Hie expression of hypoxia-inducible factor- 1a ( HIF-1a) is one of the important factors that cause most solid tumors rapid growth in hypoxic microenvironment, HIF-1a plays an important role in tumor angjogenesis, cell proliferation, metastasis and apoptosis. Similarly, HIF-1a also plays important biological roles in the occurrence and progression of digestive system carcinomas, such as esophagus cancer, stomach cancer, colon cancer, liver cancer and pancreatic cancer. HIF-1a can be used as one of the important molecular markers in prevention and treatment of gastrointestinal cancers.

General anesthetics are widely used in pregnant women,gravidas and infants.In the basic studies of rodents,mammals and non-human primate,general anesthetics can cause neurotoxicity,neuroapoptosis and damage neurodevelopment on the developing brain.Therefore,To explore protective measures and mechanism of anesthetic neurotoxicity is of great significance for formulating clinical anesthesia plan,guiding clinical obstetrics and pediatric anesthesia.This article reviewed the progress of ameliorating the neurotoxicity of general anaesthetics on developing brain including anesthetic assistants,hormone drugs,plant extracts,nutritional components and others.

Objective To develop, validate and preliminarily apply a high-performance liquid chromatography(HPLC)-charged aerosol detector(CAD) method for the quantitative analysis of polysorbate 80 in recombinant protein drug romiplostim, in order to provide a reference for the quality control of recombinant protein drug preparations.Methods The HPLCCAD determination method for polysorbate 80 content was developed by screening the mobile phase and optimizing the elution gradient and CAD parameters. The specificity, repeatability and accuracy of the method were validated, and the limit of detection(LOD), limit of quantitation(LOQ) and linear range were determined. The content of polysorbate 80 in two batches of romiplostim samples was determined by using the developed method.Results HPLC-CAD conditions after method optimization were as follows: Acclaim Surfactant Plus column(150 mm × 4. 6 mm, 3 μm) was adopted, and the column temperature was 25 ℃. The 0. 1% formic acid in water and 0. 1% formic acid in isopropanol were used as mobile phase A and B respectively, with a flow rate of 0. 6 mL/min and a gradient elution(0 min 80% A, 1. 8 min 80% A, 2. 0 min66. 5% A, 3. 0 min 66. 5% A, 3. 5 min 0% A, 8. 5 min 0% A, 9. 0 min 80% A, 15. 0 min 80% A). The injection volume was10 μL. The evaporative temperature for CAD was 50 ℃ and the power function value(PFV) was 1. 25. There was no interference of other chromatographic peaks in the sample matrix and blank solution in this method. The RSDs of peak area for repeatability at low(10 mg/L), medium(50 mg/L) and high(80 mg/L) concentrations were 4. 32%, 1. 97% and 3. 46%, and the mean spike recoveries were 95. 7%, 99. 0% and 98. 9%, respectively. Polysorbate 80 had a good linear relationship in the concentration range of 5. 0-100. 0 mg/L(R2= 1. 000 0), and the LOD and LOQ in the method were 1. 0 and 2. 0 mg/L respectively. The content of polysorbate 80 detected by the developed method was 33. 20 and 32. 28 mg/L in two batches of romiplostim samples respectively.Conclusion The developed HPLC-CAD method for the determination of polysorbate 80in romiplostim has high sensitivity, specificity, repeatability and accuracy, which can be used for the determination of polysorbate 80 in the quality control of recombinant protein drugs.

