PESSA: A web tool for pathway enrichment score-based survival analysis in cancer.

The activation levels of biologically significant gene sets are emerging tumor molecular markers and play an irreplaceable role in the tumor research field; however, web-based tools for prognostic analyses using it as a tumor molecular marker remain scarce. We developed a web-based tool PESSA for survival analysis using gene set activation levels. All data analyses were implemented via R. Activation levels of The Molecular Signatures Database (MSigDB) gene sets were assessed using the single sample gene set enrichment analysis (ssGSEA) method based on data from the Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), The European Genome-phenome Archive (EGA) and supplementary tables of articles. PESSA was used to perform median and optimal cut-off dichotomous grouping of ssGSEA scores for each dataset, relying on the survival and survminer packages for survival analysis and visualisation. PESSA is an open-access web tool for visualizing the results of tumor prognostic analyses using gene set activation levels. A total of 238 datasets from the GEO, TCGA, EGA, and supplementary tables of articles; covering 51 cancer types and 13 survival outcome types; and 13,434 tumor-related gene sets are obtained from MSigDB for pre-grouping. Users can obtain the results, including Kaplan-Meier analyses based on the median and optimal cut-off values and accompanying visualization plots and the Cox regression analyses of dichotomous and continuous variables, by selecting the gene set markers of interest. PESSA (https://smuonco.shinyapps.io/PESSA/ OR http://robinl-lab.com/PESSA) is a large-scale web-based tumor survival analysis tool covering a large amount of data that creatively uses predefined gene set activation levels as molecular markers of tumors.

Efficacy of targeted therapy in patients with non-small cell lung cancer harboring very rare mutations in EGFR exon 18.

Background: Somatic mutations in epidermal growth factor receptor (EGFR) exon 18 are classified as uncommon or rare mutations in non-small cell lung cancer (NSCLC), in this context, other than G719X or E709X exon 18 mutations are even more rare and heterogeneous. In such scenario, first line treatment options are still debated. The aim of this study was to investigate the response of NSCLC patients harboring very rare exon 18 mutations to EGFR tyrosine kinase inhibitors (EGFR-TKIs). Methods: This retrospective descriptive study included 105 patients with NSCLC harboring mutations in EGFR exon 18 diagnosed at West China Hospital. The clinical response to EGFR-TKIs was evaluated according to different classifications of mutations in 45 NSCLC patients: 39 harboring G719X or E709X mutations and 6 harboring very rare mutations in EGFR exon 18. Results: Among 105 patients, 84% (88/105) harbored rare mutations in EGFR exon 18, including G719X and E709X mutations. The remaining 16% (17/105) had very rare mutations in EGFR exon 18, including E709_710delinsX and G724S. For the subsequent efficacy analysis of EGFR-TKI in 45 NSCLC patients, patients harboring very rare mutations achieved a favorable disease control rate (DCR) of 100% and had a median progression-free survival (PFS) of 17.2 months, which was not significantly different compared to patients harboring G719X or E709X (P=0.59). Conclusions: EGFR-TKIs showed great efficacy in terms of responses and survival in patients harboring exon 18 EGFR rare mutations. This may justify the use of targeted therapies as a potential treatment strategy for these patients.

Early detection and prognosis evaluation for hepatocellular carcinoma by circulating tumour DNA methylation: A multicentre cohort study.

