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 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.

To determine the key influencing factors on formation of prasugrel hydrogen sulfate polymorph during the reactive crystallization of prasugrel free alkali and sulfuric acid, clarify the rule of the influences of solvent, temperature, and supersaturation, and reveal the mechanism of prasugrel hydrogen sulfate polymorph formation.

Based on combined application of X-ray diffraction spectroscopy (PXRD), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA), this study focused on the crystallization thermodynamics and reactive crystallization process of prasugrel hydrogen sulfate. The stability relationship between the polymorphs of prasugrel hydrogen sulfate and the influencing rule of polymorph formation during reaction crystallization were investigated.

It was shown that solvent and supersaturation were the key factors affecting the formation of prasugrel hydrogen sulfate polymorphs.

Prasugrel hydrogen sulfate form Ⅰ and form Ⅱ are monotropically related systems, and form Ⅱ is a stable form. Solvent plays a leading role in the formation of prasugrel hydrogen sulfate polymorphs, and the formation of polymorphs in butanol obeys to the Ostwald's rule.

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 retrospectively analyze the cardiac adverse events and death cases of EGFR inhibitors through data mining of FDA adverse reaction reporting system (FAERS), so as to better understand the safety of EGFR inhibitors.

The data in a total of 36 quarters in FAERS database from 2013 to 2021 were mined and analyzed by reporting odds ratio (ROR).

A total of 30 728 493 adverse events were reported in FAERS database from 2013 to 2021, including 735 693 cardiac adverse events. The effective signals were cetuximab [ROR=1.16, 95%CI (1.07,1.26)], rituximab [ROR=2.94, 95%CI (1.61,5.36)], dactinib [ROR=3.73, 95%CI (2.10,6.62)], and ositinib [ROR=1.55, 95%CI (1.44,1.66)]. McAbs were more likely to cause tachycardia. All heart-related effective signals of TKIs contained pericardial effusion. The significant death signals were panizumab [ROR=1.71, 95%CI (1.54,1.89)], gefitinib [ROR=2.93, 95%CI (2.64,3.25)], erlotinib [ROR=6.72, 95%CI (6.54,6.91)], afatinib [ROR=1.30, 95%CI(1.17,1.45)], dactinib [ROR=14.24, 95%CI (11.27,17.99)], and ositinib [ROR=15.03, 95%CI (14.53,15.54)].

EGFR receptor inhibitors can cause adverse cardiac events with serious outcomes and increase the risk of death, which are worthy of clinical attention. Due to the limitations of database and detection methods, long-term data are still needed to verify these results to further understand the safety of EGFR inhibitors.