Dawei Yang

Background: Metabolic rewiring influences macrophage functions in tumours. However, metabolic heterogeneity of macrophages in early‐stage lung adenocarcinoma (LUAD) has not been fully understood. Methods: Based on single‐cell transcriptomic analysis on lung tissues from human subsolid pulmonary nodules and from Kras ^G12D and Kras ^G12D Tgfbr2 ^−/− mice, we unveiled alterations of macrophage states in LUAD. We applied cell migration and invasion assays to examine effects of ATP binding cassette subfamily A member 1 (ABCA1) in macrophages on tumour progression. In addition, using coculture system, we explored its role in macrophage polarisation. Results: Major macrophage subsets underwent shifts during tumourigenesis, as alveolar macrophages reduced sharply and their interstitial counterparts increased. Of note, tumour‐associated macrophages (TAMs) are metabolically rewired, with a subset enhancing lipid efflux predominated in both human and murine tumour. It was characterised by high expression of the lipid transporter, ABCA1. Targeting ABCA1 by its inhibitor probucol suppressed TAM capacity to induce tumour cell migration and invasion. In addition, inhibiting ABCA1 was associated with dampened immunosuppression of TAMs by shifting them to a M1‐like phenotype. Conclusions: We uncovered TAM heterogeneity in early‐stage LUAD and proposed ABCA1 as a potential target for metabolic rewiring, which manipulated macrophage polarisation states and its effects on tumour aggressiveness.

Background: Early tumour vascular invasion contributes to cancer progression. Tip cells, a subset of tumour endothelial cells, significantly decline after anti‐angiogenic therapy. However, their behaviour and the roles of their signature genes during early invasion are incompletely understood. Methods: This study employed single‐cell transcriptomic analysis and 10x Genomics Visium spatial transcriptomics on fresh lung tissues from patients with pulmonary nodules and from Kras ^G12D (K) and Kras ^G12D Tgfbr2 ^−/− (KT) mice. The role of plasma vesicle‐associated protein (PLVAP), a tip cell marker, was further examined using survival databases, immunofluorescence, in vitro co‐culture, cell migration, invasion assays and endothelial tube formation. Results: Tip cell proportions were elevated in early‐stage lung adenocarcinoma (LUAD) tissues and KT mice, with evidence suggesting they arise from capillaries type I. PLVAP expression was enriched in tumour endothelial cells, induced by TGFβ1, and negatively correlated with patient prognosis. Functionally, PLVAP promoted endothelial cell invasion, migration and angiogenesis, and regulated tumour cell invasiveness. Intercellular analysis revealed that some tip cells also expressed TGFβ1, which may act on adjacent tumour cells to enhance invasion during early tumour development. Conclusion: Tip cells increased during early LUAD progression and likely evolved from capillaries type I. Their marker PLVAP was associated with poor prognosis and pro‐invasive endothelial behaviour. Tumour‐secreted TGFβ1 upregulated PLVAP in endothelial cells, promoting angiogenesis and tumour invasion. Additionally, tip‐cell‐derived TGFβ1 may further stimulate tumour aggressiveness, highlighting a reciprocal interaction that contributes to early tumour progression. Key points: Tip cells expand during early LUAD progression and likely originate from capillary type I endothelial cells. Tumour‐derived TGFβ1 induces PLVAP expression in endothelial cells, linking tumour signals to vascular activation. PLVAP enhances endothelial cell migration, invasion and angiogenic capacity. Endothelial PLVAP promotes tumour cell invasiveness, revealing a reciprocal endothelial‐tumour interaction that drives early tumour progression.

Purpose To assess the benefits of the traditional Chinese medicine (TCM) Qufenghuoxue formula, on the treatment of chemotherapy-induced peripheral neuropathy (CIPN) in patients with lung cancer receiving paclitaxel (PTX). Methods Patients with CIPN grading 2–3 were randomly assigned to three groups of TCM, vitamin B1, or warm water. The intervention duration consisted of four cycles, 3 weeks each, coinciding with the follow-up period. Primary efficacy endpoint was the proportion of patients achieving CIPN relief, defined by reduction in CIPN severity grade, while secondary endpoint evaluated completion of the recommended PTX dosing. Results TCM significantly reduced grade 2–3 CIPN incidence and increased symptom relief (48.6% vs 12.0% vs 7.5%; P < 0.001) with a shorter median time to recovery compared with vitamin B1 and warm water, respectively. Additionally, it improved scores of the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group–Neurotoxicity subscale (11.5 vs 20.4 vs 22.4), neuropathy pain scale (16.8 vs 27.7 vs 29.2) and quality of life (42.6 vs 36.0 vs 33.6; all P < 0.001) and also showed greater potential of completing the recommended dose level of PTX (83.8% vs 74.6% vs 59.7%; P = 0.0034) compared with vitamin B1 and warm water. With warm water as reference, the hazard ratio of PTX dose reductions/cessation due to CIPN was 0.34 (95% confidence interval [CI]: 0.168–0.67, P = 0.002) for TCM and 0.56 (95% CI: 0.314–1.008; P = 0.053) for vitamin B1. Conclusion Qufenghuoxue formula may be a promising strategy for the treatment of CIPN in patients receiving PTX. Trial Registration Chinese Clinical Trial Registry; No.: ChiCTR2300069949. Registered 30 March 30, 2023, URL: www.chictr.org/cn/.

