To analyze the monosaccharide composition of human erythropoietin by cIEF-MS.

The cIEF peak was obtained after cIEF detection, and each peak was detected by MS to obtain the high resolution mass spectral molecular weight. After deducting the protein molecular weight, the redundant molecular weight was compared with the molecular weight combination database of monosaccharide residues (accuracy being about 0.01%) to obtain a series of monosaccharide combination manners with basically consistent mass, and the rationality of monosaccharide quantity and the relationship between monosaccharides were analyzed.

Ten cIEF peaks were obtained by cIEF detection, and no less than 32 peak mass numbers were obtained by MS detection. After comparison, a series of monosaccharide combination forms corresponding to each mass number were obtained. Only the combination form with the highest ion number P3 was listed in this paper. The effectiveness analysis results showed that the most extensible combination manners were 19 GlcNAc/GlaNAc residues, 22 Man/Gla residues, 12 Neu5Ac residues and 3 Fuc residues.

The monosaccharide combination manner of human erythropoietin protein glycosylation chain was obtained, which laid a foundation for the further analysis and characterization of complete protein glycoforms.

To investigate the physical and biological stability of PEG-modified liposome influenza vaccine lyophilized powder by influencing factor experiment and accelerated experiment and predict the validity period.

High temperature influencing factor test was carried out at (40±2) ℃, and accelerated test was carried out at 4 ℃ and (25±2) ℃. Physical stability was evaluated by appearance, particle size, encapsulation rate and stability coefficient. Spleen lymphocyte proliferation test and hemagglutination inhibition test were used to evaluate the biological stability, in which the stimulation index (SI) and antibody titer ratio (HI) were used as indexes. The validity period was calculated by using the classical constant temperature method and Arrhenius formula.

In the influencing factor experiment, the particle size and stability coefficient increased and the encapsulation rate decreased gradually after placing PEG2000 (3000/6000)-modified liposome influenza vaccine freeze-dried powder at (40±2) ℃ for 20 days. On the 10th day, the SI value of each PEG group was significantly bigger than that of the original solution group (P<0.05). The titer ratio of antibody before and after immunization was >4 for all PEG groups; on the 20th day, the SI value of each PEG group was significantly smaller than that of the original solution group (P<0.05); the antibody titer ratio of each PEG group after and before immunization was less than 4. In the accelerated experiment, three batches of PEG6000-modified liposome influenza vaccine lyophilized powder were placed at 4 ℃ and (25±2) ℃ for 3 months, the sample was stable at 4 ℃ with minor changing in particle size, encapsulation rate and stability coefficient, while at (25±2) ℃ the particle size and stability coefficient gradually increased, the encapsulation rate gradually decreased. There was significant difference in SI value between PEG6000 group and stock solution group under 4 ℃ storage condition (P<0.05), and no significant difference under (25±2) ℃ storage condition. For PEG6000 group, the ratio of antibody titer after and before immunization were ≥4 under both storage condition of 4 ℃ and (25±2) ℃. For the validity period prediction, the values of decomposition velocity constants K at 25 ℃, 30 ℃, 35 ℃ and 40 ℃ were 1.039×10^-3, 2.649×10^-3, 3.574×10^-3, and 4.868×10^-3 d^-1, respectively. The regression equation of lnK to 1/T was as following: lnK=20.195-8 148.5/T (r=0.917 9).

PEG-modified liposome influenza vaccine freeze-dried powder has good stability at (40±2) ℃ for 10 days, PEG6000-modified liposome influenza vaccine freeze-dried powder has good stability at 4 ℃ and (25±2) ℃ for 3 months. It is estimated that PEG6000-modified liposome influenza vaccine can be stored for 2.2 years, 3.3 months and 24 days at 4 ℃, 25 ℃ and 37 ℃ respectively.

To explore the predictors of the clinical response to tofacitinib in rheumatoid arthritis (RA).

The clinical data of a cohort of 256 RA patients regularly followed up at the Department of Rheumatology and Immunology, Peking University People's Hospital were analyzed, among whom 121 patients with DAS28-ESR≥3.2 were treated with tofacitinib. Data were collected from patients starting to receive tofacitinib and at 6-month follow-up to evaluate the remission rate and analyze the predictors for achieving Boolean 3v remission.

Out of 121 patients treated with tofacitinib, 104 patients (86.0%) were treated with tofacitinib for more than 6 months and 17 patients changed medication within 6 months, including 10 patients (8.3%) due to poor efficacy and 7 patients (5.8%) for adverse effects. After 6 months of follow-up, the remission rates according to Boolean 3v, DAS28-ESR and CliDR were 72.8%, 57.0% and 44.7%, respectively. The EULAR response rate was 88.6%. Multivariable logistic regression analysis showed that gender, number of conventional synthetic DMARDs resistance and glucocorticoid combination were independent predictors for Boolean 3v remission after 6 months of tofacitinib treatment.

Female patients without glucocorticoids and a small number of conventional synthetic DMARDs resistance tend to get better response to tofacitinib.

To study and analyze the development and vaccination of corona virus disease 2019 (COVID-19) vaccines in four major countries represented by China to understand the current situation of COVID-19 vaccine availability.

The policies and plans of vaccine development in each stage were refined and summarized and then classified and counted according to the approval types and time, and descriptive statistical analysis was carried out on the relevant data from development to vaccination.

Up to March 31, 2022, the effectiveness of 13 COVID-19 vaccines developed by China, the United Kingdom, the United States and Russia were all higher than the minimum standard of the WHO (50%). China had made the largest contribution in terms of supply. In terms of vaccination volume, China had exceeded 3.27 billion doses, ranking the leading position.

Vaccine purchase funds, distribution plan defects, vaccine nationalism, COVID-19 strain variation and other obstacles to effective vaccine access can be ensured and achieved by accelerating research and development, increasing production, fair distribution and expanding vaccination.

To identify new potential xanthine oxidase (XO) inhibitors through hierarchical virtual screening.

The pharmacophore model was constructed based on receptor-ligand crystal complex. And a decoy set was used to verify the pharmacophore model. On this basis, the model was used to find potential XO inhibitors from ZINC natural-products database by combining with molecular docking, ADMET prediction and molecular dynamics simulation.

The optimized pharmacophore model contained two hydrogen bond acceptors, two hydrophobic centers, one negative ionizable center and one aromatic ring center. The docking results of the decoy set indicated that the constructed pharmacophore model had high sensitivity and specificity. Molecule ZINC0934445 which was obtained through hierarchical virtual screening was predicted to have good inhibitory activity and drug-like properties. And molecular dynamics simulation results also showed that its binding free energy was better than the positive drug febuxostat.

A variety of computer virtual screening technologies were comprehensively integrated to identify novel XO inhibitors. And one potential active molecule ZINC09344458 was discovered from natural products, which would relieve pain associated with gout. This study provided an alternative method for relevant experimental studies on the development of gout therapeutic drugs.