{"title":"Sphingolipid metabolism dysregulation: A cause for lung cancer development, progression, and resistance to therapies","authors":"Cungui Mao","doi":"10.1016/j.pccm.2025.05.002","DOIUrl":"10.1016/j.pccm.2025.05.002","url":null,"abstract":"<div><div>Lung cancer remains a leading cause of cancer-related mortality worldwide. Sphingolipids, a diverse class of lipids featuring a sphingoid base backbone, play essential roles in cellular processes and membrane structure. Complex sphingolipids such as sphingomyelins and glycosphingolipids maintain membrane integrity, while their metabolites—ceramide, sphingosine, and their phosphorylated forms, ceramide-1-phosphate (C1P) and sphingosine-1-phosphate (S1P)—act as bioactive lipids involved in regulating key cellular functions. Ceramide and sphingosine are generally tumor-suppressive, promoting apoptosis and inhibiting cell proliferation, whereas C1P and S1P support tumor progression through enhanced cell survival, proliferation, angiogenesis, and metastasis. S1P exerts its effects via G protein-coupled S1P receptors (S1PRs) and intracellular pathways, while C1P acts primarily through intracellular signaling. Dysregulation of these metabolites contributes to lung cancer pathogenesis, influencing tumor survival and resistance to therapy. Targeting sphingolipid metabolism—either by enhancing ceramide and sphingosine levels or inhibiting C1P and S1P—has shown promise in preclinical models. Moreover, these sphingolipid metabolites hold potential as biomarkers for diagnosis and prognosis in lung cancer. This review explores the roles of sphingolipids in lung cancer biology, their impact on tumor progression, and their therapeutic potential.</div></div>","PeriodicalId":72583,"journal":{"name":"Chinese medical journal pulmonary and critical care medicine","volume":"3 2","pages":"Pages 88-96"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144490253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Temporal trends in the burden of tracheal, bronchial, and lung cancer in China and globally: A comprehensive analysis from 1990 to 2021","authors":"Xue Fan, Linxi Yin, Xuenan Hou, Qing Zhou","doi":"10.1016/j.pccm.2025.04.001","DOIUrl":"10.1016/j.pccm.2025.04.001","url":null,"abstract":"<div><h3>Background</h3><div>Tracheal, bronchial, and lung (TBL) cancer remains a leading cause of cancer-related deaths globally, with its burden influenced by aging populations, smoking, air pollution, and advances in treatment. China, as one of the most affected countries, faces significant challenges due to rapid industrialization and an aging population. This study aimed to systematically assess the temporal trends and disease burden of tracheal, bronchial, and lung cancer in China from 1990 to 2021, in comparison with global patterns, to provide evidence for targeted prevention and public health policymaking.</div></div><div><h3>Methods</h3><div>Using data from the Global Burden of Disease (GBD) database (1990–2021), this study analyzed trends in the incidence, prevalence, mortality, and disability-adjusted life years (DALYs) of TBL cancer in China and globally. Joinpoint regression analysis was applied to identify significant changes in trends over time, and the average annual percentage change (AAPC) was calculated to quantify the overall temporal trends. Statistical significance was evaluated using Permutation tests, with results reported as 95 % confidence intervals (95 % CI).</div></div><div><h3>Results</h3><div>In 2021, China accounted for 41.0 % (934,704 of 2,280,688) of global incident cases, 38.8 % (1,262,275 of 3,253,729) of global prevalent cases, 40.4 % (814,364 of 2,016,547) of global deaths, and 40.7 % (18,920,203 of 46,536,272) of global DALYs. The AAPC for China’s age-standardized incidence rate (ASIR), age-standardized prevalence rate (ASPR), age-standardized mortality rate (ASMR), and age-standardized DALYs rate (ASDR) were 0.9 % (95 % CI: 0.8 % to 1.1 %, <em>P</em> <em><</em> 0.05), 1.8 % (95 % CI: 1.6 % to 2.0 %, <em>P</em> <em><</em> 0.05), 0.4 % (95 % CI: 0.2 % to 0.6 %, <em>P</em> <em><</em> 0.05), and 0.1 % (95 % CI: 0.1 % to 2.0 %, <em>P</em> > 0.05), respectively, while the global AAPCs were −0.3 % (95 % CI: −0.4 % to −0.2 %, <em>P</em> <em><</em> 0.05), 0.3 % (95 % CI: 0.2 % to 0.4 %, <em>P</em> <em><</em> 0.05), −0.5 % (95 % CI: −0.7 to −0.4 %, <em>P</em> <em><</em> 0.05) and −0.9 % (95 % CI: −1.0 % to −0.8 %, <em>P</em> <em><</em> 0.05). Notably, over the last two decades, the growth rate of China’s ASIR has slowed, the ASMR and ASDR stopped rising and showed a significant decline compared to previous trends. The burden of TBL cancer varied by age and gender; over the past decade, the ASIR, ASMR, and ASDR for males in China have shown a declining trend, whereas the rates for females have increased. Additionally, the peak age of burden has shifted to older age groups compared to 1990.