Objective To explore the effect and preliminary mechanism of the plant-derived immunostimulatory molecule,ophiopogonin,on enhancing the immune response of a subunit vaccine with the receptor-binding domain(RBD)of coronavirus spike protein as the antigen.Methods CCK-8 assay was used to determine the cytotoxicity of ophiopogonin D'(OPD')on bone marrow-derived dendritic cells(BMDCs).Female Balb/c mice were randomly divided into RBD,RBD/OPD',RBD/Alum,and control groups.The immunization dose was 5 μg of antigen per mouse and 100 μg of adjuvant per mouse,and immunization was carried out according to the intramuscular injection immunization procedure on days 0,21,and 42.The titers of specific IgG and its subtype antibodies were detected by ELISA.The cytokine levels in the supernatant of splenocytes were detected using ELISA.The number of splenocytes secreting IFN-γ was detected by ELISpot.Laser confocal microscopy was employed to observe the uptake of antigen by BMDCs.The phagocytic ability of BMDCs for antigen was quantitatively analyzed by flow cytometry.The mechanism of its enhanced immune effect was preliminarily explored using transcriptomics technology combined with bioinformatics research.Results When the concentration of OPD'was less than 5 μg/mL,the survival rate of BMDCs was 100%.After a single intramuscular injection in mice,except for a slight decrease in body weight,the other biochemical indicators were within corresponding normal ranges.After intramuscular injection immunization of the vaccine,the titers of serum-specific IgG,IgG1,and IgG2a in the RBD/OPD'group were significantly higher than those in the RBD group(P<0.05).Compared with the RBD group,the RBD/OPD'group induced a high-level Th1 cell immune response of IL-1β,TNF-α,and IFN-γ(P<0.01)and had more lymphocytes secreting IFN-γ(P<0.001).Laser confocal microscopy displayed that BMDCs took up more antigens after OPD'treatment,which was further confirmed with flow cytometry in quantitative analysis on antigen uptake rate(P<0.01).Transcriptomics results indicated that there was more significant enrichment of the PPAR signaling pathway in the RBD/OPD'group than the RBD group,suggesting that OPD'may activate the PPAR signaling pathway to exert its adjuvant effect.Conclusion OPD'effectively enhances the immune response of the RBD subunit vaccine,and its action mechanism may be related to the activation of the PPAR signaling pathway.

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal-derived tumors of the gastrointestinal tract. Tyrosine kinase inhibitors (TKIs) are the cornerstone of GIST therapy, but mutations in resistance genes pose many problems for treatment, especially the heterogeneity of KIT resistance mutations. In recent years, with the release of a number of GIST related drug research and experimental results, the great potential of targeted therapy, immunotherapy and combination therapy to treat GIST in different directions has been revealed, providing more therapeutic directions for GIST. This article will review the experimental research and future direction in recent years.

Triple-negative breast cancer is estrogen receptor, progesterone receptor and human epidermal growth factor receptor-2 negative breast cancer. The lack of specific treatment targets, there are few effective therapy for advanced triple- negative breast cancer. This article will review the current progress in drug therapy for advanced triple-negative breast cancer, including chemotherapy, targeted therapy, endocrine therapy and immunotherapy, in order to provide reference for clinical treatment.

Objective To assess the impact of glycemic variability on left ventricular function in patients with acute ST-segment elevation myocardial infarction (STEMI) and type 2 diabetes.Methods Three hundred and three patients with type 2 diabetes and first STEMI between May 2014 and December 2016 in Beijing Anzhen Hospital,Capital Medical University were seclected continuously.All participants' continuous glucose monitoring system (CGMS) parameters,echocardiogram and biochemical characteristics were measured at baseline.According to the level of mean amplitude of glycemic excursion (MAGE) which is the gold indicator to present glycemic variability patients were classified into low MAGE group (n=182) and high MAGE group (n =117).Impact of glycemic variability on left ventricular function in patients with acute ST-segment elevation myocardial infarction and type 2 diabetes were analysed.Results (1) Cardiac function evaluation:The level of left ventricular ejection fraction (LVEF) were significantly lower in high MAGE group than in low MAGE group ((43.8± 7.2) vs.(52.3± 8.5) ％,t =4.912,P＜ 0.001).There were significant differences between the two groups in Killip classification (x2 =49.931,P＜ 0.001).(2) Pearson correlation analysis shows that LVEF negatively correlated with the levels of MAGE(r=-0.367,P＜0.001),postprandial glucose excursion (PPGE) (r=-0.274,P=0.003),Hemoglobin A1c(HbA1c) (r=-0.238,P =0.010),serum highsensitive C-reactive protein (hs-CRP) via logarithmic transformation (r =-0.245,P =0.008) and fasting plasma glucose (FPG) (r =-0.229,P =0.021).Killip classification positively correlated with the levels of MAGE (r =0.301,P ＜ 0.001),PPGE (r =0.228,P =0.022),hs-CRP via logarithmic transformation (r =0.234,P =0.019),H bA 1 c (r =0.195,P =0.041) and FPG (r =0.193,P =0.045).(3) Multiple stepwise regression analysis and multivariate Logistic regression analysis indicated that the level of MAGE was independent risk factor of LVEF (t =-2.279,P =0.005,95％ CI(-3.160 -0.219)) and the level of MAGE was an independent risk factor of Killip classification (Waldx2 =5.673,OR=1.665,95％CI(1.095-2.534),P=0.017).Conclusion Glycemic variability is associated with the presence and severity of left ventricular function in patients with STEMI and type 2 diabetes.

