11/24/2023 0 Comments Wen jing li![]() In recent years, more and more attention is paid to intraoperative mechanical ventilation strategies, which may affect PPCs in addition to the preoperative optimization of patients’ status and operation style. Considering that approximately 234 million patients worldwide require surgical treatment under general anesthesia each year, reducing the incidence of PPCs may have a great impact on global mobility and mortality. According to the type of surgery and the definition of PPCs, the incidence of PPCs has been reported to range from 5 to 33%. It is quite certain that postoperative pulmonary complications (PPCs) result in more morbidity and mortality, as well as prolong hospital stays. Secondary endpoints will be serum IL-6, TNF-α, procalcitonin (PCT) kinetics during and after surgery, incidence of PPCs, organ dysfunction, length of in-hospital stay, and hospital expense. ![]() Primary endpoints will be postoperative atelectasis measured by chest electrical impedance tomography (EIT) and intraoperative oxygen index. Standard lung-protective ventilation methods such as low tidal volumes (7 ml/kg, predicted body weight, PBW), a fraction of inspired oxygen ≥ 0.5, and recruitment maneuvers (RM) will be applied during and after operation in both groups. ![]() A PEEP of 5 cmH 2O will be used in PEEP5 group, whereas an individualized PEEP value determined by a Cstat-directed PEEP titration procedure will be applied in the iPEEP group. They will be randomly assigned to control group (PEEP5 group) and iPEEP group. A total number of 80 obese patients with body mass index ≥ 32.5 kg/m 2 scheduled for laparoscopic gastric volume reduction and at medium to high risk for PPCs will be enrolled. This study is a single-center, two-arm, prospective, randomized control trial. The Creative Commons Public Domain Dedication waiver ( ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. HER2 MMAE affibody antibody drug conjugates (ADCs).Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. In the future, the design of better strategies that can prolong half-life without affecting cytotoxicity may be useful for further improving the therapeutic potential of these molecules. These results may indicate that prolonging the half-life is very helpful in improving the therapeutic capacity of miniaturized ADCs. The combined effect leads to HP10KM having the most ideal tumor therapeutic ability at the same dosages in the animal model, and its off-target toxicity was also reduced by more than 4 times compared with that of HM. Compared with the conjugate Z HER2-SMCC-MMAE (HM), which has no PEG insertion, Z HER2-PEG4K-MMAE (HP4KM) and Z HER2-PEG10K-MMAE (HP10KM) with 4 or 10 kDa PEG insertions have 2.5- and 11.2-fold half-life extensions and 4.5- and 22-fold in vitro cytotoxicity reductions, respectively. The results showed that the inserted PEG chains significantly prolonged the circulation half-life but also obviously reduced the cytotoxicity of the conjugates. In this study, we propose a novel design strategy for miniaturized ADCs in which drug molecules and small ligand proteins are site-specifically coupled via a bifunctional poly(ethylene glycol) (PEG) chain. ![]() ![]() Miniaturized ADCs may be a potential solution, although their short circulation half-life may lead to new problems. However, traditional ADCs have some limitations, such as reduced permeability in solid tumors due to the high molecular weight of monoclonal antibodies, difficulty in preparation and heterogeneity of products due to the high drug/antibody ratio (4-8 small molecules per antibody). Antibody drug conjugates (ADCs) have become an important modality of clinical cancer treatment. ![]()
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