function in mice

OBJECTIVE@#To explore effect of different anesthesia methods and different anesthetics on erythrocyte immune function in mice.@*METHODS@#The mice were anesthetized by isoflurane and ether inhalation, and also under intraperitoneal anesthesia with sodium pentobarbital and chloral hydrate. Blood was collected from the ventro-cardinal vein. Automatic blood cell analyzer was used for routine blood examination, and the canthine oxidase method was used to measure the superoxide dismutase (SOD) activity. Lipid peroxidation product malondialdehyde (MDA) was measured with TBA, and glutathione peroxidase (GSH-Px) was measured with DTNB, and then the effect of different anesthesia methods and different anesthetics on erythrocyte immune function in mice was observed.@*RESULTS@#Hct level of chloral hydrate intraperitoneal injection group was significantly higher than the other three groups (P<0.05). And the MDA levels in the pentobarbital sodium group were significantly higher than the other three groups (P<0.05). SOD and GSH-Px of the chloral hydrate and sodium pentobarbital intraperitoneal injection group were significantly lower than the other two groups; RBC-C 3bRR and RBC-ICR of the chloral hydrate and sodium pentobarbital intraperitoneal injection group were significantly lower than the other two groups.@*CONCLUSIONS@#Different drugs can induce changes in immune function of mice at different levels. Isoflurane and ether have less damage to animal body, while chloral hydrate and sodium pentobarbital intraperitoneal injection have a certain inhibitory effect on the animal body respiratory system and can cause greater damage to the body. Therefore, the reasonable selection and control of anesthetics are very important in order to avoid the experimental errors caused by anesthesia.

Construction of biofilm formation related mutants in Vibrio parahaemolyticus / 中华预防医学杂志

<p><b>OBJECTIVE</b>To construct the mutants of biofilm related genes in Vibrio parahaemolyticus and confirm the mutants.</p><p><b>METHODS</b>The homologous upstream and downstream flanking fragments of target gene were amplified by using PCR, and the fusion homologous fragment was amplified by using the two flanking fragments as template. Then the fusion homologous fragment was digested by restriction enzyme and cloned into suicide plasmid pDS132. The recombinant plasmid was transferred into Vibrio parahaemolyticus RIMD 2210633 through conjugation. The mutants were screened and identified by PCR and the phenotype of one mutant was analyzed in order to verify that the mutants were constructed successfully.</p><p><b>RESULTS</b>Six recombinant plasmids carrying the fusion homologous fragments of genes vbfR, crp, hns, swrZ, swrT and cpsR respectively were constructed and identified by PCR. The amplification products of 1190, 1128, 1136, 953, 1242 and 1112 bp were obtained respectively. The six mutants (ΔvbfR, Δcrp, Δhns, ΔswrZ, ΔswrT and ΔcpsR) were constructed using recombinant plasmids. Verified by PCR, the size of amplification products of mutants (1190, 1128, 1136, 953, 1242 and 1112 bp respectively) was less (610, 739, 421, 542, 427 and 1367 bp respectively) than the corresponding positive control. Meanwhile, none of the products was amplified using the primers locating on the target gene. One mutant Δhns was selected to test the ability of biofilm formation. The result showed that the ability of biofilm formation of mutant Δhns was increased compared with the wild type.</p><p><b>CONCLUSION</b>Six mutants of biofilm related genes in Vibrio parahaemolyticus were constructed and tested by molecular and phenotype experiment to confirm that the mutants were constructed successfully.</p>