BACKGROUND: Early diagnosis of hepatocellular carcinoma (HCC) can significantly improve patient survival. We aimed to develop a blood-based assay to aid in the diagnosis, detection and prognostic evaluation of HCC. METHODS: A three-phase multicentre study was conducted to screen, optimise and validate HCC-specific differentially methylated regions (DMRs) using next-generation sequencing and quantitative methylation-specific PCR (qMSP). RESULTS: Genome-wide methylation profiling was conducted to identify DMRs distinguishing HCC tumours from peritumoural tissues and healthy plasmas. The twenty most effective DMRs were verified and incorporated into a multilocus qMSP assay (HepaAiQ). The HepaAiQ model was trained to separate 293 HCC patients (Barcelona Clinic Liver Cancer (BCLC) stage 0/A, 224) from 266 controls including chronic hepatitis B (CHB) or liver cirrhosis (LC) (CHB/LC, 96), benign hepatic lesions (BHL, 23), and healthy controls (HC, 147). The model achieved an area under the curve (AUC) of 0.944 with a sensitivity of 86.0% in HCC and a specificity of 92.1% in controls. Blind validation of the HepaAiQ model in a cohort of 523 participants resulted in an AUC of 0.940 with a sensitivity of 84.4% in 205 HCC cases (BCLC stage 0/A, 167) and a specificity of 90.3% in 318 controls (CHB/LC, 100; BHL, 102; HC, 116). When evaluated in an independent test set, the HepaAiQ model exhibited a sensitivity of 70.8% in 65 HCC patients at BCLC stage 0/A and a specificity of 89.5% in 124 patients with CHB/LC. Moreover, HepaAiQ model was assessed in paired pre- and postoperative plasma samples from 103 HCC patients and correlated with 2-year patient outcomes. Patients with high postoperative HepaAiQ score showed a higher recurrence risk (Hazard ratio, 3.33, p < .001). CONCLUSIONS: HepaAiQ, a noninvasive qMSP assay, was developed to accurately measure HCC-specific DMRs and shows great potential for the diagnosis, detection and prognosis of HCC, benefiting at-risk populations.

ChatGPT's ability to generate realistic experimental images poses a new challenge to academic integrity.

The rapid advancements in large language models (LLMs) such as ChatGPT have raised concerns about their potential impact on academic integrity. While initial concerns focused on ChatGPT's writing capabilities, recent updates have integrated DALL-E 3's image generation features, extending the risks to visual evidence in biomedical research. Our tests revealed ChatGPT's nearly barrier-free image generation feature can be used to generate experimental result images, such as blood smears, Western Blot, immunofluorescence and so on. Although the current ability of ChatGPT to generate experimental images is limited, the risk of misuse is evident. This development underscores the need for immediate action. We suggest that AI providers restrict the generation of experimental image, develop tools to detect AI-generated images, and consider adding "invisible watermarks" to the generated images. By implementing these measures, we can better ensure the responsible use of AI technology in academic research and maintain the integrity of scientific evidence.

Immune checkpoint inhibitor plus chemotherapy as first-line treatment for non-small cell lung cancer with malignant pleural effusion: a retrospective multicenter study.

BACKGROUND: Immune checkpoint inhibitors (ICI) combined with chemotherapy are efficacious for treating advanced non-small cell lung cancer (NSCLC); however, the effectiveness of this approach in the malignant pleural effusion (MPE) population is unclear. This study evaluated ICI plus chemotherapy in NSCLC patients with MPE. METHODS: Patients from 3 centers in China with NSCLC and MPE who received ICI plus chemotherapy (ICI Plus Chemo) or chemotherapy alone (Chemo) between December 2014 and June 2023 were enrolled. Clinical outcomes and adverse events (AEs) were compared. RESULTS: Of 155 eligible patients, the median age was 61.0 years old. Males and never-smokers accounted for 73.5% and 39.4%, respectively. Fifty-seven and 98 patients received ICI Plus Chemo or Chemo, respectively. With a median study follow-up of 10.8 months, progression-free survival (PFS) was significantly longer with ICI Plus Chemo than with Chemo (median PFS: 7.4 versus 5.7 months; HR = 0.594 [95% CI: 0.403-0.874], P = 0.008). Median overall survival (OS) did not differ between groups (ICI Plus Chemo: 34.2 versus Chemo: 28.3 months; HR = 0.746 [95% CI: 0.420-1.325], P = 0.317). The most common grade 3 or worse AEs included decreased neutrophil count (3 [5.3%] patients in the ICI Plus Chemo group vs. 5 [5.1%] patients in the Chemo group) and decreased hemoglobin (3 [5.3%] versus 10 [10.2%]). CONCLUSIONS: In patients with untreated NSCLC with MPE, ICI plus chemotherapy resulted in significantly longer PFS than chemotherapy and had a manageable tolerability profile, but the effect on OS may be limited.

