Background: The chemokine signaling pathway plays an essential role in the development, progression, and immune surveillance of lung squamous cell carcinoma (LUSC). Our study aimed to systematically analyze chemokine signaling-related genes (CSRGs) in LUSC patients with stage I–III disease and develop a prediction model to predict the prognosis and therapeutic response.Methods: A total of 610 LUSC patients with stage I–III disease from three independent cohorts were included in our study. Least absolute shrinkage and selection operator (LASSO) and stepwise multivariate Cox regression analyses were used to develop a CSRG-related signature. GSVA and GSEA were performed to identify potential biological pathways. The ESTIMATE algorithm, ssGSEA method, and CIBERSORT analyses were applied to explore the correlation between the CSRG signature and the tumor immune microenvironment. The TCIA database and pRRophetic algorithm were utilized to predict responses to immunochemotherapy and targeted therapy.Results: A signature based on three CSRGs (CCL15, CXCL7, and VAV2) was developed in the TCGA training set and validated in the TCGA testing set and GEO external validation sets. A Kaplan–Meier survival analysis revealed that patients in the high-risk group had significantly shorter survival than those in the low-risk group. A nomogram combined with clinical parameters was established for clinical OS prediction. The calibration and DCA curves confirmed that the prognostic nomogram had good discrimination and accuracy. An immune cell landscape analysis demonstrated that immune score and immune-related functions were abundant in the high-risk group. Interestingly, the proportion of CD8 T-cells was higher in the low-risk group than in the high-risk group. Immunotherapy response prediction indicated that patients in the high-risk group had a better response to CTLA-4 inhibitors. We also found that patients in the low-risk group were more sensitive to first-line chemotherapeutic treatment and EGFR tyrosine kinase inhibitors. In addition, the expression of genes in the CSRG signature was validated by qRT‒PCR in clinical tumor specimens.Conclusion: In the present study, we developed a CSRG-related signature that could predict the prognosis and sensitivity to immunochemotherapy and targeted therapy in LUSC patients with stage I–III disease. Our study provides an insight into the multifaceted role of the chemokine signaling pathway in LUSC and may help clinicians implement optimal individualized treatment for patients.

Objective To evaluate the effects of doxofylline on inflammatory responses and oxidative stress during mechanical ventilation in rats with chronic obstructive pulmonary disease (COPD). Methods Eight-week-old male Sprague Dawley rats were selected, and the COPD rat model was constructed. The rats were randomly divided into a model group (group M), a model + normal saline group (group N), a doxofylline group (group D), and a control group fed with conventional chow and given normal oxygen supply (group C) (n = 12 in each group). Tracheal intubation and mechanical ventilation were conducted in the rats in each group after anesthesia. A real-time intravenous infusion with 50 mg/kg of doxofylline was conducted in group D, and there was no drug intervention in groups C, N and M. Pathological manifestations of the pulmonary tissues were observed and compared among the groups. And some indicators were evaluated. Results (1) The pulmonary tissues of the rats in groups M, N, and D exhibited typical pathological histological changes of COPD. (2) Groups M, N, and D showed increased Ppeak, PaCO2, total white blood cell count in BALF, and IL-8, TNF-α, and MDA levels in the pulmonary tissue and BALF, and decreased PaO2 and IL-10 and SOD levels, compared with group C. (3). Group D showed decreased Ppeak, PaCO2, total white blood cell count in BALF, and IL-8, TNF-α, and MDA levels in the pulmonary tissue, and increased PaO2 and IL-10 and SOD levels, compared with group N or M. Conclusion Doxofylline was shown to improve ventilation and air exchange during mechanical ventilation in rats with COPD, reduce the inflammatory response and oxidative stress, and mitigate the degree of pulmonary tissue injury.

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Objective: This study evaluated the effect of doxofylline combined with penehyclidine hydrochloride on the pulmonary inflammatory response during mechanical ventilation in chronic obstructive pulmonary disease (COPD), as well as to identify the effects of JNK/SAPK signaling pathway in this inflammatory response. Methods: The COPD model can be constructed by exposing it to cigarette smoke and injections of lipopolysaccharide into the airway. Rats were selected randomly for treatment with doxofylline, penehyclidine hydrochloride, a combination of these two drugs. The control Group received no drug treatment. The date were processed using ANOVA statistical analysis. Results: In all rats, the lung tissue was pathologically characteristic of COPD. Peak airway pressure, the wet/dry weight of lungs, and degrees of TNF-α, IL-10, malondialdehyde, JNK, and p-JNK decreased; while IL-10 and superoxide dismutase levels increased (p < 0.05) in all Groups having received drug treatment (p < 0.05) when compared to control. The combination of penehyclidine hydrochloride with doxofylline had a stronger effect on all of these metrics than either drug alone (p < 0.05). Conclusion: Based on health informatics, This study suggests that the combination of penehyclidine hydrochloride with doxofylline can promote the recovery and maintenance of immune homeostasis in mechanically ventilated COPD rats, and that the underlying mechanism may be is influenced by downregulation of the JNK/SAPK signaling pathway.