Objective To characterize the capsid proteins of recombinant adeno-associated virus 6(rAAV6)vectors by reversed phase liquid chromatography-mass spectrometry(RPLC-MS),including primary structure and post-translational modification(PTM).Methods The mobile phase A consisted of 0. 1% aqueous solution of difluoroacetic acid(DFA),while the mobile phase B was 0. 1% DFA acetonitrile solution. The column temperature was maintained at 80 ℃,and the gradient elution lasted for 10 min(0→10 min,mobile phase B 15%→45%). The ESI-Q-TOF mass spectrometry detection operated in positive ion mode with the scanning range of 400-4 000 m/z,the scanning frequency of 2 Hz,the cone voltage at 80 V,the capillary voltage at 3. 0 kV,and the ion source temperature at 120 ℃.Results The measured relative molecular mass of the AAV capsid proteins VP1,VP2,and VP3 was 81 255. 9,66 062. 9,and 59 488. 6,respectively. The deviations from the theoretical values were 8. 1 ppm for VP1,3. 8 ppm for VP2,and 36 ppm for VP3. Mass peptide profile analysis of the enzymatically digested rAAV6 sample indicated a sequence coverage of about 89% with detected PTMs mainly including deamidation,N-terminal acetylation,ubiquitination,and phosphorylation;no glycosylation modification sites were found. Tandem mass spectrometry confirmed the N-terminal and C-terminal sequences of the rAAV6 capsid protein as well as the N-terminal PTM.Conclusion The complete relative molecular mass of rAAV6 capsid protein was analyzed by RPLCMS technique,and the PTM of rAAV6 capsid protein was analyzed by tandem mass spectrometry at the peptide level,which has a certain significance for the quality control of AAV gene therapy products and the improvement of production process.

Objective To evaluate the removal efficiency of chromatography process for impurity proteins[IFN-related proteins and host cell proteins (HCPs)]in the purification process of human interferon α2b (h IFNα2b) by liquid chromatogra-phyhigh resolution mass spectrometry (LC-HRMS),in order to provide experimental basis for improving the production process of h IFNα2b.Methods The whole protein levels of IFN-related proteins (including deamidated IFN,oxidized IFN and acetylated IFN) and HCPs during the chromatography process of h IFNα2b were analyzed by LC-HRMS,and the h IFNα2b post-translational modification sites and HCPs were detected on the polypeptide levels.Results HCPs could be removed by hydrophobic interaction chromatography (HIC) M column,HCPs,deamidated IFN and acetylated IFN could be removed by anion exchange chromatography (AEC),and oxidized IFN could be removed by HIC (B column).The major acetylation sites (K34,K121,K131 and K134),major oxidation sites (M16,M21,M59 and M148),as well as Q5 and Q21 of major deamidation sites (N45,N156,Q5,Q21,Q46 and Q124) of h IFNα2b were located on the surface of the protein,which were susceptible to environmental conditions and subjected to acetylation and oxidation.Conclusion In the purification process of h IFNα2b,chromatography purification can effectively remove IFN-related proteins and HCPs,which also indicated that LC-HRMS technology can be used for the research of IFN purification process.

This study is to evaluate the HAART pharmacodynamics with dolutegravir as the "anchor" in vitro. A nucleoside reverse transcriptase inhibitors (NRTIs) resistant recombinant virus model (VSVG/HIV-1(RT-D67N,K70R,T215F)) and an integrase inhibitors (INIs) resistant recombinant virus model (VSVG/HIV-1(IN-G140S,QI48H)) were constructed and established. The anti-viral pharmacodynamics was evaluated with drug combinations including two NRTIs along with one INI or one NNRTI. The results showed that the combination with an INI gave a stronger synergism on wild type HIV-1 replication comparing to that with an NNRTI. Comparing the two INIs as the "anchor" for HAART, DTG exhibited an equivalent CI to that of RAL on wild type HIV-1 replication; but a greater synergy than RAL on INI-resistant HIV-1 replication. Besides of the pharmacodynamics results of DTG-based drug combination, the results may contribute to clinical antiviral therapy.

