Objective:To reduce the immunogenicity of vaccinia virus vector by replacing the D8L region, which is a neutralizing antibody epitope in vaccinia virus, with an exogenous gene.Methods:A gene fragment encoding influenza virus hemagglutinin (HA) was inserted into the D8L region to replace it using homologous recombination technique. Then, a recombinant vaccinia virus influenza vaccine was constricted. A recombinant vaccinia virus vaccine with the TK region expressing HA was used as a control. The expression of HA was validated by Western blot. BALB/c mice were immunized with the vaccines and the serum antibody titers two weeks after each immunization were evaluated by ELISA and hemagglutination inhibition assay. The protective efficacy of the recombinant vaccinia virus was assessed through a challenge experiment.Results:Western blot confirmed the successful expression of HAD8L protein in the constructed recombinant vaccines. ELISA and hemagglutination inhibition assay showed that after the primary immunization, the anti-HA antibody titer induced by the recombinant vaccinia virus with D8L region mutation was slightly higher than that induced by the vaccine with TK region mutation, and the difference was statistically significant with the increase of immunization times ( P<0.05). The recombinant vaccinia virus with D8L region mutation showed significantly lower immunogenicity than the recombinant virus with TK region mutation after the primary immunization, but there was no significant difference between them with the increase of immunization times ( P>0.05). After H1N1pdm challenge, no virus was detected in the mice immunized with the recombinant vaccinia virus with D8L region mutation and the mice showed mild lung inflammation and less tissue damage. Conclusions:This study indicated that inserting exogenous genes into the D8L region of the neutralizing antibody epitope in the vaccinia virus vector could help to reduce the immunogenicity of the vector itself and enhance the immunogenicity of the exogenous genes. This provided a reference for the use of the vaccinia virus vector as a delivery tool in the field of vaccines or gene therapy.

Bioengineering majors require students to acquire excellent abilities of thinking and analyzing complex problems and have high requirements for students' comprehensive practical skills. Because of the professional characteristics, it is necessary to develop students' abilities to solve complex problems via the teaching of a series of experiments. Therefore, it is particularly important to reform the traditional experiment teaching for students majoring in bioengineering to improve the teaching quality, which have great significance for the cultivation of comprehensive talents. In this study, with the advantages of geographical location and resources to cultivate application-oriented innovative talents, the course group of Comprehensive Experiment of Bioengineering has designed the course based on virtual simulation technology in Binzhou University. Taking the experiment of extraction and bioactivity analysis of Suaeda salsa (growing in the Yellow River Delta) polysaccharide in fermentation as a case, we studied the course design idea, experimental process, teaching method and result analysis, and have improved the teaching performance. This case analysis provides new ideas and content reference for the teaching reform of similar courses.
Bioengineering/education* ; Biomedical Engineering/education* ; Humans ; Students ; Technology ; Universities

The clinical translation of stem cells and their extracellular vesicles (EVs)-based therapy for central nervous system (CNS) diseases is booming. Nevertheless, the insufficient CNS delivery and retention together with the invasiveness of current administration routes prevent stem cells or EVs from fully exerting their clinical therapeutic potential. Intranasal (IN) delivery is a possible strategy to solve problems as IN route could circumvent the brain‒blood barrier non-invasively and fit repeated dosage regimens. Herein, we gave an overview of studies and clinical trials involved with IN route and discussed the possibility of employing IN delivery to solve problems in stem cells or EVs-based therapy. We reviewed relevant researches that combining stem cells or EVs-based therapy with IN administration and analyzed benefits brought by IN route. Finally, we proposed possible suggestions to facilitate the development of IN delivery of stem cells or EVs.