</div></div><div><h3>Conclusion</h3><div>China bears a significant share of the global burden of TBL cancer. Over the last two decades, the growth rate of China’s ASIR has slowed, while its ASMR and ASDR have declined, potentially attributable to advancements in targeted therapies and immunotherapies.</div></d","PeriodicalId":72583,"journal":{"name":"Chinese medical journal pulmonary and critical care medicine","volume":"3 2","pages":"Pages 120-131"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144490251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Burden of chronic obstructive pulmonary disease and risk factors in China from 1990 to 2021: Analysis of global burden of disease 2021","authors":"Fen Dong , Rui Su , Yu Ren , Ting Yang","doi":"10.1016/j.pccm.2025.05.004","DOIUrl":"10.1016/j.pccm.2025.05.004","url":null,"abstract":"<div><h3>Background</h3><div>Chronic obstructive pulmonary disease (COPD) is a common chronic disease that imposes tremendous burdens on the general populations in China and other countries worldwide. A comprehensive understanding of the contemporary epidemiological landscape of COPD is crucial for formulating effective prevention and control strategies. This study was designed to systematically evaluate the temporal trends in COPD burden and its associated risk factors in China over recent decades, providing evidence-based insights for targeted interventions.</div></div><div><h3>Methods</h3><div>We conducted a comprehensive analysis of the Global Burden of Disease (GBD) 2021 dataset to systematically evaluate COPD epidemiology in China from 1990 to 2021. Our study quantified key disease burden indicators including incident cases, prevalent cases, deaths, and disability-adjusted life years (DALYs), along with their corresponding crude rates and age-standardized rates, while examining their temporal trends. Furthermore, we stratified these metrics by demographic characteristics (sex and age groups) and assessed the population attributable fractions of major risk factors for COPD in the Chinese population.</div></div><div><h3>Results</h3><div>In 2021, China had an estimated 4.43 (95 % uncertainty interval [UI]: 4.01–4.86) million incident COPD cases and 50.59 (95 % UI: 44.98–57.12) million prevalent cases, accounting for nearly one-quarter of COPD prevalent cases worldwide. The crude COPD incidence and prevalence rates in China were 311.68 (95% UI: 281.75–341.62) per 100,000 and 3555.69 (95% UI: 3161.20–4014.55) per 100,000, respectively. Nearly 1.29 (95 % UI: 1.04–1.54) million individuals died from COPD, representing 10.99 % of deaths in China, and the crude mortality rate was 90.35 (95 % UI: 73.43–108.23) per 100,000. The DALYs were estimated at 23.64 (95 % UI: 20.00–27.92) million person years and the crude DALYs rate was 1661.60 (95 % UI: 1405.64–1962.54) per 100,000. The age-specific COPD incidence and prevalence rates increased substantially at 40 years of age and continued to rise thereafter. The mortality and DALY rates increased tremendously in elderly population. Sex disparities existed in the mortality and DALY rates, with both being markedly higher in men than in women, particularly among older adults aged >60 years, indicating non-optimal disease management in this population subgroup. Smoking was the leading risk factor for COPD deaths and DALYs, followed by particulate matter pollution and occupational exposure. The age-standardized rates for all metrics decreased substantially from 1990 to 2021, especially the mortality and DALY rates with decreases of 68.40 % and 68.13 %, respectively. Nevertheless, the numbers of incident and prevalent COPD cases increased, with both having doubled in 2021 compared with those in 1990.</div></div><div><h3>Conclusions</h3><div>While the age-standardized rates for COPD incidence, prevalence, mort","PeriodicalId":72583,"journal":{"name":"Chinese medical journal pulmonary and critical care medicine","volume":"3 2","pages":"Pages 132-140"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144490581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhong Cao , Liu He , Yuheng Luo , Xunliang Tong , Jinghan Zhao , Ke Huang , Qiushi Chen , Lirui Jiao , Yuhao Liu , Pascal Geldsetzer , Ting Yang , Chen Wang , Till Winfried Bärnighausen , Simiao Chen
