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BackgroundStatic tumor features before initiating anti-tumor treatment were insufficient to distinguish responding from non-responding tumors under the selective pressure of immuno-therapy. Herein we investigated the longitudinal dynamics of peripheral blood inflammatory indexes (dPBI) and its value in predicting major pathological response (MPR) in non-small cell lung cancer (NSCLC).MethodsA total of 147 patients with NSCLC who underwent neoadjuvant immunochemotherapy were retrospectively reviewed as training cohort, and 26 NSCLC patients from a phase II trial were included as validation cohort. Peripheral blood inflammatory indexes were collected at baseline and as posttreatment status; their dynamics were calculated as their posttreatment values minus their baseline level. Least absolute shrinkage and selection operator algorithm was utilized to screen out predictors for MPR, and a MPR score was integrated. We constructed a model incorporating this MPR score and clinical predictors for predicting MPR and evaluated its predictive capacity via the area under the curve (AUC) of the receiver operating characteristic and calibration curves. Furthermore, we sought to interpret this MPR score in the context of micro-RNA transcriptomic analysis in plasma exosomes for 12 paired samples (baseline and posttreatment) obtained from the training cohort.ResultsLongitudinal dynamics of monocyte–lymphocyte ratio, platelet-to-lymphocyte ratio, platelet-to-albumin ratio, and prognostic nutritional index were screened out as significant indicators for MPR and a MPR score was integrated, which was further identified as an independent predictor of MPR. Then, we constructed a predictive model incorporating MPR score, histology, and differentiated degree, which discriminated MPR and non-MPR patients well in both the training and validation cohorts with an AUC value of 0.803 and 0.817, respectively. Furthermore, micro-RNA transcriptomic analysis revealed the association between our MPR score and immune regulation pathways. A significantly better event-free survival was seen in subpopulations with a high MPR score.ConclusionOur findings suggested that dPBI reflected responses to neoadjuvant immuno-chemotherapy for NSCLC. The MPR score, a non-invasive biomarker integrating their dynamics, captured the miRNA transcriptomic pattern in the tumor microenvironment and distinguished MPR from non-MPR for neoadjuvant immunochemotherapy, which could support the clinical decisions on the utilization of immune checkpoint inhibitor-based treatments in NSCLC patients.

In this paper, a novel dual-three-phase dual-rotor flux-switching permanent magnet (PM) (DRFSPM) machine, building upon conventional FSPM machines, is proposed, where the stator is equipped with dual PMs and dual armature windings, enabling it to operate in various working modes and provide fault tolerance in the event of PM or armature winding faults. Depending on the magnetization directions of the PMs, the proposed DRFSPM machine’s structure can be categorized as 6N-DRFSPM or NS-DRFSPM. In order to assess the electromagnetic performance of the proposed DRFSPM machines with two different magnetizing modes, the topology and operating principle of the two DRFSPM machines are introduced first. Then, the no-load air-gap flux density of the two proposed machines is investigated for a more optimized and purposeful design. Finally, a comparison of the electromagnetic performance between the two proposed DRFSPM machines is conducted by finite-element analysis (FEA), and the FEA-predicted results indicate that the proposed 6N-DRFSPM machine outperforms the NS-DRFSPM machine, as it exhibits a larger back-EMF and average torque and a smaller cogging torque and torque ripple.