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.

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.
Antiretroviral Therapy, Highly Active ; Cells, Cultured ; Drug Resistance, Viral ; HIV Integrase Inhibitors ; pharmacology ; HIV-1 ; drug effects ; physiology ; Heterocyclic Compounds, 3-Ring ; pharmacology ; Humans ; Virus Replication ; drug effects

Adult ; Biomarkers, Tumor ; metabolism ; Calbindin 2 ; Female ; Follow-Up Studies ; Humans ; Mesothelioma ; metabolism ; pathology ; surgery ; Mucin-1 ; metabolism ; Peritoneal Neoplasms ; metabolism ; pathology ; surgery ; S100 Calcium Binding Protein G ; metabolism

Although small molecule drugs (SMD) are still mainstream for the treatment of diseases, large molecule biologicss of many advantages, pose a challenge to the further discovery and use of SMD. The advantages of SMD are the convenience of oral administration and good patient compliance. However, the challenge with SMD is to integrate the PD, PK, selectivity and safety into a chemical structure. Because of their small size and surface area they often bind to various proteins, and off-target actions can cause adverse reactions. In this sense, selectivity is critical. Based upon target as the core to construct a chemical structure, it is necessary to consider the requirements of all the attributes, but achievement of the full-dimensional optimization is difficult. Modern drug discovery has been greatly enhanced by molecular biology and structural biology, and new strategies and technologies have emerged, which have created many successful medicines. For example, under the guidance of structural biology, covalent binding drugs connect moderate "electrophilic warheads" to the appropriate positions of molecules, and upon binding to their targets the electrophiles are irreversibly linked to the target by covalent bonds. Molecular biology can be directly applied to the development of antibody-coupled drugs (ADC). The antibody (A) acts as a carrier and a guide (for PK), and carries toxic molecules (D) into cancer cells, thus playing a killing role (for PD). The separate pharmacodynamic and pharmacokinetic entities are coupled (C) by linkers. PROTACs are also bifunctional molecules, which recruit a target protein and ubiquitin ligase E3 to form a ternary complex, which then acts as a catalyst to ubiquitinate the target protein and lead to degradation by the proteasome. In addition, in recent years, the combination of two fixed-dose drugs has improved selectivity, safety, and long-term benefit with many severe diseases, and can be regarded as an innovative strategy of physical combination. This review discusses some successful examples to briefly present the principles from the perspective of medicinal chemistry and therapeutic application.

Objective To explore nursing methods of postoperative patients with brain stem tumor complicated with stress hyperglycemia. Methods The medical and nursing measures of 56 postoperative patients with brain stem tumor complicated with stress hyperglycemia were analyzed retrospectively. Results Among 56 cases, 48 cases were clinically cured, 6 cases was improved, 2 cases died of multiple organ failure. Conclusions It is especially important to intensify insulin therapy, necessary to closely observe the patients' consciousness, pupils and the change of vital signs. Meanwhile, strengthening nursing on common complications such as infection and gastrointestinal hemorrhage, and paying more attention to patients' dietary, mental state and rehabilitation are also important measures.

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.

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.