[Progress on Neoadjuvant Immunotherapy for Resectable Non-small Cell Lung Cancer].

In recent years, there has been a consensus regarding the enhancement of prognosis in patients with advanced non-small cell lung cancer (NSCLC) through the utilization of immune checkpoint inhibitors (ICIs). Numerous clinical studies have also demonstrated the substantial value of immunotherapy for resectable NSCLC patients. Nevertheless, there remain controversies surrounding the exploration of immune combination strategies, treatment-related side effects, prognostic biomarkers, as well as other issues in the neoadjuvant therapy setting. Consequently, this article presents a comprehensive overview of the recent advancements in neoadjuvant immunotherapy for resectable NSCLC, stimulating fresh perspectives and delving into its merits and challenges in clinical application.
.

Development and validation of a deep-learning model for the detection of non-displaced femoral neck fractures with anteroposterior and lateral hip radiographs.

Background: Hip fractures, including femoral neck fractures, are a significant cause of morbidity and mortality in the elderly population and are typically diagnosed using plain radiography. However, diagnosing non-displaced femoral neck fractures can be challenging due to their subtle appearance on hip radiographs. Previous deep-learning models have shown low accuracy in identifying these fractures on anteroposterior (AP) radiographs; however, no studies have used lateral radiographs. This study aimed to evaluate the potential of using deep-learning with both AP and lateral hip radiographs to automatically identify non-displaced femoral neck fractures. Methods: We conducted a retrospective analysis of patients with femoral neck fractures at The First Affiliated Hospital of Xiamen University. All the hip radiographs were reviewed, and cases of non-displaced femoral neck fractures were included in the study. Additionally, 439 participants with normal hip radiographs were also included in the study. A vision transformer (Vit) model was developed using 1,536 AP and lateral hip radiograph. The model's performance was compared to the performance of two groups of human observers: an expert group comprising orthopedic surgeons and radiologists, and a non-expert group, including emergency physicians and general practice doctors. We also carried out the external validation using two additional data sets to assess the generalizability of the model. Results: The Vit model showed exceptional performance in detecting non-displaced femoral neck fractures on paired AP and lateral hip radiographs, achieving a binary accuracy of 95.8% [95% confidence interval (CI): 94.9%, 96.8%] and an area under the curve (AUC) of 0.988. Compared to the human observers, the model had a higher accuracy of 96.7% (95% CI: 93.9%, 99.5%) on the paired AP and lateral hip radiographs, while the accuracy of the expert group was 90.5% (95% CI: 85.7%, 95.2%). Further, the model maintained good performance during the external validation, with an AUC of 0.959 on the paired AP and lateral views. Conclusions: Our Vit model showed expert-level performance in identifying non-displaced femoral neck fractures on paired AP and lateral hip radiographs. This model has the potential to enhance diagnosis accuracy and improve patient outcomes by reducing the need for additional examinations and preoperative time.

Cross-domain attention-guided generative data augmentation for medical image analysis with limited data.