With continuous discovery of tumor immune targets and continuous changes in antibody research and development technology, antibody drugs are becoming more and more widely used in clinical practice. However, some targets are not only expressed on tumor cells, but also on red blood cells. Therefore, the clinical application of antibodies against the corresponding targets may interfere with the detection of blood transfusion compatibility, resulting in difficulty in blood matching or delay of blood transfusion. This consensus summarizes the current solutions for the interference of CD38 monoclonal antibody (CD38 mAb) in transfusion compatibility testing. After analyzing the advantages and disadvantages of different methods, polybrene and sulfhydryl reducing agents [dithiothreitol (DTT) or 2-mercaptoethanol (2-Me)], as a solution for CD38 mAb interference in blood compatibility testing, are recommended for Chinese patients, so as to eliminate blood transfusion interference produce by CD38 mAb and further provide a pre-transfusion workflow for clinicians and technicians in Department of Blood Transfusion.

Objective:To explore the influence of organizational management mode and regional medical resource allocation on thrombolysis rate of stroke.Methods:A cross-sectional study was carried out in 61 thrombolytic units distributed at 16 administrative districts of Shanghai to collect information including the number of imaging equipment, neurologists and nurses, hospital organization and management mode, thrombolytic rate, etc. Using SPSS 19.0 statistical software, simple linear regression analysis and chi square test were used to analyze the correlation between related indexes and thrombolysis rate.Results:There was no linear correlation between imaging equipment, human resources and regional thrombolysis rate. The key factor to improve thrombolysis rate was the organizational management of stroke( OR=1.488, 95% CI=1.357-1.631, P<0.001). Conclusions:An effective hospital organization and management model, including the establishment of multi department cooperation, stroke emergency team, stroke green channel, can significantly improve the thrombolysis rate of stroke.

Objective To explore the influencing factors of fear of progression among postoperative elderly patients with prostatic cancer. Methods From December 2016 to December 2017, we selected 404 elderly prostatic cancer patients with surgical treatment of Urinary Surgery in Tangshan People's Hospital as subjects by purposive sampling. All of the patients were investigated with the Fear of Progression Questionnaire-Short Form (FoPQ-SF), Readiness for Hospital Discharge (RHD), the Chinese Version of the M. D. Anderson Symptom Inventory and Family Adaptability and Cohesion Scale Ⅱ (FACES Ⅱ). Binary Logistic regression was used to analyze the influencing factors of fear of progression among postoperative elderly patients with prostatic cancer. Results The total of 404 elderly prostatic cancer patients were divided into two groups according to FoPQ-SF, 202 patients with the score of FoPQ-SF less than or equal to 34 in control group and 202 patients with the score of FoPQ-SF more than 34 in case group. There were statistical differences in ages, family support, clinical stages, scores of Gleason, symptom distress and readiness for hospital discharge of patients between two groups (χ2=10.164, 24.762, 21.083, 21.052, 21.915, 25.783;P＜ 0.05). Logistic regression analysis showed that the influencing factors of fear of progression among postoperative elderly patients with prostatic cancer included ages, family support, readiness for hospital discharge, symptom distress and scores of Gleason (P＜ 0.05). Conclusions Fear of progression among postoperative elderly patients with prostatic cancer is affected by many factors. Improving patients' readiness for hospital discharge will help to lower the fear of progression of patients.

Objective To detect the changes of 25-hydroxy vitamin D (25-OH-D) and blood calcium concentrations in the serum of prostate cancer (Pca) patients with bone metastases,and to analyze the correlation between bone calcium metabolism and bone metastasis of prostate cancer.Methods The 35 untreated prostate cancer patients without bone metastases,30 patients with bone metastasis of prostate cancer,and 30 healthy controls were selected,and fluorescent immune chromatography was used to determine the content of 25-OH-D,the Azo arsenic method was used to detect the blood calcium level,and ROC curve was used to analyze the value of two indexes in diagnosing prostate cancer bone metastases.Results The blood calcium content in bone metastasis of prostate cancer group was significantly higher than the other groups (P ＜ 0.05),and the prostate cancer group had a higher blood calcium content than healthy controls (P ＜ 0.05).For 25-OH-D content,bone metastases of prostate cancer group was significantly lower than the other groups (P ＜0.05).25-OH-D level showed a negative correlation with blood calcium in each group (r =0.628,P ＜ 0.05).The ROC curve showed levels of blood calcium and 25-OH-D in the diagnosis of bone metastases of prostate cancer were 0.763 and 0.712.Conclusion The high blood calcium and low vitamin D levels may be an effective predictor for bone metastases of prostate cancer.

