ABSTRACT
In this study, an ultra-high-precision pneumatic force servo system (UPFSS) is proposed. On the one hand, a novel air-floating pneumatic cylinder (AFPC) with an air-floating piston capable of independent air supply and exhaust is developed for this system, and its special flow channel design allows the air-floating piston to be suspended in the cylinder without being constrained by the pressure in the chambers. The friction force of the AFPC is less than 0.0049 N. On the other hand, a leakage chamber is constructed to simulate the clearance between the air-floating piston and the cylinder wall, and a fuzzy proportional integral (FPI)-based pressure control system (PCS) is designed for the simulated leakage chamber. Furthermore, a novel particle swarm optimization algorithm integrating Gaussian mutation and fuzzy theory (IGF-PSO) is presented. After testing, the IGF-PSO algorithm is found to have outstanding optimization performance. Then, the parameters of the FPI controller are optimized through the IGFPSO algorithm. Experimental comparisons reveal that the steady-state error achieved by the parameter-optimized pressure controller in response to the leakage condition is about 38 % smaller than that achieved by the pressure controller with parameters obtained using the trial-and-error method. Finally, the UPFSS is tested by using the optimized PCS to supply compressed air to the chamber of the AFPC. The results show that the UPFSS achieves a steady-state error of no more than 0.0279 N in the continuous step response within the range of 240 N.
ABSTRACT
Background: Previous clinical randomized controlled trials (RCTs) have demonstrated that immune checkpoint inhibitors (ICIs) cause various toxicities during cancer treatment, but the effects of different inhibitors in combination with chemotherapy for cardiotoxicity remain controversial. The aim of the present study was to assess cardiotoxicity caused by programmed cell death protein 1 (PD-1), programmed cell death-Ligand 1 (PD-L1), and cytotoxic T lymphocyte associate protein-4 (CTLA-4) in combination with chemotherapy to treat lung cancer. Methods: The following ICIs were included in the present study: durvalumab, avelumab, ipilimumab, atezolizumab, pembrolizumab, cemiplimab, and nivolumab. The relevant information was extracted using a predefined data extraction table, and the risk of bias was assessed in randomized controlled trials using the Cochrane Bias Risk tool. The main outcomes were hypertension, heart failure, pericardial effusion, and other adverse cardiac events. The random effects model was used to conduct a paired meta-analysis, and a random effects network meta-analysis was then performed within a Bayesian framework. Results: In total, 17 RCTs were included in the present study. There were 11,063 individuals in the experimental and control groups, with an average age greater than 60 years. Based on the evaluation of all drug classes in RCTs, CTLA-4+chemotherapy (RR, -0.69 [95% CI, 2.91-1.52] and PD-L1 (RR, -0.21 [95% CI, -1.03-0.60]) were less cardiotoxic than the control arm, which indicated they were safer options for adverse cardiac events. PD-L1 alone was less cardiotoxic than PD-1 alone (RR, -0.57 [95% CI, -1.96-0.82]). Further, the dual immunotarget inhibitor, PD-1+CTLA-4, had the lowest SUCRA value and had the highest cardiotoxicity (SUCRA=9). Conclusion: When classified according to drug type, CTLA-4+chemotherapy is associated with fewer cardiac adverse events compared to other treatments. Dual immunotarget inhibitors are more likely to have adverse cardiac reactions. Therefore, clinicians should consider this evidence when developing an ICI immunotherapy regimen for lung cancer. Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier CRD42023360931.
ABSTRACT
BACKGROUND: The resistance to epidermal growth factor receptor (EGFR)- tyrosine kinase inhibitors (TKIs) therapy is currently the major clinical challenge in the treatment of lung cancer. This study aims to reveal the role of glucagon-like peptide (GLP) 2 and GLP-2 receptor (GLP2R) signaling on the EGFR-TKIs and cisplatin resistance of lung cancer cells. METHODS: The common differentially expressed genes in PC9 and HCC827 cells that were individually resistant to one of the three EGFR-TKIs (dacomitinib, osimertinib and afatinib) were screened. The data were from GSE168043 and GSE163913. The expression of GLP2R in drug-resistant cells was detected by western blot. The effect of GLP2R expression down- or up-regulation on resistance to dacomitinib, osimertinib, afatinib or cisplatin was measured by CCK-8 and flow cytometry assays. The long-acting analog of GLP-2, teduglutide, treated the parental cells. RESULTS: A total of 143 common differentially expressed genes were identified. Compared with the parent cells, the GLP2R expression in drug-resistant cell lines was significantly up-regulated. The exogenous expression of GLP2R in parental cells enhanced cell viability, while knockdown of GLP2R levels in drug-resistant cell lines inhibited cell viability. In addition, teduglutide treatment also enhanced the viability of lung cancer cells. CONCLUSION: GLP2-GLP2R signal may change the sensitivity of cells to EGFR-TKIs and cisplatin. The development of GLP-2 or GLP2R inhibitors may be beneficial to the clinical treatment of lung cancer.