Objective: Positron emission tomography-computed tomography (PET-CT) has been used to quantify inflammatory response in the body. The aim of the present study was to explore the possibility of using this method to evaluate the stability of atherosclerotic plaques and the efficacy of atorvastatin in stabilizing atherosclerotic plaques. Methods: Twenty New Zealand male white rabbits were included and divided into the atorvastatin intervention group and the control group, with 10 rabbits in each group. Rabbits in both groups were fed with a high fat diet for 20 weeks, and treated with thoracoabdominal aortic balloon-pulling to establish atherosclerosis model at the end of the 2nd week. Rabbits in atorvastatin intervention group was given atorvastatin intragastrically once a day. At the 8th week, thoracoabdominal aortic ultrasound was used to detect plaques in all rabbits. Blood was drawn at the 3rd and the 20th week, respectively, to measure blood lipids, high-sensitive C-reactive protein (hs-CRP) and matrix metalloproteinase-9 (MMP-9). At the end of experiment, survival animals were scanned by ¹⁸F-FDG PET-CT, and the average and maximum standard uptake values (SUVmean, SUVmax) of aortic segments were measured. Thereafter, the animals were sacrificed and aortic specimens of rabbits were taken and examined by immunohistochemistry. The pathological indexes were measured and compared. Results: At the end of experiment, the total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), hs-CRP [ (4.58±0.51) ng/ml vs.(5.87±0.66) ng/ml, P<0.01], MMP-9[ (43.93±2.16) ng/ml vs. (50.77±2.32) ng/ml, P<0.01], SUVmean (0.59±0.15 vs. 0.68±0.20, P<0.05) , SUVmax (0.68±0.20 vs. 0.81±0.27, P<0.05) , plaque area [ (0.36±0.24) mm² vs. (0.50±0.34) mm², P<0.05) ] and density of macrophage[ (4.34±1.54) % vs. (5.65±1.89) %, P<0.01] in the atorvastatin intervention group were significantly lower than those in the control group. In contrast, fiber cap thickness of the plaque[ (4.12±0.66) μm vs. (2.96±0.37) μm, P<0.01] in the atorvastatin intervention group was higher than that of the control group, and the difference was statistically significant. The arterial plaque areas were positively correlated with SUVmean (r=0.27, P<0.05) and SUVmax (r=0.43, P<0.01) . Fiber cap thickness was negatively correlated with SUVmean (r=-0.38, P<0.05) and SUVmax (r=-0.47, P<0.01) . The density of macrophage were positively correlated with SUVmean (r=0.52, P<0.01) and SUVmax (r=0.51, P<0.01) . Conclusion ¹⁸F-FDG PET/CT can be used to evaluate the efficacy of atorvastatin by the stability of atherosclerotic plaques.

Objective To investigate the metabolic characteristics of chronic total occlusion (CTO) in different sex elderly patients. Methods A retrospective analysis was performed on three hundred and sixty-two cases from Beijing Anzhen Hospital with CTO,including 226 cases in the male group and 136 cases in the female group. The characteristics of metabolic risk factors were compared and analyzed between the two groups. Results (1)The level of the systolic blood pressure (SBP)((135. 62±19. 67)mmHg vs. (129. 08±14. 13)mmHg), total cholesterol (TC)((4. 39±0. 95) mmol/ L vs. (3. 91±0. 93) mmol/ L)、low density lipoprotein cholesterol (LDL-C)((2. 56±0. 80) mmol/ L vs. (2. 23±0. 70) mmol/ L) in the female group were significantly higher than those of the male group,the differences were statistically significant (t = -2. 594,P = 0. 010;t = -3. 341,P= 0. 001;t= -2. 893,P = 0. 004) . (2) The level of urea acid (UA) ((368. 95±75. 96) μmol/ L vs. (326. 20 ±83. 27)μmol/ L) and ratio of smoking ( 61. 95% ( 140/ 226) vs. 5. 88% ( 8/ 136)) in the male group were significantly higher than those in the female group(t= 3. 440,P= 0. 001;χ2 = 55. 211,P= 0. 000). Conclusion The higher levels of systolic pressure,total cholesterol and low density lipoprotein cholesterol are the metabolic clinical characteristics of elderly female CTO patients,and the elevated uric acid and smoking are metabolic clinical characteristics of elderly male CTO patients.