Data augmentation is widely applied to medical image analysis tasks in limited datasets with imbalanced classes and insufficient annotations. However, traditional augmentation techniques cannot supply extra information, making the performance of diagnosis unsatisfactory. GAN-based generative methods have thus been proposed to obtain additional useful information to realize more effective data augmentation; but existing generative data augmentation techniques mainly encounter two problems: (i) Current generative data augmentation lacks of the capability in using cross-domain differential information to extend limited datasets. (ii) The existing generative methods cannot provide effective supervised information in medical image segmentation tasks. To solve these problems, we propose an attention-guided cross-domain tumor image generation model (CDA-GAN) with an information enhancement strategy. The CDA-GAN can generate diverse samples to expand the scale of datasets, improving the performance of medical image diagnosis and treatment tasks. In particular, we incorporate channel attention into a CycleGAN-based cross-domain generation network that captures inter-domain information and generates positive or negative samples of brain tumors. In addition, we propose a semi-supervised spatial attention strategy to guide spatial information of features at the pixel level in tumor generation. Furthermore, we add spectral normalization to prevent the discriminator from mode collapse and stabilize the training procedure. Finally, to resolve an inapplicability problem in the segmentation task, we further propose an application strategy of using this data augmentation model to achieve more accurate medical image segmentation with limited data. Experimental studies on two public brain tumor datasets (BraTS and TCIA) show that the proposed CDA-GAN model greatly outperforms the state-of-the-art generative data augmentation in both practical medical image classification tasks and segmentation tasks; e.g. CDA-GAN is 0.50%, 1.72%, 2.05%, and 0.21% better than the best SOTA baseline in terms of ACC, AUC, Recall, and F1, respectively, in the classification task of BraTS, while its improvements w.r.t. the best SOTA baseline in terms of Dice, Sens, HD95, and mIOU, in the segmentation task of TCIA are 2.50%, 0.90%, 14.96%, and 4.18%, respectively.

Extramedullary relapsed acute lymphoblastic leukemia presenting as asymptomatic acute kidney injury after hematopoietic stem cell transplantation.

Acute kidney injury (AKI) is a common complication in children with hematological malignancies. Although AKI due to infiltration of tumor cells in children is rare, it negatively impacts treatment outcomes and increases the risk of mortality. We introduce a case of a child with acute lymphoblastic leukemia (ALL) who experienced kidney relapse resulting in asymptomatic AKI after remission from treatment, to remind clinicians not to overlook the primary disease in clinical judgment. In cases of unexplained AKI, kidney biopsy should be performed when feasible to get an accurate diagnosis and scientific treatment. In brief, children with leukemia who have achieved remission after treatment still need regular monitoring of urine routine and kidney function.

MiR-210-3p enhances intermittent hypoxia-induced tumor progression via inhibition of E2F3.

PURPOSE: Intermittent hypoxia (IH) is a hallmark of obstructive sleep apnea (OSA), which is related to tumorigenesis and progression. Although micro-ribonucleic acid-210-3p (miR-210-3p) is correlated with hypoxia-induced tumor development, its role in the relationship between IH and tumor function remains poorly understood. The present work focused on elucidating the molecular mechanism through which miR-210-3p drives tumor progression under IH. METHODS: MiR-210-3p levels were quantified within tumor samples from patients with lung adenocarcinoma who had or did not have OSA. Correlations between miR-210-3p and polysomnographic variables were analyzed. For in vitro experiments, miR-210-3p was inhibited or overexpressed via transfection under IH conditions. Cell viability, growth, invasion and migration assays were carried out. For in vivo modeling of IH using mouse xenografts, a miR-210-3p antagomir was intratumorally injected, tumor biological behaviors were evaluated, and reverse transcription-quantitative polymerase chain reaction (RT-qPCR), immunohistochemistry and western blot were carried out for detecting miR-210-3p and E2F transcription factor 3 (E2F3) expression. RESULTS: For patients with lung adenocarcinoma and OSA, high miR-210-3p levels showed positive relation to polysomnographic variables, such as oxygen desaturation index, apnea-hypopnea index, and proportion of total sleep time with oxygen saturation in arterial blood < 90%. IH enhanced tumor viability, proliferation, migration, and invasion, downregulated E2F3 expression, and increased miR-210-3-p levels. miR-210-3p overexpression induced similar changes. These changes were reversed by miR-210-3p inhibition in vitro or miR-210-3p antagomir through intratumoral injection in vivo. CONCLUSIONS: IH-induced tumor development is driven through miR-210-3p by E2F3 suppression. MiR-210-3p represents a potential therapeutic target among patients with concomitant cancer and OSA.

Neferine inhibits the development of lung cancer cells by downregulating TGF-ß to regulate MST1/ROS-induced pyroptosis.

