Adult ; Aged ; Bronchoalveolar Lavage Fluid ; chemistry ; cytology ; Chemokine CCL3 ; metabolism ; Humans ; Macrophage Migration-Inhibitory Factors ; metabolism ; Macrophages ; metabolism ; pathology ; Male ; Middle Aged ; Silicosis ; metabolism ; pathology

OBJECTIVE:To establish a method for the determination of dasatinib concentration in human plasma and study the bioequivalence of 2 kinds of tablets. METHODS:In a randomized two-way crossover study,24 healthy male volunteers were divid-ed into two groups,and were administered respectively with test and reference preparations 100 mg under fasting and fed condi-tions. The plasma concentration of dasatinib was determined by LC-MS/MS. Using imatinib mesylate as internal standard,the deter-mination was performed on Welchrom C18 column with mobile phase consisted of acetonitrile-0.1% formic acid(70∶30,V/V). Posi-tive ion scanning was conducted under MRM mode,ESI,and ion pair for quantitative analysis were m/z 488.5→401.2 (dasatinib) and m/z 494.6→394.2(internal standard). DAS 3.2.8 software was used for data processing and variance analysis was adopted to in-vestigate the bioequivalence of 2 kinds of tablets. RESULTS:The linear rang of dasatinib was 1-300 ng/ml. The pharmacokinetic pa-rameters of test and reference preparations under fasting conditions were as follows:cmax were (165.599 ± 67.592) and (164.533 ± 77.960)ng/ml;tmax were(1.145±0.504)and(1.080±0.467)h;t1/2 were(5.080±2.262)and(3.771±1.596)h;AUC0-36 h were (550.487 ± 256.494) and (585.986 ± 324.885) ng·h/ml. The pharmacokinetic parameters of test and reference preparations under fed conditions were as follows:cmax were(163.058±47.533)and(165.440±53.012)ng/ml;tmax were(1.630±1.066)and(1.576± 0.530)h;t1/2 were(4.720±2.677)and(4.311±2.610)h;AUC0-36 h were(568.036±192.521)and(601.100±216.855)ng·h/ml. Relative bioavailability of AUC0-36 h under fasting and fed conditions were(100.2±7.5)% and(99.2±3.8)%. Analysis of variance showed there were no significant difference in the pharmacokinetic parameters of between 2 preparations and cyde(P>0.05),there was statistical significance among subjects(P<0.05). CONCLUSIONS:LC-MS/MS method can determine the concentration of da-satinib in human plasma rapidly;and the two preparations are bioequivalent.

Background:Clinical features and outcomes of heart failure (HF) with mid-range ejection fraction (HFmrEF) remain controversial.Thus,we systematically reviewed literatures of clinical research to assess and analyze characteristics and prognosis of patients with HFmrEF.Methods:PubMed,Embase,and Web of Science were searched for cohort studies up to April 23,2019.Clinical features and multivariate adjusted hazard ratios (HRs) of endpoints of short-term all-cause mortality (SAM),long-term all-cause mortality (LAM),long-term cardiovascular death (LCD) and long-term HF rehospitalization (LHR) among patients with HFmrEF and HF with preserved ejection fraction (HFpEF),HF with reduced ejection fraction (HFrEF) were well addressed.The primary outcome was LAM.Results:Totally 19 studies were included in this study with 164,678 patients enrolled.The follow-up time of LAM was 3.6 ± 2.5 years.HRs of LAM,SAM,LCD,LHR indicated that the risks of patients with HFmrEF were higher than HFpEF patients but lower than HFrEF patients,as for LAM,HFmrEF:HFpEF (reference) HR:1.07,95％ confidence interval (CI):1.00-1.15 (I2=63％,P =0.0005);HFmrEF:HFrEF (reference) HR:0.80,95％ CI:0.73-0.88 (I2=70％,P ＜ 0.0001).However,HFmrEF patients had the lowest rate in LAM (30.94％),SAM (2.73％),LCD (17.45％),LHR (26.36％) compared with the other two groups.Conclusions:This systematic review and meta-analysis compared features and prognosis between patients with HFmrEF and HFpEF,HFrEF by HRs.There appeared a special "separation phenomenon" showing rates of endpoints were inconsistent with their hazards in patients with HFmrEF compared with HFpEF patients.

Unicellular green alga,Dunaliella salina(D.salina),is a biflagellar alga without cell wall,which is a kind of very important eukaryotic microalga.In the previous study,the research of D.salina focus on the morphology,the mechanism of salt tolerance and ?-carotene,however,with the rapid development of microalgal biotechnology,a lot of work about D.salina was reported in recent years.In the area of molecular biology,the studies of D.salina mainly place emphasis on the cloning and analysis of important functional genes,regulatory sequences,and the expression of foreign genes using D.salina as host.The research advance in these aspects were reviewed.