Objective To detect the changes of 25-hydroxy vitamin D (25-OH-D) and blood calcium concentrations in the serum of prostate cancer (Pca) patients with bone metastases,and to analyze the correlation between bone calcium metabolism and bone metastasis of prostate cancer.Methods The 35 untreated prostate cancer patients without bone metastases,30 patients with bone metastasis of prostate cancer,and 30 healthy controls were selected,and fluorescent immune chromatography was used to determine the content of 25-OH-D,the Azo arsenic method was used to detect the blood calcium level,and ROC curve was used to analyze the value of two indexes in diagnosing prostate cancer bone metastases.Results The blood calcium content in bone metastasis of prostate cancer group was significantly higher than the other groups (P ＜ 0.05),and the prostate cancer group had a higher blood calcium content than healthy controls (P ＜ 0.05).For 25-OH-D content,bone metastases of prostate cancer group was significantly lower than the other groups (P ＜0.05).25-OH-D level showed a negative correlation with blood calcium in each group (r =0.628,P ＜ 0.05).The ROC curve showed levels of blood calcium and 25-OH-D in the diagnosis of bone metastases of prostate cancer were 0.763 and 0.712.Conclusion The high blood calcium and low vitamin D levels may be an effective predictor for bone metastases of prostate cancer.

Objective To filter appropriate mouse model for avian influenza viruses with different pathogenicity.Methods Two varieties mice (C57BL/6 and BALB/c) were anesthetized with ketamine and inoculated intranasal with highly pathogenic avian influenza virus H7N9 and low pathogenic avian influenza virus H9N2 in 50 μl PBS,or mock inoculated with PBS to serve as controls.The mice were observed daily including clinical symptoms body,weight and mortality.The pulmonary histopathological changes and viral load were also monitored.Results Just one day after the viral inoculation,H7N9 and H9N2 infected mice strains all showed reduced activity,ruffled fur and obvious body weight loss.The body weight loss nadir in BALB/c mice (63.80％ for H7N9/BALB/c;66.35％ for H9N2/BALB/c) were lower comparing to the corresponding viruses infected C57BL/6 mice (68.96％ for H7N9/C57BL/6 and 87.57％ for H9N2/ C57BL/6 respectively).In addition,there were some obvious pulmonary oedema,haemorrhage and typical pulmonary interstitial inflammatory lesions in the lung tissues.The peak viral load in H7N9/C57BL/6 group (1.02 × 105 copies/ml) was 12 folds higher than that in H7N9/BALB/c group (8.7 × 103 copies/ml).But on the contrary,the peak viral load in H9N2/BALB/c group (2.86 × 104 copies/ml) was 5 times of that in H9N2/C57BL/6 group (5.94 × 103 copies/ml).Conclusions Pathogenic characteristics caused by different virulent avian influenza viral strains could be more clearly differential represented in C57BL/6 mice model,and thus it is more suitable for the comparative study between different pathogenic avian influenza viruses.It also reconfirmed that the different pathological changes and clinical outcomes of avian influenza viruses/mice infection models were associated not only to the different biological characteristics of inoculated virus strains,but also to hereditary characters of host mice strains.

The paper analyzes the current status and existing problems of citation retrieval work, puts forward the design principle, overall structure and function of cited references integration tools, demonstrates the key technologies of system realization.An integrated retrieval platform for online literature citations is constructed for the following functions:one-stop retrieval of various citation databases, automatic removal of duplications, so as to reduce the burden of staffs and improve efficiency effectively.