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.

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.

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.

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.

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

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

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.

At present, the prevalence of heart failure (HF) is still high in China, and its mortality and readmission rate have no downward trend. Therefore, the mechanism of its occurrence and development needs to be explored. In recent years, it has been found that about 13%-15% of HF patients have subclinical hypothyroidism (SCH), which can lead to cardiac systolic and diastolic dysfunction, thus promoting the occurrence and development of HF. At present, the curative effect of patients with mild elevation of thyroid stimulating hormone (TSH) level in HF patients with SCH is not clear, and a large number of prospective studies are still needed. In addition, in the complications of HF, SCH is the only disease that can reverse cardiac function after treatment. Therefore, this paper summarizes the mechanism of SCH in the occurrence and development of HF, and provides the basis for the formulation of clinical HF treatment strategies and the evaluation of prognosis.

ObjectiveTo study the factors which affect the nurses' implementation of cardiac rehabilitation. MethodsData of 134 nurses who worked or are working in cardiology ward in No.1 and No.2 hospital of China Medical University was analyzed by using descriptive and inferential statistics.ResultsThe overall barriers is at a moderate level. The types of the barriers in order of mean score were no formal rehabilitation program, lack of knowledge, lack of facility, lack of support, and lack of understanding. Conclusions In order to improve the motivation of nurses to implement cardiac rehabilitation nursing, something must be done to improve nursing practice , nursing administration, and nursing education.