Angioplasty, Balloon, Coronary ; Drug Delivery Systems ; Humans ; Stents

Objective To compare the impact of the mass effects in situ ( MEIS ) of the sella tumor on neuroendocrine function in children and adolescents with craniopharyngioma before surgery. Methods A total of 227 inpatients with craniopharyngioma in Beijing Tiantan Hospital, Capital Medical University, from October 2009 to October 2014, were retrospectively analyzed. These patients were divided into children group ( n = 167 ) and adolescent group(n=60) according to the age at the time of the first diagnosis. The clinical characteristics and damage degrees of neuroendocrine function by MEIS of sella tumor were analyzed and compared between these two groups before surgery. Result (1) Clinical characteristics of neuroendocrine function:Among hypothalamic dysfunctional manifestations, central diabetes insipidus showed the highest percentage(children group 35. 93%vs adolescent group 31. 67%), followed by the abnormal appetite and obesity ( children group 19. 76% vs adolescent group 28. 33%). The incidences of abnormal body temperature regulation, sleeping disorder, personality abnormality, and cognitive abnormality all were less than 5%. There were no statistical significant differences in the aforementioned hypothalamic dysfunction parameters between two groups (P=0. 524). Among pituitary-target glands dysfunction parameters, growth hormonce ( GH )-insulin-insulin like growth factor Ⅰ( IGF-Ⅰ) axis dysfunction showed the highest percentage ( children group 64. 07% vs adolescent group 50. 0%), followed by pituitary-gonad axis dysfunction in adolescent group (53. 33%), hyperprolactinemia ( children group 31. 14% vs adolescent group 43. 33%), pituitary-thyroid dysfunction(children group 22. 16%vs adolescent group 28. 33%), pituitary-adrenal gland dysfunction(children group 20. 36%vs adolescent group 25%). There were no statistical significant differences intheseabnormalpituitary-targetglandaxes(exceptpituitary-gonadaxis)betweentwogroups(P=0.475). (2) Comparison of damage degrees of neuroendocrine dysfunction: The patients with normal neuroendocrine function accounted for 10. 2%in children group and 8. 3%in adolescent group. The patients with 1 to 4 items of neuroendocrine dysfunction accounted for 75. 6%in children group and 73. 3%in adolescent group. The patients with more than 5 items of neuroendocrine dysfunction accounted for 14. 4%in children group and 18. 4%in adolescent group. There were no significant differences between two groups(Z=-1. 63,P=0. 103). Conclusions There were no significant differences in characteristics and damage degrees of MEIS of the sella tumor on neuroendocrine dysfunction between children and adolescents with craniopharyngioma. It suggests that systematical evaluation on hypothalamus-pituitary-targets axis function is very important for reducing the risks of further neuroendocrine dysfunction in young patients with craniopharyngioma after surgery.

The important role of library in reading popularization was elaborated, with the main ways for reading popularization and the principal information literary education methods for reading popularization librarians listed, including learning of professional knowledge and skills, training of career virtue, and reading brand popularization.The training of reading popularization librarians and selection of characteristic brand plans can provide the theoretical basis for library to carry out this innovative service.

Objective:The aims of this study are to detect the apoptosis of cancer cells after a single dose of radiotherapy with 99mTc-HYNIC-annexin V and to investigate the correlation among early apoptosis, radio-therapeutic dose, and radio-sensitivity. Methods:Ten days after respective inoculations of EL4 lymphoma and S180 sarcoma in their right upper limbs, the mice were randomly divided into imaging group (Group One) and observation group (Group Two). In Group One, 99mTc-HYNIC-annexin V was injected via the caudal vein after different doses of irradiation. Approximately 2 h later, clinical imaging was conducted by single-photon emission-computed tomography. The mice were sacrificed to evaluate the bio-distribution of 99mTc in each specimen. Cell count during apoptosis was conducted through the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) method. Observation was conducted in Group Two for 2 weeks after the irradiation. Results:Tumor uptake of 99mTc-HYNIC-annexin V significantly correlated with the number of TUNEL-positive cells, which concordantly increased with the increase of dosage (r=0.892, P=0.000). With the same dose (0 or 8 Gy), the values of%ID/g, T/B, T/M, and TUNEL-positive cell number of EL4 lymphoma were significantly higher compared with those of S180 sarcoma. EL4 lymphoma was entirely minimized after irradiation at 8 Gy. Conclusion: 99mTc-HYNIC-annexin V can detect early apoptosis in vivo in tumors receiving radiation. The irradiation-induced apoptosis in vivo determined with 99mTc-HYNIC-annexin V positively correlates with the curative effect of tumors. The detection of tumor cell apoptosis via 99mTc-HYNIC-annexin V helps estimate radio-sensitivity, and can become a predictive index for radiotherapy.