Heterogeneity of immune cells and their communications unveiled by transcriptome profiling in acute inflammatory lung injury.

Background: Acute Respiratory Distress Syndrome (ARDS) or its earlier stage Acute lung injury (ALI), is a worldwide health concern that jeopardizes human well-being. Currently, the treatment strategies to mitigate the incidence and mortality of ARDS are severely restricted. This limitation can be attributed, at least in part, to the substantial variations in immunity observed in individuals with this syndrome. Methods: Bulk and single cell RNA sequencing from ALI mice and single cell RNA sequencing from ARDS patients were analyzed. We utilized the Seurat program package in R and cellmarker 2.0 to cluster and annotate the data. The differential, enrichment, protein interaction, and cell-cell communication analysis were conducted. Results: The mice with ALI caused by pulmonary and extrapulmonary factors demonstrated differential expression including Clec4e, Retnlg, S100a9, Coro1a, and Lars2. We have determined that inflammatory factors have a greater significance in extrapulmonary ALI, while multiple pathways collaborate in the development of pulmonary ALI. Clustering analysis revealed significant heterogeneity in the relative abundance of immune cells in different ALI models. The autocrine action of neutrophils plays a crucial role in pulmonary ALI. Additionally, there was a significant increase in signaling intensity between B cells and M1 macrophages, NKT cells and M1 macrophages in extrapulmonary ALI. The CXCL, CSF3 and MIF, TGFß signaling pathways play a vital role in pulmonary and extrapulmonary ALI, respectively. Moreover, the analysis of human single-cell revealed DCs signaling to monocytes and neutrophils in COVID-19-associated ARDS is stronger compared to sepsis-related ARDS. In sepsis-related ARDS, CD8+ T and Th cells exhibit more prominent signaling to B-cell nucleated DCs. Meanwhile, both MIF and CXCL signaling pathways are specific to sepsis-related ARDS. Conclusion: This study has identified specific gene signatures and signaling pathways in animal models and human samples that facilitate the interaction between immune cells, which could be targeted therapeutically in ARDS patients of various etiologies.

Phase II trial of recombinant human endostatin in combination with concurrent chemoradiotherapy in patients with stage III non-small-cell lung cancer.

PURPOSE: The objective of this study was to evaluate the efficacy and safety of Endostar combined with concurrent chemoradiotherapy (CCRT) in patients with stage III non-small-cell lung cancer (NSCLC). METHODS: Patients with unresectable stage III NSCLC were treated with Endostar (7.5mg/m(2)/d) for 7days at weeks 1, 3, 5, and 7, while two cycles of docetaxel (65mg/m(2)) and cisplatin (65mg/m(2)) were administered on days 8 and 36, with concurrent thoracic radiation to a dose of 60-66Gy. Primary end points were short-term efficacy and treatment-related toxicity. RESULTS: Fifty patients were enrolled into the study, and 48 were assessable. Of the 48 patients, 83% had stage IIIB and 65% had N3 disease. Median follow-up was 25.0months. Overall response rate was 77%. The estimated median progression-free survival (PFS) was 9.9months, and the estimated median overall survival (OS) was 24.0months. The 1-, 2-, and 3-year local control rates were 75%, 67%, and 51%, PFS rates were 48%, 27%, and 16%, and OS rates were 81%, 50%, and 30%, respectively. All toxicities were tolerable with proper treatment. CONCLUSIONS: The combination of Endostar with CCRT for locally advanced NSCLC patients was feasible and showed promising survival and local control rates.

Involved-field radiotherapy versus elective nodal irradiation in combination with concurrent chemotherapy for locally advanced non-small cell lung cancer: a prospective randomized study.

This prospective randomized study is to evaluate the locoregional failure and its impact on survival by comparing involved field radiotherapy (IFRT) with elective nodal irradiation (ENI) in combination with concurrent chemotherapy for locally advanced non-small cell lung cancer. It appears that higher dose could be delivered in IFRT arm than that in ENI arm, and IFRT did not increase the risk of initially uninvolved or isolated nodal failures. Both a tendency of improved locoregional progression-free survival and a significant increased overall survival rate are in favor of IFRT arm in this study.

[Impact of changing gross tumor volume delineation of intensity-modulated radiotherapy on the dose distribution and clinical treatment outcome after induction chemotherapy for the primary locoregionally advanced nasopharyngeal carcinoma].

BACKGROUND AND OBJECTIVE: The gross tumor volume (GTV) obviously reduces after induction chemotherapy (IC) for primary locoregionally advanced nasopharyngeal carcinoma (NPC). This study was to investigate the impact of changing gross tumor volume delineation on the dose distribution and clinical treatment outcome after IC. METHODS: From January 2008 to April 2009, 24 patients with Stage III-IVb primary locoregionally advanced NPC were treated with TPF regimen IC followed by intensity-modulated radiotherapy (IMRT) with concurrent chemotherapy . The primary GTVs were delineated into two parts: the post-IC primary GTV (GTVpost-IC-NP), and the region of pre-IC primary GTV minus GTVpost-IC-NP (GTVpre-post-IC-NP). The dose distributions of two plans with GTVpost-IC-NP or pre-IC primary GTV were assessed by analyzing ten cases. The clinical treatment outcome and toxicity of all patients were observed. RESULTS: The post-IC GTV was significantly smaller than the pre-IC GTV (primary GTV 25.5 cm3 vs. 51.1 cm(3),P=0.001; lymph nodes GTV 9.1 cm(3) vs. 31.4 cm(3), P=0.035; primary + lymph nodes GTV 33.2 cm(3) vs. 82.6 cm(3),P=0.004), the overall GTV with an average shrinkage of 61%. The high dose region was also smaller after IC (volumes covered by 64.4 Gy were 422.9 cm3 vs. 457.9 cm3, P=0.003; 274.2 cm(3) vs.334.5 cm(3) by 68 Gy, P=0.041). The complete response rate was 38% after IC, and 100% three month after radiotherapy. The toxicity of following IMRT with concurrent chemotherapy was similar to that of IMRT with concurrent chemotherapy alone. With median follow-up of 9 months, the locoregionally control rate was 100% and only one patient presented metastasis 15 months after treatment. CONCLUSIONS: TPF regimen IC could significantly reduce tumor volume. The following IMRT with GTVpost-IC-NP plan reduced the high dose region, which didn't add toxicity while had excellent short-term treatment outcome.