ABSTRACT
Epigenetic pathways play a critical role in the initiation, progression, and metastasis of cancer. Over the past few decades, significant progress has been made in the development of targeted epigenetic modulators (e.g., inhibitors). However, epigenetic inhibitors have faced multiple challenges, including limited clinical efficacy, toxicities, lack of subtype selectivity, and drug resistance. As a result, the design of new epigenetic modulators (e.g., degraders) such as PROTACs, molecular glue, and hydrophobic tagging (HyT) degraders has garnered significant attention from both academia and pharmaceutical industry, and numerous epigenetic degraders have been discovered in the past decade. In this review, we aim to provide an in-depth illustration of new degrading strategies (2017-2023) targeting epigenetic proteins for cancer therapy, focusing on the rational design, pharmacodynamics, pharmacokinetics, clinical status, and crystal structure information of these degraders. Importantly, we also provide deep insights into the potential challenges and corresponding remedies of this approach to drug design and development. Overall, we hope this review will offer a better mechanistic understanding and serve as a useful guide for the development of emerging epigenetic-targeting degraders.
ABSTRACT
Objective:To compare the use of continuous constant negative pressure drainage and intermittent suction mode drainage in abdominal wall angioplasty to minimize the impact of complications.Methods:From May 2017 to August 2019, the Department of Medical Cosmetology and Plastic Surgery, Wuhan Third Hospital treated 76 female patients after expanded flap repair, aged 27-35 years, with an average age of 30.5±14.2 years, and 58 female patients after abdominal wall plasty, aged 38-55 years, with an average age of 47.8±7.8 years. They were divided into intermittent negative pressure drainage group and continuous negative pressure drainage group. The negative pressure values in different intervals were set according to the type of operation. The drainage volume, drainage time, incidence of hematoma, subcutaneous effusion, flap necrosis rate, primary wound healing rate and drainage related bleeding were recorded and compared between the two groups.Results:After expanded flap repair in 38 cases, flap necrosis occurred in 1 case and hematoma in 3 cases; After abdominal wall plasty in 29 cases, flap necrosis occurred in 0 cases and hematoma in 1 case. The primary healing of incision was higher ( P<0.05), the drainage volume was larger, but the drainage time was shorter ( P<0.05), and no bleeding related to drainage was observed. The effect of monitoring drainage was positively correlated with the effect of operation. Conclusions:Continuous and constant negative pressure drainage is related to the prognosis of patients undergoing expansion flap repair and abdominal wall plasty. It is helpful to improve the effect of plastic surgery and the quality of nursing work. It is an effective method for nursing management after plastic surgery.
ABSTRACT
Objective To investigate the etiology of chronic renal failure (CRF) in middle-aged and elderly people, and to analyze related factors influencing the prognosis. Methods The clinical data of 456 middle-aged and elderly CRF patients treated in our hospital from January 2018 to January 2021 were collected. The etiology and related factors affecting prognosis were analyzed. Results The etiology of 456 middle-aged and elderly patients with CRF was as follows: 220 cases of primary glomerulonephritis (48.24%), 78 cases of diabetic nephropathy (17.14%), 65 cases of hypertensive nephropathy (14.25%), and 37 cases of pyelonephritis (8.11%), 19 cases of drug-induced renal injury (4.16%), 18 cases of obstructive nephropathy (3.95%), 12 cases of lupus nephritis (2.63%), and 7 cases of polycystic kidney disease (1.54%). The age of onset in patients with primary glomerulonephritis and lupus nephritis was lower than that in patients with other causes (P<0.05). The results showed that 94 of the 456 patients died in the hospital, and the mortality rate was 20.6%. Multivariate logistic regression analysis showed that age, severe infection, cerebrovascular disease, arrhythmia, hypertension stage III, left ventricular hypertrophy, and myocardial infarction were high-risk factors leading to poor prognosis (P<0.05). Conclusion The main causes of CRF in middle-aged and elderly patients are primary glomerulonephritis, diabetic nephropathy, and hypertensive nephropathy. Heart disease is the main factor leading to the poor prognosis of such patients. Efforts shall be put into disease prevention and control work for high-risk groups, so as to reduce the incidence and mortality of CRF.