Enhanced Hybrid Ant Colony Optimization for Machining Line Balancing Problem with Compound and Complex Constraints

Targeted at the machining production line balancing problem, based on the precedence constraint relation of the present machining task, this article suggests adding practical constraints such as advanced station preparations, post-auxiliary tasks, and tool changing. The study introduced ‘tight’ and ’or’ constraints to bring the problem definition closer to the actual situation. For this problem, a mixed-integer programming model was constructed in this study. The model redefines the machining and auxiliary processing tasks and adds new time constraints to the station. The model considers two optimisation objectives: the number of stations and the machining line balancing rate. In view of the complexity of the problem, heuristic task set filtering mechanisms were designed and added to the ant colony optimisation, to satisfy the above compound and complex constraints. The processing task chain was constructed using the rules of ant colony pheromone accumulation and a random search mechanism. The study designed a Gantt chart generation module to improve the usability and visibility of the program. Ultimately, through an actual case study of a complex box part including 73 processing elements and realising the design and planning of machining production lines that meet complex constraints by substituting algorithms, the balance rates of several groups of optimisation schemes were higher than 90%, which showed that the algorithm is effective and has a good economy and practicability

The activity and immune dynamics of PD-1 inhibition on high-risk pulmonary ground glass opacity lesions: insights from a single-arm, phase II trial

Abstract Immune checkpoint inhibitors targeting the programmed cell death-1 (PD-1) protein significantly improve survival in patients with advanced non-small-cell lung cancer (NSCLC), but its impact on early-stage ground-glass opacity (GGO) lesions remains unclear. This is a single-arm, phase II trial (NCT04026841) using Simon’s optimal two-stage design, of which 4 doses of sintilimab (200 mg per 3 weeks) were administrated in 36 enrolled multiple primary lung cancer (MPLC) patients with persistent high-risk (Lung-RADS category 4 or had progressed within 6 months) GGOs. The primary endpoint was objective response rate (ORR). T/B/NK-cell subpopulations, TCR-seq, cytokines, exosomal RNA, and multiplexed immunohistochemistry (mIHC) were monitored and compared between responders and non-responders. Finally, two intent-to-treat (ITT) lesions (pure-GGO or GGO-predominant) showed responses (ORR: 5.6%, 2/36), and no patients had progressive disease (PD). No grade 3–5 TRAEs occurred. The total response rate considering two ITT lesions and three non-intent-to-treat (NITT) lesions (pure-solid or solid-predominant) was 13.9% (5/36). The proportion of CD8+ T cells, the ratio of CD8+/CD4+, and the TCR clonality value were significantly higher in the peripheral blood of responders before treatment and decreased over time. Correspondingly, the mIHC analysis showed more CD8+ T cells infiltrated in responders. Besides, responders’ cytokine concentrations of EGF and CTLA-4 increased during treatment. The exosomal expression of fatty acid metabolism and oxidative phosphorylation gene signatures were down-regulated among responders. Collectively, PD-1 inhibitor showed certain activity on high-risk pulmonary GGO lesions without safety concerns. Such effects were associated with specific T-cell re-distribution, EGF/CTLA-4 cytokine compensation, and regulation of metabolism pathways