{"title":"Burden of chronic respiratory diseases and their attributable risk factors in 204 countries and territories, 1990–2021: Results from the global burden of disease study 2021","authors":"Zhong Cao , Liu He , Yuheng Luo , Xunliang Tong , Jinghan Zhao , Ke Huang , Qiushi Chen , Lirui Jiao , Yuhao Liu , Pascal Geldsetzer , Ting Yang , Chen Wang , Till Winfried Bärnighausen , Simiao Chen","doi":"10.1016/j.pccm.2025.05.005","DOIUrl":"10.1016/j.pccm.2025.05.005","url":null,"abstract":"<div><h3>Background</h3><div>Chronic respiratory diseases (CRDs) remain a substantial global public health challenge, contributing significantly to morbidity and mortality worldwide. This study aimed to comprehensively characterize trends in CRD burden across various populations by examining differences by sex, age, and sociodemographic index (SDI).</div></div><div><h3>Methods</h3><div>We performed a systematic analysis using data from the Global Burden of Disease (GBD) 2021 study, covering the period from 1990 to 2021 across 204 countries and territories. Estimates of age-standardized prevalence, mortality, disability-adjusted life years (DALYs), incidence, and annualized percentage changes for both 1990–2021 and 2019–2021 were calculated. Geographic and demographic variations were evaluated by age, sex, and SDI. The contributions of key risk factors—including tobacco use, ambient particulate matter (PM) pollution, household air pollution from solid fuels, and occupational exposure to PM, gases, and fumes—were also assessed.</div></div><div><h3>Results</h3><div>In 2021, an estimated 468.3 million individuals globally were living with CRDs, with an age-standardized prevalence rate of 5785.4 per 100,000 population. CRDs accounted for 4.4 million deaths with age-standardized mortality rate of 53.6 per 100,000 population and 108.5 million DALYs with age-standardized DALY rate of 1294.6 per 100,000 population in the same year. Age-standardized prevalence rate decreased by 1.01 % from 1990 to 2021 but increased by 0.20 % from 2019 to 2021. From 2019 to 2021, the age-standardized incidence rate of CRDs increased slightly from 713.4 to 719.3 per 100,000 population, with an annualized percentage change of 0.41 %, while the age-standardized DALY rate continued to decline from 1321.9 to 1294.6 per 100,000 population, with an annualized percentage change of −1.04 %. Although the age-standardized mortality rate declined by 1.46 % over the full period, the absolute number of deaths rose as a result of demographic shifts, including population growth and aging. Globally, tobacco use remained the predominant risk factor, while household air pollution from solid fuels was the leading contributor to DALYs and mortality in low- and low-middle SDI countries.</div></div><div><h3>Conclusion</h3><div>The global burden of CRDs remains both substantial and dynamic, underscoring the continued influence of risk factors such as tobacco use and household air pollution. These findings emphasize the urgent need for targeted public health interventions and more equitable healthcare resource allocation, particularly in low- and middle-SDI regions. Strengthened surveillance systems, improved access to care, and integrated strategies addressing both established and emerging risk factors are essential for reducing the global impact of CRDs.