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.

Objective To establish a high-throughput screening system to obtain key Staphylococcus aureus (S.aureus)secretory proteins which required for S.aureus survival in macrophages.Methods Based on our validated eukaryotic expression vector library of S.aureus secretory proteins,DNA transfection was used to obtain an RAW264.7 macrophage array expressing S.aureus secretory proteins.After the RAW264.7 cells were infected with S.aureus,the extracellular bacteria were removed to observe the intracellular surviving situation of S.aureus.Finally,the screening results were validated by the overexpression and knockout S.aureus of corresponding secretory proteins.Results The optimal transfection dose (1.0 μg/well)of plasmids for RAW264.7,multiplicity of infection (MOI,1 .0 ),and infection time (4 h after removing extracellular bacteria of S.aureus ) were established respectively.To validate the screening results,the corresponding overexpression and knockout strains were constructed.And hypothetical protein and Serine protease E were found to promote the survival of intracellular S.aureus.Conclusion We successfully construct a screening system for key secreted secretory proteins which required for S.aureus surviving in macrophages,which may advance the study of the intracellular surviving mechanism of S.aureus.

Objective To investigate the distribution of B cells in both tumor and non-tumor tissues of gastric cancer patients,analyze their phenotypic characteristics and explore the impact on T cell proliferation.Methods Immunohistochemical staining was utilized to detect the expression of B cell surface marker CD 19 in tumor and non-tumor tissues from 33 gastric cancer patients.The expression levels of chemokine receptors and immunoglobulin molecules on B cells in both tumor and non-tumor tissues were measured using flow cytometry.Chemotaxis experiments were conducted to examine the role of the CXCL12-CXCR4 axis in B cell chemotaxis.B cells isolated and purified from both tissue types were co-cultured with autologous peripheral T cells to assess their effect on T cell proliferation.Results There were significantly more B cells infiltrated in tumor tissues than those infitrated in the non-tumor tissues of gastric cancer patients(P＜0.01),and CXCR4 was highly expressed on tumor-infiltrating B cells compared with B cells derived from non-tumor tissues(P＜0.05).The Cancer Genome Atlas(TCGA)analysis indicated that the expression level of CXCL12 in tumor tissues was positively correlated with the expression level of CD19 in gastric cancer patients(r=0.15,P＜0.01).And the expression level of CXCL12 in tumor tissues of the gastric cancer patients was also positively correlated with the number of B cells infiltrated in tumor tissues.Chemotaxis experiments confirmed that the CXCL12-CXCR4 axis was involved in promoting B cell chemotaxis(P＜0.05).Although B cells in tumor and non-tumor tissues had similar levels of IgM,IgG,and IgA expression,tumor-infiltrating B cells significantly inhibited the proliferation of T cells when compared with B cells derived from non-tumor tissues(P＜0.01).Conclusion There are more B cells infiltrated in gastric cancer tissues,which may be recruited to tumor tissues through the CXCL12-CXCR4 axis,and then inhibit T cell proliferation to promote the progression of gastric cancer.

Objective To explore the mechanism which drives nimbolide(NIM)in treating acute pneumonia caused by Staphylococcus aureus(S.auteus).Methods A mouse model of acute pneumonia caused by S.auteus was constructed through endotracheal intubation.After NIM treatment,the survival rate was observed,the amount of bacteria in the lung was tested by plate culture,and the expression of inflammatory cytokines in the lung tissues was detected with ELISA.After primary cultured peritoneal macrophages(PM)were infected with S.auteus,the effect of NIM on the expression of inflammatory cytokines and activation of inflammatory pathway were studied with ELISA and Western blotting,respectively.The effect of RNF114 knockdown by lentiviral shRNA infection on inflammation responses in PM was explored with ELISA and Western blotting.Results Acute infection of S.auteus in the lung could cause acute death in the mice,while NIM treatment significantly improved the survival rate and down-regulated the levels of inflammatory cytokines in the lung.However,it had no effect on the lung colonization of S.auteus in the short term.The results of in vitro experiments indicated that NIM may regulate RNF114 function to down-regulate the phosphorylation level of ERK,inhibit the activation of MAPK pathway,and thus suppress the expression of inflammatory cytokines.Conclusion NIM may inhibit the activation of MAPK pathway by regulating the function of RNF114,and thus suppress the expression of inflammatory cytokines in the lung,and finally inhibit the death of mice with acute pulmonary hyperinflammation caused by S.auteus.

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.

Biotechnological Pharmaceutics is a compulsory course for biotechnology undergraduates in our school. We designed and implemented an elective course named Structural Biology to help students master technological principles through practice. This elective course included in-classroom lectures and experiments; during which we encouraged students to work together, and design, prepare, implement, and complete projects; examination score of Biotechnological Pharmaceutics was used to assess learning outcomes. The results showed that students who took this course gained higher score in the examination, indicating that the elective course is effective to improve the learning effect of Biotechnological Pharmaceutics for biotechnology undergraduates.

With the rapid development of modern equipment and widespread familiarity with the relative knowledge, endoscopic ear surgery has attracted many oto-surgeons and is becoming more popular in primary hospitals in China. Standardized management of perioperative period in this field can help surgeons shorten the learning curve and avoid potential complications in endoscopic ear surgery. In this article, the management technique was introduced in detail, covering five main aspects including handling of related in-struments, preoperative examination and preparation, informed consent, preparation for patients and operation room setup. Extra focus was placed on the manipulation and resolution of possible difficulties during the procedure.

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.

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 study the effect of Yiqihuoxue Paishiyin combined with levofloxacin on renal calculus and inflammatory state. Methods 76 patients with kidney stones in our hospital from February 2015 to September 2016 were selected as the study object,and they were divided into control group 38 cases and observation group 38 cases by the method of random number table,then the control group were treated with levofloxacin, the observation group were treated with supplementing qi,promoting blood circulation and removing stones combined with levofloxacin,then the clinical effective rates,serum fever and pain related inflammatory factors before and after the treatment of two groups were analyzed .Results The total effective rates of observation group with different stone diameters and stone locations were all higher than those of control group,the serum fever and pain related inflammatory factors at different time after the treatment were all lower than those of control group , the differences were all significant ( P <0.05 ) . Conclusion Yiqihuoxue Paishiyin combined with levofloxacin treatment of kidney stones in patients with significant effect , can effectively control the body's inflammatory state, improve the level of inflammatory factors.