Immune checkpoint blockade (ICB) therapy has demonstrated significant efficacy in the treatment of various cancers. However, a subset of patients develops hyper-progressive disease (HPD) following ICB, which is characterized by accelerated tumor growth and poor clinical outcomes. This review outlines the clinical features, potential mechanisms, and possible intervention strategies of HPD, with the aim of informing clinical practice and providing relevant recommendations. .
Lung cancer remains one of the most prevalent and lethal malignancies worldwide. The advancement of its precise diagnosis and therapeutic development urgently requires in vitro models that can highly recapitulate the pathophysiological characteristics of human tissues. Organ-on-a-chip has emerged as a novel technological platform that integrates microfluidic engineering, biomaterials, and other engineering strategies with organoid culture. This platform enables precise control over the cellular microenvironment, thereby closely mimicking the three-dimensional structure and physiological functions of human organs in vitro. Organ-on-a-chip systems demonstrate significant advantages in cancer research, developmental biology, and disease modeling, as they not only preserve the heterogeneity and pathological features of patient samples but also support co-culture of various cell types to reconstruct the tumor microenvironment (TME). However, standardized construction methods and integrated analytical strategies for this technology in lung cancer research remain to be further refined. This review systematically elaborates on the key technical principles of organ-on-a-chip and its recent advances in lung cancer modeling, drug screening, and immunotherapy research. It aims to provide a theoretical foundation and technical perspective for promoting the deeper application of organ-on-a-chip in precision medicine and translational research for lung cancer. .
Combined small cell lung cancer (CSCLC) is a cancer that mixes small cell lung cancer (SCLC) with non-small cell lung cancer (NSCLC) components according to the World Health Organization's 2015 New Pathologic Classification of Lung Cancer. Composed of a mixture of SCLC and NSCLC components, CSCLC is classified as a subtype of SCLC in neuroendocrine tumors. Currently, research on SCLC mainly focuses on single-component pure SCLC, with relatively few studies on CSCLC, which is clinically rare and has no standardized treatment protocols and lacks a unified perception of the clinicopathological features and prognostic predictive indexes of CSCLC. Further observation of efficacy and prognosis is needed. We report the treatment course of a case of CSCLC and provide a literature review of the current status of research on CSCLC. .
Background: Double-stranded RNA-specific adenosine deaminase 1 (ADAR1) binds to double-stranded RNA and catalyzes the deamination of adenosine (A) to inosine (I). The functional mechanism of ADAR1 in non-small cell lung cancer (NSCLC) remains incompletely understood. This study aimed to investigate the prognostic significance of ADAR1 in NSCLC and to elucidate its potential role in regulating tumor cell proliferation and migration.
Methods: Data from The Cancer Genome Atlas (TCGA) and cBioPortal were analyzed to assess the correlation between high ADAR1 expression and clinicopathological features as well as prognosis in lung cancer. We performed Western blot (WB), cell proliferation assays, Transwell invasion/migration assays, and nude mouse xenograft modeling to examine the phenotypic changes and molecular mechanisms induced by ADAR1 knockdown. Furthermore, the ADAR1 p150 overexpression model was utilized to validate the proposed mechanism.
Results: ADAR1 expression was significantly elevated in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) tissues compared with adjacent non-tumor tissues (LUAD: P=3.70×10-15, LUSC: P=0.016). High ADAR1 expression was associated with poor prognosis (LUAD: P=2.03×10-2, LUSC: P=2.81×10-2) and distant metastasis (P=0.003). Gene Set Enrichment Analysis (GSEA) indicated that elevated ADAR1 was associated with mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway activation, matrix metalloproteinase-9 (MMP-9) expression, and cell adhesion. ADAR1 and MMP-9 levels showed a strongly positive correlation (P=6.45×10-34) in 10 lung cancer cell lines, highest in H1581. Knockdown of ADAR1 in H1581 cells induced a rounded cellular morphology with reduced pseudopodia. Concomitantly, it suppressed cell proliferation, invasion, migration, and in vivo tumorigenesis. It also suppressed ERK phosphorylation and downregulated cellular Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog (c-FOS), MMP-9, N-cadherin, and Vimentin. Conversely, ADAR1 p150 overexpression in PC9 cells enhanced ERK phosphorylation and increased c-FOS and MMP-9 expression.
Conclusions: High ADAR1 expression is closely associated with poor prognosis and distant metastasis in NSCLC patients. Mechanistically, ADAR1 may promote proliferation, invasion, migration, and tumorigenesis in lung cancer cells via the ERK/c-FOS/MMP-9 axis.
Background: For lung transplant recipients (LTRs), rehabilitation management after lung transplantation is a crucial link affecting the recovery of pulmonary function. This study systematically summarizes and generalizes the relevant evidences on postoperative pulmonary function rehabilitation management in LTRs, thereby providing a basis for formulating clinical strategies for postoperative pulmonary function rehabilitation management in this patient population.
Methods: Based on the "6S" evidence model, a systematic search was conducted in domestic and international databases and websites, including UpToDate, BMJ Best Practice, Cochrane Library, Web of Science, China Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Wanfang Database, Guidelines International Network (GIN), and China Yimai Tong Guidelines Network, from the establishment of each database to July 2025. Relevant evidences on postoperative pulmonary function rehabilitation management for LTRs were extracted, and two researchers independently conducted quality assessment, evidence extraction, and integration of the included literature.