Non-small cell lung cancer (NSCLC) accounts for ~85% of all lung cancer cases. Neferine is used as a traditional Chinese medicine with many pharmacological effects, including antitumor properties; however, it has not been reported whether neferine plays an anticancer role by causing pyroptosis in NSCLC cells. We used two typical lung cancer cell lines, A549 and H1299, and 42 lung cancer tissue samples to investigate the regulatory effects of neferine on TGF-ß and MST1. We also treated lung cancer cells with different concentrations of neferine to study its effects on lung cancer cell survival, migration, invasion, and epithelial-mesenchymal transition (EMT) as well as on pyroptosis. Lentivirus-mediated gain-of-function studies of TGF-ß and MST1 were applied to validate the roles of TGF-ß and MST1 in lung cancer. Next, we used murine transplanted tumor models to evaluate the effect of neferine treatment on the metastatic capacity of lung cancer tissues. With increasing neferine concentration, the viability, migration, invasion, and EMT capacity of A549 and H1299 cells decreased, whereas pyroptosis increased. Neferine repressed TGF-ß expression to modulate the induction of reactive oxygen species (ROS) by MST1. Overexpression of TGF-ß in either in vitro or mouse-transplanted A549 cells restored the inhibitory effect of neferine on tumor development. Overexpression of MST1 clearly enhanced pyroptosis. Neferine contributed to pyroptosis by regulating MST1 expression through downregulation of TGF-ß to induce ROS formation. Therefore, our study shows that neferine can serve as an adjuvant therapy for NSCLC patients.

A novel pathogenic variant c.262delA in PBX1 causing oligomeganephronia identified using whole-exome sequencing and a literature review.

Oligomeganephronia (OMN) is a rare congenital renal hypoplasia reported more often in children than in adults. The diagnosis of OMN relies on renal biopsy and exhibits a significant reduction in the number of glomeruli and pronounced glomerular hypertrophy. Here, we report the case of an 8-year-old boy with recurrent proteinuria and abnormal external ears. A renal biopsy revealed large and rare glomeruli. The histological findings confirmed the diagnosis of OMN. Whole-exome sequencing of the patient revealed a new pathogenic variant in PBX1 (hg19, NM_002585, c.262delA, p.Thr88Glnfs*3). The PBX1 gene encodes a transcription factor whose pathogenic variants can result in congenital renal and urinary system anomalies, with or without hearing loss, abnormal ears, and developmental retardation (CAKUTED). This is the first report to detect PBX1 pathogenic variants in children with OMN, a novel phenotype of human PBX1 pathogenic variants. We performed functional prediction analyses of deletions in the corresponding structural domains. We summarized 27 cases of PBX1 single pathogenic variants reported between 2003 and 2023 in terms of truncating and missense pathogenic variants, which can deepen our understanding of the PBX1 structural domain and expand our knowledge of the PBX1 genotype and phenotype.

Full Endoscopy Combined with Allogeneic Bone Grafting for Benign Spinal Lesions: Technical Notes and Preliminary Clinical Results.

Benign lesions of the spine include benign tumors and tumor-like lesions of the spine, which usually occur in the thoracic and lumbar vertebrae. The incidence rate is low, accounting for about 1% of primary bone tumors. Few cases of endoscopic treatment of benign spinal lesions have been reported in the literature. Here, we introduce a new surgical technique using full endoscopy and allogeneic bone grafting to treat benign spinal lesions. All patients in this study successfully underwent the operation, and their pain was significantly relieved postoperatively. The patient VAS scores decreased from 3.07 ± 0.70 preoperatively to 0.33 ± 0.49 at the last follow-up visit (p < 0.05). The mean total blood loss (including drainage blood) was 16.67 ± 6.98 mL. The mean operative time was 63.33 ± 7.23 min. No patients developed numbness in the corresponding segmental distribution after surgery, none of the patients had serious postoperative complications, and none had focal recurrence during follow-up requiring reoperation. Patients reported symptom relief throughout the whole follow-up period. We believe that endoscopic surgery preserves the ligaments and soft tissues around the vertebral body, and that this technique is feasible with minimal trauma, rapid recovery, and good outcomes at short-term follow-up. This minimally invasive treatment modality offers a new option for the treatment of patients with benign spinal lesions.

