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ObjectivesTo evaluate the effects of platinum-based neoadjuvant chemotherapy (NACT) on the STING/IFN pathway and tumor-infiltrating lymphocytes (TILs) in non-small cell lung cancer (NSCLC), as well as clinicopathological factors affecting patient survival.Materials and methodsA total of 68 patients aged 34-77 years with NSCLC who received neoadjuvant chemotherapy and surgical treatment from March 2012 to February 2019 were reviewed, and the clinical pathological data and paired tissue specimens before and after NACT were collected. Immunohistochemistry and immunofluorescence were used to detect the protein levels of STING, PD-L1 and IFN-β, and the infiltration density of CD3+ TILs and CD8+TILs. The correlation between the expression of STING, PD-L1, IFN-β and the infiltration density of CD3+ TILs and CD8+ TILs as well as the clinicopathological characteristics before and after NACT was analyzed. The relationship between the related indexes, clinicopathological features and prognosis was also discussed.ResultsNACT increased the expression of STING, IFN-β and PD-L1 in tumor cells, and the infiltration of CD3+ and CD8+ TILs. In addition, ypTNM stage, ypN stage, changes in CD3+ TILs and in PD-L1 were associated with DFS (disease-free survival). CD3+ TILs changes and ypN stage were associated with OS (overall survival). Notably, ypN stage and CD3+ TILs changes were independent prognostic factors for DFS and OS.ConclusionNACT stimulates STING/IFN-β pathway, promotes infiltration of CD3+ and CD8+ TILs, triggers innate and adaptive immunity, and also upregulates PD-L1, which complemented the rationale for neoadjuvant chemotherapy in combination with immunotherapy. In addition, DFS was longer in patients with ypTNM I, ypN0-1, and elevated CD3+TILs after NACT. Patients with ypN0 and elevated CD3+ TILs after NACT had better OS benefits.

Abstract Background Attributed to the immunosuppression caused by malignancy itself and its treatments, cancer patients are vulnerable to developing nosocomial infections. This study aimed to develop a nomogram to predict the in-hospital death risk of these patients. Methods This retrospective study was conducted at a medical center in Northwestern China. The univariate and multivariate logistic regression analyses were adopted to identify predictive factors for in-hospital mortality of nosocomial infections in cancer patients. A nomogram was developed to predict the in-hospital mortality of each patient, with receiver operating characteristic curves and calibration curves being generated to assess its predictive ability. Furthermore, decision curve analysis (DCA) was also performed to estimate the clinical utility of the nomogram. Results A total of 1,008 nosocomial infection episodes were recognized from 14,695 cancer patients. Extended-spectrum β-lactamase (ESBL)-producing Escherichia coli (15.5%) was the most predominant causative pathogen. Besides, multidrug-resistant strains were discovered in 25.5% of cases. The multivariate analysis indicated that Eastern Cooperative Oncology Group Performance Status 3–4, mechanical ventilation, septic shock, hypoproteinemia, and length of antimicrobial treatment

Idiopathic pulmonary fibrosis (IPF) is a devastating interstitial lung disease with a bleak prognosis. Mounting evidence suggests that IPF shares bio-molecular similarities with lung cancer. Given the deep understanding of the programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway in cancer immunity and the successful application of immune checkpoint inhibitors (ICIs) in lung cancer, recent studies have noticed the role of the PD-1/PD-L1 axis in IPF. However, the conclusions are ambiguous, and the latent mechanisms remain unclear. In this review, we will summarize the role of the PD-1/PD-L1 axis in IPF based on current murine models and clinical studies. We found that the PD-1/PD-L1 pathway plays a more predominant profibrotic role than its immunomodulatory role in IPF by interacting with multiple cell types and pathways. Most preclinical studies also indicated that blockade of the PD-1/PD-L1 pathway could attenuate the severity of pulmonary fibrosis in mice models. This review will bring significant insights into understanding the role of the PD-1/PD-L1 pathway in IPF and identifying new therapeutic targets.

Cancer cells reprogram their metabolism to meet their growing demand for bioenergy and biosynthesis. The metabolic profile of cancer cells usually includes dysregulation of main nutritional metabolic pathways and the production of metabolites, which leads to a tumor microenvironment (TME) having the characteristics of acidity, hypoxic, and/or nutrient depletion. Therapies targeting metabolism have become an active and revolutionary research topic for anti-cancer drug development. The differential metabolic vulnerabilities between tumor cells and other cells within TME provide nanotechnology a therapeutic window of anti-cancer. In this review, we present the metabolic characteristics of intrinsic cancer cells and TME and summarize representative strategies of nanoparticles in metabolism-regulating anti-cancer therapy. Then, we put forward the challenges and opportunities of using nanoparticles in this emerging field.

