To investigate the relationship between the morphologic changes and the expression of keratin and proto-oncogene induced by Beta-propiolactone (BPL), we assessed on the expression of keratins (K8, K10, K13) and proto-oncogenes (c-fos, c-jun, c-myc) in human HaCaT cell line. The cells were treated with 0, 0.1, 1 microgram/ml BPL for 2 or 6 hours. Morphologic studies revealed that BPL changed the cells into fibrocyte-shaped, caused highly lobulated nuclei and reduced desmosomes in their number. Findings of immunofluorescence and Northern blotting indicated that BPL consistently decrease expression of K10 representing a normal differentiation marker of keratinocytes, while increasing expression of K8 and K13 associated with a pathologic differentiation. This reagent also up-regulated expression of c-fos and c-jun, and down-regulated expression of c-myc. Together with staining for each keratin or proto-oncogene and DNA content in flow cytometry, BPL increased K8 expression dramatically at S-G2-M phase. The induction of c-Fos at S-G2-M phase appeared within 2 hours, and c-Jun gradually occurred. However, c-Myc was inhibited regardless of phases of cell cycle. In conclusion, these changes caused by BPL demonstrate a close relationship between the morphologic evidence and the altered expression of each keratin and proto-oncogene.
Blotting, Northern ; Cell Cycle ; Cell Line ; Desmosomes ; DNA ; Flow Cytometry ; Fluorescent Antibody Technique ; Humans ; Keratinocytes ; Propiolactone* ; Proto-Oncogenes*

Objective:To explore the therapeutic characteristics of population with gout achieving treat-to-target (T2T) indicators through real-world research and evaluate their safety.Methods:A total of 3 287 patients diagnosed with gout by rheumatologists in 21 first-class tertiary hospitals in 10 provinces, municipalities, and autonomous regions in China from January 2015 to December 2021 were included in this polycentric cross-sectional study. The database included patients′ general information, disease characteristics, and clinical application of traditional Chinese and Western medicine treatment measures. SPSS and Excel software were used for data analysis. Frequency analysis, cluster analysis, and factor analysis were used to summarize the characteristics and rules of treatment measures for patients with gout who achieved the target after treatment. The occurrence of adverse events (AE) was recorded during treatment.Results:After treatment, 691 visits (7%) achieved the serum urate (SUA) target, and the most frequent use of urate-lowering therapy (ULT) was febuxostat, followed by benzbromarone. The most common treatment options were following: GroupⅠ: traditional Chinese medicine (TCM) decoction-TCM external treatment-physical exercise-proprietary Chinese medicine; GroupⅡ: ferulic acid-nonsteroidal anti-inflammatory drugs (NSAIDs); Group Ⅲ: allopurinol-sodium bicarbonate-benzbromarone; Group Ⅳ: glucocorticoid-colchicine; Group Ⅴ: febuxostat. A total of 5 898 visits (60%) chieved manifestations of joint pain VAS scores target, and the most frequently used drug to control joint symptoms was NSAIDs. The frequency of use of drugs to control joint symptoms were 2 118 times (usage rate reached 35.9%), while the frequency of ULT were 2 504 times (usage rate reached 42.5%), which was higher than the joint symptom control drug. The most common treatment options were following: Group Ⅰ: proprietary Chinese medicine-TCM decoction-TCM external treatment-physical exercise; Group Ⅱ: NSAIDs-colchicine hormones; Group Ⅲ: allopurinol, Group Ⅳ: benzbromarone; Group Ⅴ: febuxostat. A total of 59 adverse events occurred during treatment.Conclusion:The proportions of gout patients who reach target serum urate level & good control of joint symptoms are both very low, and ULT and anti-inflammatory prescription patterns are very different from international guidelines, so it is necessary to strengthen the standardized management of gout patients. At the same time, life intervention measures account for a certain proportion of the treatment plans for the T2T population, and further exploration is needed.