Value of peripheral blood circulating tumor cell detection in the diagnosis of thoracic diseases and the prediction of severity.

Circulating tumor cell (CTC) detection, as a noninvasive liquid biopsy method, has been used in the diagnosis, prognostic indication, and monitoring of a variety of cancers. In this study, we aimed to investigate whether CTC detection could be used in the early diagnosis and prediction of severity of thoracic diseases. We enrolled 168 thoracic disease patients, all of whom underwent pathological biopsy. Carcinoembryonic antigen (CEA) and neuron-specific enolase (NSE) measurement was also performed in 146 patients. There were 131 cases of malignant thoracic diseases and 37 cases of benign lesions. We detected CTCs in a 5 ml peripheral blood sample with the CTCBiopsy® system and analyzed the value of CTC count for predicting disease severity. Of 131 patients with a diagnosis of thoracic malignancy, CTCs were found in blood samples from 122 patients. However, only 2 out of 37 patients with benign thoracic disease had no detectable CTCs. There was no significant correlation between CTC count and benign and malignant lesions (P = 0.986). However, among 131 patients who had been diagnosed with malignant lesions, 33 had lymph node metastasis or distant metastasis. The presence of CTCs was significantly correlated with metastasis (P = 0.016 OR = 1.14). The area under the receiver operating characteristic (ROC) curve was 0.625 (95% confidence interval (CI), 0.519 to 0.730 P = 0.032). In addition, with stage IA1 as the cutoff, all patients were further divided into an early-stage group and a late-stage group. CTC count was significantly correlated with disease progression (P = 0.031 OR = 1.11), with an area under the curve (AUC) of 0.599 (95% CI, 0.506-0.692 P = 0.47). The sensitivity and specificity of CTC detection for the diagnosis of disease stage were 72.3% and 45.5%, respectively. In addition, the cutoff of 2.5 CTCs was the same when predicting disease metastasis and staging. Furthermore, the combination of CTC count, demographic characteristics and tumor markers had better predictive significance for disease staging. CTC count can effectively indicate the stages and metastasis of thoracic diseases, but it cannot differentiate benign and malignant diseases.

The role of ferroptosis and endoplasmic reticulum stress in intermittent hypoxia-induced myocardial injury.

PURPOSE: Obstructive sleep apnea (OSA) is related to increased risk of cardiovascular disease. Ferroptosis is a form of programmed cell death characterized by iron overload and plays critical roles in myocardial injury. This study aimed to investigate the role of ferroptosis in intermittent hypoxia (IH)-induced myocardial injury involving endoplasmic reticulum stress (ERS). METHODS: AC16 human cardiomyocytes were exposed to IH or normoxia conditions. Mice were randomly grouped as follows: normal control (NC), IH, ferrostatin-1 + IH (FIH), and N-acetylcysteine + IH (AIH). The mRNA levels of GPX4, xCT, FTH1, and FACL4 in AC16 cells were detected by qRT-PCR. The protein levels of GPX4, xCT, NOX4, ATF4, CHOP, Bcl-2, and Bax in myocardial tissue were detected by Western blot analysis. RESULTS: The mRNA expression levels of GPX4 and xCT in AC16 cells were significantly lower in IH group than that of NC group. In IH mice, myocardial tissues were injured accompanied by increased level of ferroptosis and ERS. Inhibition of ferroptosis and treatment of N-acetylcysteine reduced ERS and myocardial injury in mice exposed to IH. In addition, compared to ferrostatin-1, N-acetylcysteine exerted a greater effect in relieving IH-induced myocardial damage and ERS. CONCLUSIONS: Ferroptosis was involved in IH-related myocardial injury accompanied by the activation of ERS. Inhibition of ferroptosis and acetylcysteine treatment alleviated IH-related myocardial injury, which may be a potential target for therapeutic approaches to OSA-induced myocardial injury.