Objective To assess the clinic application of a new-style automated immunoassay system HISCL ( high sensitivity chemiluminescent enzyme immunoassay ) with high sensitive chemiluminescence substrate CDP-Star?, bind-free separate technology and filter conversion technology.Methods The performance verification test evaluated HISCL′s specification including reproducibility, functional sensitivity, linearity, accuracy, and sensitivity for HBsAg seroconversion.To evaluate the specificity , 1 007 HBsAg-negative specimens , 82 potentially interfering specimens were from conventional specimens in West China Hospital , Sichuan University between October and December of 2014.At the same time, with these results to determine the rate of the specimens that their results are in negative grey zone.259 HBsAg-positive specimens and 27 weakly-positive specimens were tested for the comparison between the HISCL and ECLIA ( electrochemiluminescence immunoassay ) HBsAg quantification.A linear regression model , Pearson′s correlation and Bland-Altman analysis were used as statistical methods.Results The between day and within-lot variable coefficient of two level samples are 1.55%, 2.02%, 0.34%, 1.34%separately.The functional sensitivity of the HISCL HBsAg assay reaches 0.007 IU /ml.There is a good linearity (y=3.262x+0.082,r=0.994; y=2 303.608x-33.006,r=0.999) within range of 0-2 300 IU/ml.HISCL obtain the accurate results for the CAP control material , the agreement rate is 100%.The sensitivity for the detection of HBsAg seroconversion is high.The specificity is 99.91%.The negative grey zone rate is 1.66%.The results of these two methods have good correlation and uniformity , r=0.995, LOA:-0.3 -0.19 log10 IU/ml.Conclusions HISCL HBsAg detection system shows good detection performance.Be of the function of both qualitative and quantitative detection.And the negative “grey zone”specimen rate is low.It is wholly capable of wide linearity and quick assays for quantifying serum HBsAg levels.HISCL could contribute to improve HBsAg quantitative detection process for clinical laboratory.

The human canstatin cDNA was amplified by RT-PCR and then directionally cloned into pU? expression vector. The recombinant pU?-Can vector was connected with the screening marker (bar box), to construct a eukaryotic expression vector called pU?-Can-Bar. This expression vector was introduced into the D.salina by glass beads method. The screening culture of transformants of D.salina was performed in solid media containing 5 ?g/ml PPT, and the analyses of transformants were carried out through PCR and Southern blot. PCR results revealed that specific 700 bp products were detected in the different transformants of D.salina but not in negative control. Southern blot analysis further demonstrated that human canstatin gene was integrated into the D.salina genome. Moreover, the results of genetic stability analyses of transformants demonstrated that canstatin gene was stably inherited in the D.salina transformants. The successful preparation of the D.salina transformants will provide the experimentation evidence for producing canstatin protein cosmically by using the D.salina bioreactor and give a better prophase work basis for clinic application of canstatin protein early.

Objective By comparing the organ system based medical integration teaching mode and traditional teaching mode to evaluate the effect of the integration of curriculum implemen-tation. Methods Through a questionnaire survey of 63 students who implement integrated curriculum and 183 students who are not implementing integrated curriculum as well as 76 teachers, we evaluate students' emotional, cognitive and motor skills, using SPSS statistical analysis, chi-square test. Results In the affective domain, most of the teachers thought the experimental class was superior to the com-mon one in learning interest, lifelong learning and independent learning, critical thinking, the contrast of the two classes were P=0.000, P=0.031 and P=0.001 respectively, all of significant difference. In the cognitive domain, the contrast of the two classes in memory, understanding and application were P=0.000, all of significant difference. The experimental class has high degree of recognition. In the psychomotor domain, more than 55.3%(42/76) of the teachers thought that the experimental class was superior to the common class. According to the students' questionnaire survey, the contrast of the two classes in clinical operation skills, Interpersonal communication skills were P=0.077, P=0.031 respec-tively. There was no statistically significant difference. Conclusions The integrated curriculum teach-ing model can greatly promote students' abilities in most areas such as interest in learning, lifelong learning awareness, clinical thinking ability; interpersonal communication skills etc. In some respects the differences remains to be further studied such as memory of knowledge, systematic knowledge, and clinical operation skills, etc.