Deep learning-based medical image processing methods can enhance diagnostic accuracy while significantly accelerating clinical decision workflows. However, in order to learn better visual representations, such approaches usually need substantial amount of expert-annotated data, which are highly costly. To address this issue, we propose a novel approach called Dual-Stream Contrastive Learning with Cross-Scale Token Projection (DCL-CsTP), which aims to enhance visual representations and transferable initializations. Specifically, a latent diffusion model (LDM) is leveraged to generate high-quality synthetic medical images in order to expand the dataset. Then we utilize the proposed dual-stream architecture that consists of a global semantic relations stream and a local detail relations stream to learn discriminative medical image representations from the dataset. Furthermore, a cross-scale token projection is designed to enable the model to capture various scales of focus in medical images. Comprehensive experiments are performed on two downstream tasks: medical image classification and segmentation. For multi-classification of pneumonia, our DCL-CsTP method achieves 95.90% accuracy. For lesions segmentation, our DCL-CsTP method attains 89.73% dice coefficient on the International Skin Imaging Collaboration 2018 (ISIC 2018) dataset and 82.50% dice coefficient on the Kvasir-SEG dataset. The performance superiority of the model pre-trained by DCL-CsTP is conclusively demonstrated through the above experiments on various dataset, which shows that DCL-CsTP can enhance diagnostic precision and alleviate radiologists’ image screening burdens.

Introduction: The current clinical management of pulmonary nodules relies heavily on CT follow‐up, without early intervention. This retrospective study investigated the efficacy of OM‐85, a standardized lysate of human respiratory bacteria, in the treatment of high‐risk pulmonary nodules detected by computed tomography (CT) in patients with chronic bronchitis.Methods: This study included 72 patients (93 enrolled nodules) who underwent treatment with OM‐85 and a matched control group of 90 patients (111 control nodules). The primary endpoint included reduced size of high‐risk ground glass nodules based on thin‐layer CT scans during follow‐up. Flow cytometry, multiplex immunofluorescence (mIF) analysis, and scRNA‐seq data were employed to determine differences in the immune cell subsets between the treatment and control groups.Results: Oral OM‐85 treatment significantly reduced lung nodule diameter (p = 0.031), the risk probability of malignancy (p = 0.003), and the likelihood of clinical disease progression (p = 0.0091). The effects of OM‐85 treatment were more pronounced in older patients (> 65‐year‐old) (p = 0.029) and those with longer follow‐up cycles (> 200 days) (p = 0.011). The peripheral blood samples showed a significantly higher proportion of natural killer (NK) cells in the treatment group. Furthermore, mIF staining of the pulmonary nodules and scRNA‐seq data demonstrated a higher percentage of NK cells in the treatment group compared with the control group (p = 0.0003).Conclusion: OM‐85 reduced the size of high‐risk pulmonary nodules and decreased the risk of malignant probability and disease progression in patients with chronic bronchitis by increasing the proportion of NK cells. Therefore, OM‐85 is a potential drug for the treatment of high‐risk pulmonary nodules in patients with chronic bronchitis.

Introduction: Screening of lung nodules helps on early diagnosis of lung cancer, especially invasive pulmonary adenocarcinoma. Artificial intelligence (AI) has been applied in diagnosis of cancers. We used the AI‐assisted lung nodule diagnostic system in the screening of lung nodules and lung cancer.Case Presentation: A 66‐year‐old male complained of coughs and nodules in the right lung of 3‐year duration. A ground‐glass opacity was found in the right upper lung by routine computed tomography (CT). He had no family history of cancer, genetic diseases, or infectious diseases. AI‐assisted analysis found four nodules, of which one was with the risk of malignancy of 88% (LungRads3), one was with the risk of malignancy of 15% (LungRads2), and the other two were smaller in size and considered benign. The patient underwent a thoracoscopic wedge resection of the right upper lung. The intraoperative frozen section pathology report confirmed invasive pulmonary adenocarcinoma, grade II, and primarily of alveolar and adherent types without metastasis.Conclusion: In summary, AI‐assisted lung nodule diagnostic system is effective in the screening of lung nodules and the differentiation between benign and malignant.

Background: To investigate the impact of latent tuberculosis infection (LTBI) on the prognosis of non-small cell lung cancer (NSCLC) patients treated with anti-PD-1 immunotherapy and to assess the correlation between dynamic alterations in T-SPOT.TB results and prognosis. Methods: This retrospective cohort study analyzed clinical data from 127 patients with NSCLC who received anti-PD-1 therapy and underwent T-SPOT.TB testing at our institution between January 2020 and March 2024. Baseline imbalances between groups were addressed using inverse probability of treatment weighting (IPTW). Restricted cubic spline (RCS) modeling, Cox regression and other analyses were conducted both before and after IPTW. Results: Among the entire cohort, 50 patients were in the LTBI group and 77 in the Normal group. No significant differences were observed in mPFS or mOS between the two groups. RCS analysis revealed a nonlinear (U-shaped) relationship between pre-TSPOT values and OS. Patients with a T-SPOT positive (but value ⩽18) exhibited longer OS compared with the other two groups (HR = 0.13, 95% CI [0.03 ~ 0.54], P = .005; after IPTW HR = 0.21, 95% CI [0.05-0.90], P = .035). Among 63 patients monitored for dynamic TSPOT changes, 35 (55.56%) remained persistently negative, 15 (23.81%) remained persistently positive, 2 (3.17%) converted from negative to positive, and 11 (17.46%) converted from positive to negative. No significant differences in ORR, PFS, or OS across these groups. Conclusions: Although no statistically significant differences in treatment efficacy and prognosis were observed between the LTBI and Normal groups, this finding should not be interpreted as therapeutic equivalence, particularly given the limited sample size. Pre-treatment T-SPOT values showed a nonlinear (U-shaped) relationship with patient prognosis (OS). Lower pre-treatment T-SPOT value were associated with longer OS. The dynamic changes in T-SPOT during treatment were not significantly associated with outcomes. Four patients developed active tuberculosis during immunotherapy, with heterogeneous T-SPOT patterns, underscoring the need for TB monitoring in ICI-treated patients.