BackgroundReports of the clinical outcomes associated with the co-occurrence of atrial cardiomyopathy (ACM) and lung cancer (LC) are limited.ObjectivesThis study aims to investigate the influence of ACM on the prognosis of LC patients and related clinical determinants.MethodsNewly diagnosed LC patients from January 1st, 2015, to December 31st, 2020, were retrospectively enrolled at the First Affiliated Hospital of Xi’an Jiaotong University. The demographics and overall survival (OS) of the patients with or without ACM were compared. The survival rate was analyzed using the Kaplan–Meier method and multivariate Cox regression analysis. Binary logistic regression analysis was used to determine the risk factors for ACM.ResultsA total of 306 patients (65.04 ± 10.30 years of age, 72.88% male) were analyzed. The prevalence of ACM in the non-small cell lung cancer (241, 78.76%) and small cell lung cancer (65, 21.24%) population was not statistically different. Overall, 53 (17.32%) LC patients had coexisting ACM. ACM patients were older (69 vs. 64, p = 0.0013) and had higher D-dimer levels (1.0 vs. 0.6, p = 0.001), lower serum calcium levels (2.23 vs. 2.31, p = 0.001), lower left ventricular ejection fraction (LVEF) values (67% vs. 69%, p = 0.036) and had more frequent coronary comorbidity disease (16.98% vs. 8.82%, p = 0.031). The median OS for patients with or without ACM was 15 months and 25 months, respectively (p = 0.018). Coexisting ACM compared to non-ACM was associated with worse OS in patients with LC (HR = 1.543, 95% CI: 1.042–2.283, p = 0.030).ConclusionCoexisting ACM is associated with undesirable survival outcomes in patients with LC. These findings could help us to better understand the cardiac burden in these patients and provide additional risk stratification for them.

Introduction Combined small cell lung cancer (C-SCLC) represents a rare subtype of all small cell lung cancer cases, with limited studies investigated its prognostic factors. The aim of this study was to construct a novel nomogram to predict the overall survival (OS) of patients with C-SCLC. Methods In this retrospective study, a total of 588 C-SCLC patients were selected from the Surveillance, Epidemiology, and End Results database. The univariate and multivariate Cox analyses were performed to identify optimal prognostic variables and construct the nomogram, with concordance index (C-index), receiver operating characteristic curves, and calibration curves being used to evaluate its discrimination and calibration abilities. Furthermore, decision curve analysis (DCA), integrated discrimination improvement (IDI), and net reclassification index (NRI) were also adopted to assess its clinical utility and predictive ability compared with the classic TNM staging system. Results Seven independent predictive factors were identified to construct the nomogram, including T stage, N stage, M stage, brain metastasis, liver metastasis, surgery, and chemotherapy. We observed a higher C-index in both the training (.751) and validation cohorts (.736). The nomogram has higher area under the curve in predicting 6-, 12-, 18-, 24-, and 36-month survival probability of patients with C-SCLC. Meanwhile, the calibration curves also revealed high consistencies between the actual and predicted OS. DCA revealed that the nomogram could provide greater clinical net benefits to these patients. We found that the NRI for 6- and 12-month OS were .196 and .225, and the IDI for 6- and 12-month OS were .217 and .156 in the training group, suggesting that the nomogram can predict a more accurate survival probability. Similar results were also observed in the validation cohort. Conclusion We developed and verified a novel nomogram that can help clinicians recognize high-risk patients with C-SCLC and predict their OS.

The number of patients with oncologic and cardiologic comorbidities is increasing. A growing number of evidence shows an inextricable link between cancer, atrial fibrillation, and atrial cardiomyopathy. Cancer itself and resultant inflammation, anticancer treatment, and other comorbidities lead to atrial remodeling and fibrosis, which increases the tendency to develop atrial cardiomyopathy and atrial fibrillation. The scarcity of current literature and ambiguous results make its relationship difficult to fully understand. In this review, we will summarize existing evidence of the relationships and interactions among cancer, atrial cardiomyopathy, and atrial fibrillation and discuss the underlying mechanisms, and provide better information for the management of these patients.

BackgroundBladder cancer (BLCA) is the 11th most common malignancy worldwide. Although significant improvements have been made in screening, diagnosis, and precise management in recent years, the prognosis of BLCA remains bleak.ObjectivesThis study aimed to investigate the prognostic significance of tumor-infiltrating immune cells and construct ceRNA networks in BLCA patients.MethodsThe expression data of BLCA patients were obtained from The Cancer Genome Atlas (TCGA) database. A competing endogenous RNA (ceRNA) network was constructed to identify the hub genes involved in the prognosis of BLCA. The CIBERSORT algorithm was utilized to investigate the infiltration levels of 22 subsets of immune cells. Ultimately, the nomogram was generated to visualize the survival probability of each patient, with the calibration curve being performed to assess its performance. Furthermore, the Pearson correlation test was used to explore the correlation between the identified hub genes in the ceRNA network and the prognostic-related immune cells.ResultsA total of eight elements in the ceRNA network were considered as key members and correlated with the prognosis of BLCA, including ELN, SREBF1, DSC2, TTLL7, DIP2C, SATB1, hsa-miR-20a-5p, and hsa-miR-29c-3p. T cells CD8, T cells follicular helper (Tfh), and neutrophils were identified as independent prognostic factors in BLCA. The co-expression analysis showed that there was a significant correlation between the identified hub genes and immune cells.ConclusionOur results suggest that the mechanism of hsa-miR-29c-3p regulates the expression of ELN and DSC2, and the infiltration of Tfh and neutrophils might play pivotal roles in the progression of BLCA.