Objective To study the anti-fatigue effect of Cynomorium songaricum flavone(CSF)on old rats.Methods50 old male Wistar rats were randomly divided into the control group(no swimming,no drugs),single swimming group(swimming,given saline by gavage),and three swimming plus CSF groups(swimming,given CSF 20 g/kg weight,10 g/kg weight and 5 g/kg weight respectively),total five groups with 10 animals in each group.Animals swam with free swimming in endless cycles water 30 minutes once every day for 10 days.The level of monoamine oxidase(MAO) and glutathione peroxidase(GSH-px) in blood of animals were examined by MAO kit,GSH-px kit and ultraviolet spectrophotometer at 11th day.ResultsCompared with single swimming group,the body weights of swimming plus CSF groups increased significantly by 12.9%,80.6% and 200% respectively(P<0.01);swimming times before sinking increased by 19.4%,29% and 48.4%;sinking times of each rat(time/10 min) decreased by 17.8%,43.2% and 72.9%;total swimming times increased by 2.8%,7% and 29.6% respectively(P<0.01);MAO decreased by 60%,69.8% and 80.5%,GSH-px increased by 465.3%,563.8% and 635% respectively(P<0.01).ConclusionCSF shows anti-oxidative and anti-fatigue properties and can be given as prophylactic/therapeutic supplements for increasing antioxidant enzyme activities and preventing lipid peroxidation during strenuous exercise.

Objective To observe changes of left ventricular function and the level of autophagy after treatment with trimetazine in rats with heart failure after myocardial infarction(MI). Methods Twenty healthy male Wistar rats with the ligation of the proximal part of the left descending branch were randomly and equally allocated into two groups,model group (M group) and trimetazine group (Q group). A sham group (S group) was made up by 10 sham-operated rats. Rats of trimetazine group were given trimetazine(15 mg/kg)once a day for 4 weeks.Then left ventricular function was measured by echocardiography,and hemodynamics was evaluated by Millar pressure-volume system.Serum levels of NT-proBNP and hs-TnT were tested by ELISA.Pathological changes and fibrosis of myocardium were observed by HE and Masson staining.The myocardial apoptosis level was observed by TUNEL, and expressions of autophagy related protein and gene in myocardial tissue were detected by Western blot assay and RT-PCR. Results Trimetazine treatment significantly improved left ventricular dilatation and dysfunction in rats with myocardial failure. Trimetazine treatment also significantly improved pressure overload and the compliance decrease of left ventricular in rats with heart failure after myocardial infarction. Trimetazidine reduced the edema,necrosis and myocardial fibrosis of cardiac myocytes in rats with heart failure.The results from ELISA showed that serum levels of NT-proBNP and hs-TnT were significantly lower in the trimetazine group than those of model group.Compared with model group,the cardiomyocyte apoptosis decreased significantly in the trimetazine group.The results from Western blot assay and RT-PCR showed that autophagic flow of myocardium was increased remarkably in the trimetazine group than that of model group. Conclusion Autophagy has a protective effect on myocardial cells. Trimetazine can improve cardiac function through up-regulation of autophagy in cardiomyocytes in MI rats with heart failure.

Background:Successful antiretroviral therapy (ART) has been demonstrated to be effective in reducing the infectivity of human immunodeficiency virus (HIV).We conducted a study to predict the potential effect of ART on the spread of HIV in Chaoyang District,Beijing,China,using the Asian Epidemic Model (AEM).Methods:The AEM baseline workbook was used to determine the current infection status and to project the future spread of HIV under current conditions.We changed the input on the ART coverage from 2014 to 2025 and also modified the treatment eligibility in the AEM intervention workbook,in order to allow for analysis of the projected downstream impact of ART.Results:By gradually increasing the ART coverage rate from 29.7％ (rate of 2013) to 40.0％,50.0％,60.0％,70.0％,80.0％,and 90.0％ (at CD4+ ≤350 cells/μl),and by changing the dates of coverage from 2014 to 2020,the number of new infections showed a cumulative decline of 0.60％,1.59％,2.94％,5.33％,9.32％,and 14.98％,respectively.After 2020,the projected rates of infection rebounded slightly,so with the exception of the years with very high coverage (90.0％),new infections continued to decrease.When we changed the initial threshold of therapy to CD4+ cell counts ≤500 cells/μl,new infections decreased 6.00％,11.64％,15.92％,2 1.11％,26.92％,33.05％,and 38.75％,respectively,under varying ART coverages.Conclusion:Our study demonstrates that the early initiation of ART for people living with HIV/acquired immune deficiency syndrome (AIDS) has a positive effect in slowing the spread of HIV.