ABSTRACT
Objective To analyze the risk factors of bleeding in elderly patients with peptic ulcer disease (PUD) and its correlation with Helicobacter pylori (Hp) infection, and to provide a theoretical basis for clinical diagnosis and treatment of elderly patients with PUD bleeding. Methods A total of 418 elderly PUD patients admitted to our hospital from June 2019 to June 2020 were selected. The 13C-urea breath test was used to determine HP infection. PUD patients were divided into observation group (n=87, bleeding) and control group (n=331, no bleeding). Age, sex, ulcer number, ulcer location, ulcer stage, ulcer diameter and other clinical data were collected. Univariate analysis and logistic regression were used to analyze the risk factors of bleeding in elderly PUD patients. The Forrest classification was used to evaluate the severity of PUD bleeding patients. Pearson correlation analysis was performed between Forrest classification and Hp infection in elderly PUD bleeding patients. Results There were statistically significant differences between the two groups in the course of disease, PUD history, NSAIDs application/ulcer number, ulcer diameter, ulcer location, ulcer stage, Hp infection and NSAIDs application (P<0.05). Multivariate logistic regression analysis showed that the use of NSAIDs, active ulcer, Hp infection and ulcer diameter ≥2 cm were risk factors for bleeding in elderly patients with PUD (P<0.05). The Hp positive rate in Forrest I patients was significantly higher than that in Forrest II and Forrest III patients (P<0.05). The positive rate of Hp in Forrest II patients was significantly higher than that in Forrest III patients. Pearson correlation analysis showed that Hp infection was positively correlated with the severity of peptic ulcer bleeding in the elderly (r=0.512, P<0.05). Conclusion The risk of bleeding from PUD is higher in the elderly, especially in patients with active ulcer, Hp infection and ulcer diameter ≥ 2 cm. In the treatment process of PUD patients, the eradication therapy of Hp should be emphasized, which can reduce the risk of bleeding.
ABSTRACT
Glycosite-specific antibody‒drug conjugatess (gsADCs), harnessing Asn297 N-glycan of IgG Fc as the conjugation site for drug payloads, usually require multi-step glycoengineering with two or more enzymes, which limits the substrate diversification and complicates the preparation process. Herein, we report a series of novel disaccharide-based substrates, which reprogram the IgG glycoengineering to one-step synthesis of gsADCs, catalyzed by an endo-N-acetylglucosaminidase (ENGase) of Endo-S2. IgG glycoengineering via ENGases usually has two steps: deglycosylation by wild-type (WT) ENGases and transglycosylation by mutated ENGases. But in the current method, we have found that disaccharide LacNAc oxazoline can be efficiently assembled onto IgG by WT Endo-S2 without hydrolysis of the product, which enables the one-step glycoengineering directly from native antibodies. Further studies on substrate specificity revealed that this approach has excellent tolerance on various modification of 6-Gal motif of LacNAc. Within 1 h, one-step synthesis of gsADC was achieved using the LacNAc-toxin substrates including structures free of bioorthogonal groups. These gsADCs demonstrated good homogeneity, buffer stability, in vitro and in vivo anti-tumor activity. This work presents a novel strategy using LacNAc-based substrates to reprogram the multi-step IgG glycoengineering to a one-step manner for highly efficient synthesis of gsADCs.
ABSTRACT
Drug-induced nephrotoxicity is very common in both new drug development and clinic practice. Various drugs can induce kidney injuries, including tubulointerstitial, glomerular and renal vascular disease. To investigate the mechanism of drug induced nephrotoxicity is important for risk reduction of new drug development, reasonable drug usage, early discovery and effective prevention/treatment of adverse effects in clinics.