The association between obstructive sleep apnea and lung nodule, carcinoembryonic antigen.

PURPOSE: The association between obstructive sleep apnea (OSA) and cancer risks gaining more and more attention. Data on the association between OSA and lung cancer risk are limited. This study is to investigate whether a link exists between low-dose computed tomography (LDCT) scanning of the chest findings, carcinoembryonic antigen (CEA) and OSA in patients suspected of OSA. METHODS: The cross-sectional study included patients aged 18 years or older who underwent continuous nocturnal polysomnography at our sleep center between February 2019 and November 2020. All subjects underwent chest LDCT and CEA. Patients with an apnea-hypopnea index (AHI) of ≥ 15/h were classified as clinically significant OSA group, whereas patients with an AHI < 15/h were classified as control group. RESULTS: A total of 277 patients were enrolled in the study. 176 patients were categorized into the OSA group, while 101 patients were categorized into the control group. There is no relationship between any OSA-related parameter and presence of lung nodule or presence of ≥ 6 mm lung nodule in the binary logistic regression analysis. OSA group demonstrated a significant higher value of CEA than control group. Stepwise multiple linear regression analysis showed that lowest O2 saturation (ß = - 0.256, p < 0.001), smoking status (ß = 0.156, p = 0.007) and age (ß = 0.153, p = 0.008) were independent predictors of elevated CEA. CONCLUSIONS: OSA was independently related to the elevated of serum CEA level, but not with presence of pulmonary nodule or ≥ 6 mm pulmonary nodule in LDCT. Further well-designed longitudinal studies with pathology available are needed to identify the association between OSA and risk of lung cancer.

Challenges of COPD Patients during the COVID-19 Pandemic.

Coronavirus disease 2019 (COVID-19) is a severe systemic infection that is a major threat to healthcare systems worldwide. According to studies, chronic obstructive pulmonary disease (COPD) patients with COVID-19 usually have a high risk of developing severe symptoms and fatality, but limited research has addressed the poor condition of COPD patients during the pandemic. This review focuses on the underlying risk factors including innate immune dysfunction, angiotensin converting enzyme 2 (ACE2) expression, smoking status, precocious differentiation of T lymphocytes and immunosenescence in COPD patients which might account for their poor outcomes during the COVID-19 crisis. Furthermore, we highlight the role of aging of the immune system, which may be the culprit of COVID-19. In brief, we list the challenges of COPD patients in this national pandemic, aiming to provide immune-related considerations to support critical processes in COPD patients during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and inspire immune therapy for these patients.

From COPD to Lung Cancer: Mechanisms Linking, Diagnosis, Treatment, and Prognosis.

Many studies have proved that the pathogenesis of the chronic obstructive pulmonary disease (COPD) and lung cancer is related, and may cause and affect each other to a certain extent. In fact, the change of chronic airway obstruction will continue to have an impact on the screening, treatment, and prognosis of lung cancer.In this comprehensive review, we outlined the links and heterogeneity between COPD and lung cancer and finds that factors such as gene expression and genetic susceptibility, epigenetics, smoking, epithelial mesenchymal transformation (EMT), chronic inflammation, and oxidative stress injury may all play a role in the process. Although the relationship between these two diseases have been largely determined, the methods to prevent lung cancer in COPD patients are still limited. Early diagnosis is still the key to a better prognosis. Thus, it is necessary to establish more intuitive screening evaluation criteria and find suitable biomarkers for lung cancer screening in high-risk populations with COPD. Some studies have indicated that COPD may change the efficacy of anti-tumor therapy by affecting the response of lung cancer patients to immune checkpoint inhibitors (ICIs). And for lung cancer patients with COPD, the standardized management of COPD can improve the prognosis. The treatment of lung cancer patients with COPD is an individualized, comprehensive, and precise process. The development of new targets and new strategies of molecular targeted therapy may be the breakthrough for disease treatment in the future.