Objective: To compare the safety of continued warfarin therapy and bridging anticoagulation therapy during hospital stay in patients undergoing percutaneous coronary intervention (PCI). Methods: We retrospectively analyzed patients on warfarin therapy referred for PCI in Beijing Anzhen Hospital from January 2008 to December 2016. The patients were divided into continued warfarin therapy (n=195) or bridging anticoagulation therapy (n=311) groups. After Propensity Score Matching, data from matched patients (n=123 in each group) were analyzed. Bleeding complications and major adverse cardiac events including death, myocardial infarction, target vessel revascularization, and stent thrombosis were assessed. Results: There were no significant difference in the rate of death (2.4%(3/123) vs. 1.6%(2/123),P=0.54), acute myocardial infarction (4.1%(5/123) vs. 4.9%(6/123), P=0.78),re-revascularization (0.8%(1/123) vs. 1.6%(2/123),P=0.16), stent thrombosis (1.6%(2/123) vs. 1.6%(2/123),P=1.00) and stroke between the two groups. Prevalence of minor bleeding complications was significantly higher in the bridging therapy group (15.4%(19/123) vs. 9.8%(12/123),P=0.01). Rate of access-site complications (hematoma:4.1%(5/123) vs. 2.4%(3/123),P=0.20; pseudoaneurysm:2.4%(3/123) vs. 2.4%(3/123),P=1.00; arteriovenous fistula:0.8%(1/123) vs. 1.6%(2/123),P=0.09; and retroperitoneal hematoma:0(0/123) vs. 0.8%(1/123),P=0.23) were similar between the two groups. Conclusion For patients receiving chronic warfarin therapy, the uninterrupted oral anticoagulant treatment is as safe as bridging therapy in PCI patients.

Purpose 18F-FDG PET/CT,pathological and immunohistochemical analysis are adopted to explore the value of PET/CT in the early-stage calcification examination of atherosclerosis in rabbits and effects of Pioglitazone in treating early-stage calcification.Material and Methods Sixteen New Zealand male rabbits were randomly divided into two groups:Pioglitazone group and control group,witheight rabbits in each group.Atherosclerosis model was established.Rabbits in Pioglitazone group received gavage with Pioglitazone and were raised with high-fat diet for 20 weeks.Blood was drawn to exam high sensitivity C-reactive protein and matrix metalloproteinase-9.PET/CT was used to measure mean standardized uptake value (SUVmean) and maximum standardized uptake value (SUVmax).Rabbit aorta received immunohistochemical,the plaque area,density of macrophage,percentage of calcification area and apoptosis index between the two groups were determined and compared.Results On 20 week,high sensitivity C-reactive protein in Pioglitazone group (4.27±0.43 vs.6.51 ±0.91,P＜0.01),matrix metalloproteinase-9 (41.52± 1.99 vs.62.21 ±3.60,P＜0.05),SUVmean (0.55±0.18 vs.0.68±0.21,P＜0.01)and SUVmax (0.70±0.19 vs.0.82±0.30,P＜0.05) were obviously lower than those in control group.Plaque area,density of macrophage,percentage of calcification area and apoptosis index in control group were obviously higher than those in Pioglitazone group.Plaque area of related artery section was positively correlated with SUVmean (r=0.28,P＜0.01) and SUVmax (r=0.25,P＜0.05).Density of macrophage was positively correlated with SUVmean (r=0.50,P＜0.01) and SUVmax (r=0.46,P＜0.01).Percentage of calcification area was positively correlated with SUVmean (r=0.50,P＜0.01) and SUVmax (r=0.47,P＜0.01).Apoptosis index was positively correlated with SUVmean (r=0.61,P＜0.01)and SUVmax (r=0.60,P＜0.01).Conclusion Inflammation and macrophage apoptosis are of great importance in the early-stage of atherosclerosis.18F-FDG PET/CT imaging can be used to assess minor calcification.Pioglitazone can reduce inflammatory level of atherosclerosis of the experimented animals,inhibiting early-stage calcification.

Biotechnological pharmaceutics is an important course for pharmacy undergraduates , however there are many problems in current curriculum design and teaching methods. With the advantage of our platform National Engineering Research Center of Immunological Products, we tried to carry out the teaching reformation based on Excellent Engineer Education and Training Plan. We optimized the curriculum standards and teaching design, highlighted the combination ofBiotechnological pharmaceuticsand Engineering, strengthened the experiment teaching, tried the reformation of teaching method such as flipped classroom and PBL, strengthened the cultivation of innovative thinking and scientific research ability. Our teaching reformation is beneficial to cultivating the compound talents in the field of biotechnological pharmaceutics.

Objective Compared the scan doses of the 64 multidetector CT (64-MDCT) in three different lumbar ac-quisition patterns, to determine the optimized one. Methods The water phantom was scanned by the 64-MDCT, and three groups were divided according to acquisition patterns: group A (128 ×0.625 mm), group B (48 ×0.625 mm), and group C (40×0.625 mm). For every group, the water phantom was scanned for 40 times. The volume of CT dose index (CTDIvol), the DLP and the effective dose were calculated and recorded. One-way ANOVA test was used to compare mean values. Results According to the values of CTDIvol, DLP, and effective dose, the three groups were ordered as follows, group A (128×0.625mm)>group B (48×0.625mm)>group C (40×0.625mm). In group C, the values of effective dose were reduced 17.45%and 10.32%, respectively, in comparison with that in group A and group B. Conclusion The 40×0.625 mm is the optimized pattern which had minimum radiation dose.