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 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.

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.

Cardiac Surgical Procedures ; methods ; Child ; Child, Preschool ; Combined Modality Therapy ; Coronary Aneurysm ; diagnosis ; etiology ; therapy ; Coronary Artery Disease ; diagnosis ; etiology ; therapy ; Coronary Thrombosis ; prevention & control ; Echocardiography ; Humans ; Mucocutaneous Lymph Node Syndrome ; complications ; Platelet Aggregation Inhibitors ; therapeutic use ; Thrombolytic Therapy ; methods ; Troponin I ; analysis

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

Ebola virus, the cause of severe and fatal hemorrahagic fever in humans, belongs to filovirus family. This study was designed to establish a cell-based screening and evaluation system in the pharmacological study of antivirus compounds. Three reporter systems were established with recombinant pseudoviral luciferase of HIV core (pNL4-3.Luc.R(-)E(-)) packed with filovirus glycoprotein (EBOV-Zaire GP/HIV-luc, EBOV-Sudan GP/HIV-luc and Marburg GP/HIV-luc), which are required for virus entry of cells. The level of filovirus entry was determined by the expression of luciferase reporter gene in the infected cells. For screening of filovirus entry inhibitors, the vesicular stomatitis G packed pseudovirions (VSVG/HIV-luc) was used to determine the compound specificity. The results of known filovirus entry inhibitors demonstrated successful establishment of the new model systems, which would be useful in high throughput screening of anti-filovirus drugs in the future.
Antiviral Agents ; pharmacology ; Drug Evaluation, Preclinical ; methods ; Ebolavirus ; drug effects ; physiology ; Genes, Reporter ; Glycoproteins ; genetics ; Hemorrhagic Fever, Ebola ; Humans ; Luciferases ; Viral Proteins ; genetics ; Virus Internalization ; drug effects

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.

BACKGROUND:Calcineurin inhibitors reduce acute rejection rates and improve short-term graft survival in renal transplantation, but its nephrotoxicity associated with long-term use of calcineurin inhibitors remains an important issue. To both avoid exposure to calcineurin inhibitors and maintain effective immunosuppression, immunosuppressive agents such as sirolimus have emerged.
OBJECTIVE:To summarize the research progress of the two main protocols of sirolimus in kidney transplantation (de novo sirolimus-based therapy without calcineurin inhibitors and protocol conversion from a calcineurin inhibitor based therapy to sirolimus).
METHODS:With the key words of“kidney transplantation, sirolimus”in Chinese and in English, respectively, a computer-based search of articles was performed in CNKI (January 2000 to September 2013) and PubMed (January 1996 to September 2013) databases. Articles with the de novo sirolimus-based therapy without calcineurin inhibitors and protocol conversion from a calcineurin inhibitor based therapy to sirolimus were included.
RESULTS AND CONCLUSION:Sirolimus may obtain the advantages of no renal toxicity, anti-tumor and lower incidence of cytomegalovirus infections when compared with calcineurin inhibitors. But not al patients are suitable for sirolimus, and to screen patients strictly is the key of satisfactory clinical results. An appropriate treatment plan, drug monitoring of sirolimus, prevention and treatment of complications are essential features of the use of sirolimus.

OBJECTIVE: To discuss about the strategy of small and medium-sized pharmaceutical enterprises' development.METHODS: According to the analysis of different kinds of small and medium-sized pharmaceutical enterprises and the discussion of competition strategy, this paper brings forward the successful development model of small and medium-sized pharmaceutical enterprises.RESULTS & CONCLUSION: Small and medium-sized pharmaceutical enterprise advanced in technology is a successful development model in future. In order to get the development of this kind of enterprise, we should adjust our tactis in aspects of enterprise and goverment.