Results: A total of 18 studies were included, consisting of 3 expert consensuses, 4 systematic reviews/evidence summaries, 4 randomized controlled trials (RCTs), 5 quasi-experimental studies, and 2 cohort studies. A total of 30 pieces of best evidence were summarized, covering 8 themes: rehabilitation assessment, early intervention, exercise training, nutritional management, medication management, respiratory function training, psychological support, and long-term follow-up.
Conclusions: Based on evidence-based principles, this study summarizes the best evidence for postoperative pulmonary function rehabilitation training in LTRs and proposes 30 clinically applicable recommendations, which provides a theoretical basis for the clinical implementation of pulmonary function rehabilitation management. Clinical medical and nursing staff should combine specific clinical scenarios and professional judgments to translate the evidence into practice, and provide scientific rehabilitation management and guidance for LTRs.
Malignant pleural effusion (MPE) refers to the accumulation of pleural fluid caused by metastasis from primary pleural malignancies or tumors originating elsewhere. It is associated with a poor prognosis. Current treatment strategies primarily include systemic anti-tumor therapy and local management of MPE based on the primary tumor. Numerous studies have documented diverse approaches for the local control of MPE. This review summarizes recent advances in local treatment strategies for primary tumor-related MPE, highlighting emerging pharmacological agents and innovative techniques. .
Human epidermal growth factor receptor 2 (HER2) mutations play a role as a driver gene in non-small cell lung cancer (NSCLC). Patients with advanced NSCLC harboring HER2 mutations exhibit poor responses to conventional chemotherapy and immunotherapy, hence targeted therapies against HER2 are under extensive investigation. This review analyzes the biological characteristics of HER2, an overview of clinical trials for targeted therapy drugs, including monoclonal antibodies, tyrosine kinase inhibitors (TKIs), and antibody-drug conjugate, and research directions for drug resistance in NSCLC. Currently, Pyrotinib and Trastuzumab deruxtecan have been approved for the treatment of advanced NSCLC with HER2 mutations, suitable for patients who have failed standard therapy, which is far from meeting the clinical demands. Novel selective HER2 TKIs are gradually emerging. Future exploration trends are gradually shifting from single drugs to combination strategies, and are exploring more precise selection strategies as well as research on resistance mechanisms. These studies will provide a theoretical basis for clinical treatment strategies for advanced NSCLC with HER2 mutations, promoting the development of personalized therapy. .
Immune checkpoint inhibitors (ICIs) have been approved for the treatment of a variety of solid tumors and hematological malignancies. Adverse reactions caused by ICIs have been gradually focused on. Cytomegalovirus (CMV) gastritis after ICIs treatment is relatively rare. Here we reported a case of advanced lung adenocarcinoma who experienced recurrent upper abdominal pain and vomiting after Pembrolizumab treatment. CMV gastritis was diagnosed through gastroscopy. The patient's symptoms improved after antiviral treatment. During the treatment of ICIs, attention should be paid to the differential diagnosis of upper abdominal pain symptoms, and vigilance should be maintained against CMV gastritis. It is difficult to differentiate CMV gastritis and immune-related gastritis judging from symptoms, and gastroscopy is important for differential diagnosis. .
Background: Lung adenocarcinoma is an important pathohistologic subtype of non-small cell lung cancer (NSCLC). Invasive non-mucinous pulmonary adenocarcinomas (INMA) tend to have a poor prognosis due to their significant heterogeneity and diverse histologic components. Establishing a histologic grading system for INMA is crucial for evaluating its malignancy. In 2021, the International Association for the Study of Lung Cancer (IASLC) proposed that a new histological grading system could better stratify the prognosis of INMA patients. The aim of this study was to establish a visualized nomogram model to predict INMA IASLC grading preoperatively by means of dual-energy computed tomography (DECT), fractal dimension (FD), clinical features and conventional CT parameters.
Methods: A total of 112 patients with INMA who underwent preoperative DECT were retrospectively enrolled from March 2021 to January 2025. Patients were categorized into low-intermediate grade and high grade groups based on IASLC grading. The clinical characteristics and conventional CT parameters, including baseline features, biochemical markers, and serum tumor markers, were collected. DECT-derived parameters, including iodine concentration (IC), effective atomic number (eff-Z), and normalized IC (NIC), were collected and determined as NIC ratio (NICr) and fractal dimension (FD). Univariate analysis was employed to compare differences in conventional characteristics and DECT parameters between the two groups. Variables demonstrating statistical significance were subsequently incorporated into a multivariate Logistic regression analysis. A nomogram model integrating clinical data, conventional CT parameters, and DECT parameters was developed to identify independent predictors for IASLC grading of INMA. The discriminatory performance of the model was evaluated using receiver operating characteristic (ROC) curve analysis.
Results: Multivariate analysis identified smoking history [odds ratio (OR)=2.848, P=0.041], lobulation sign (OR=2.163, P=0.004), air bronchogram (OR=7.833, P=0.005), eff-Z in arterial phase (OR=4.266, P<0.001), and IC in arterial phase (OR=1.290, P=0.012) as independent and significant predictors for IASLC grading of INMA. The nomogram model constructed based on these indicators demonstrated optimal predictive performance, achieving an area under the curve (AUC) of 0.804 (95%CI: 0.725-0.883), with specificity and sensitivity of 85.3% and 65.7%, respectively.
Conclusions: The nomogram model based on clinical features, imaging features and spectral CT parameters have a large potential for application in the preoperative noninvasive assessment of INMA IASLC grading.
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