</div></div>","PeriodicalId":72583,"journal":{"name":"Chinese medical journal pulmonary and critical care medicine","volume":"3 2","pages":"Pages 100-110"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144490255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Corrigendum to “Quan M, Guo Q, Yan X, et al. Parkin deficiency aggravates inflammation-induced acute lung injury by promoting necroptosis in alveolar type II cells” [Chin Med J Pulm Crit Care Med 2024;2:265-278]","authors":"","doi":"10.1016/j.pccm.2025.01.002","DOIUrl":"10.1016/j.pccm.2025.01.002","url":null,"abstract":"","PeriodicalId":72583,"journal":{"name":"Chinese medical journal pulmonary and critical care medicine","volume":"3 1","pages":"Page 63"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143715470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Guide for Authors","authors":"","doi":"10.1016/S2772-5588(25)00018-0","DOIUrl":"10.1016/S2772-5588(25)00018-0","url":null,"abstract":"","PeriodicalId":72583,"journal":{"name":"Chinese medical journal pulmonary and critical care medicine","volume":"3 1","pages":"Pages 66-76"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143715472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lishu Zhao , Chen Tang , Xuan Jin , Hao Wang , Kandi Xu , Xinyue Liu , Yujin Liu , Wencheng Zhao , Wengang Zhang , Li Ye , Zhimin Chen , Qi Liu , Yayi He
{"title":"Unraveling tumoral heterogeneity and angiogenesis-associated mechanisms of PD-1 and LAG-3 dual inhibition in lung cancers by single-cell RNA sequencing","authors":"Lishu Zhao , Chen Tang , Xuan Jin , Hao Wang , Kandi Xu , Xinyue Liu , Yujin Liu , Wencheng Zhao , Wengang Zhang , Li Ye , Zhimin Chen , Qi Liu , Yayi He","doi":"10.1016/j.pccm.2025.02.004","DOIUrl":"10.1016/j.pccm.2025.02.004","url":null,"abstract":"<div><h3>Background</h3><div>Lymphocyte activation gene 3 (LAG-3) is a promising immune checkpoint for combination immunotherapy. This study aims to elucidate the exact synergistic anti-tumor mechanism of programmed death 1 (PD-1) and LAG-3 dual inhibition in lung cancer.</div></div><div><h3>Methods</h3><div>Multiple patient-derived xenograft (PDX) models of lung cancer were constructed and analyzed by single-cell RNA sequencing (scRNA-seq). Clustering of all human-derived cells, identification of biomarker genes of three cell types, trajectory analysis, and calculation of tumor heterogeneity scores were performed. Differentially expressed genes (DEGs) were identified and functional enrichment analyses of cancer-associated genes were conducted. The functional significance of DEGs in the immune system was evaluated using the Reactome online server. Major histocompatibility complex (MHC) pathways and angiogenesis-associated pathways were analyzed. The Cancer Genome Atlas (TCGA) was used for further verification.</div></div><div><h3>Results</h3><div>PD-1 and LAG-3 dual inhibition achieved synergistic tumor inhibition in squamous cell carcinoma (SCC) PDX models, but not in adenocarcinoma and small cell lung cancer PDX models. A total of 8127 cells, including 2699 basal, 4109 malignant, and 1319 epithelial cells, were identified by scRNA-seq. Malignant cells evolved from basal and epithelial cells in the trajectory analysis. The responders to the combination therapy of PD-1 and LAG-3 inhibitors had lower heterogeneity scores than non-responders. Compared with anti-PD-1 monotherapy, the combination group exhibited higher levels of neutrophil degranulation. The DEGs were correlated with disease, metabolism, and programmed cell death-associated pathways. The MHC class I-associated pathways and pericyte pathways were upregulated, whereas the vascular endothelial growth factor pathway was downregulated in the combination group.</div></div><div><h3>Conclusion</h3><div>We discovered the superior efficacy of PD-1 and LAG-3 dual inhibition in SCC PDX models, and showed that it may be associated with low tumor heterogeneity scores, upregulation of the MHC class I pathway, and normalization of tumor angiogenesis.</div></div>","PeriodicalId":72583,"journal":{"name":"Chinese medical journal pulmonary and critical care medicine","volume":"3 1","pages":"Pages 41-49"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143715444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Advances in pathophysiology and assessment methods of chronic obstructive pulmonary disease with frailty","authors":"Xia Wang, Weiping Hu, Jing Zhang","doi":"10.1016/j.pccm.2025.02.002","DOIUrl":"10.1016/j.pccm.2025.02.002","url":null,"abstract":"<div><div>Frailty, a multidimensional syndrome characterized by decreased physiological reserves and vulnerability to stressors, presents significant challenges in the management of chronic obstructive pulmonary disease (COPD). COPD and frailty share common risk factors and pathophysiological pathways, such as muscle wasting, chronic inflammation, and malnutrition. Both COPD and frailty lead to a significant reduction in patients’ physical functionality and quality of life. Consequently, early screening for frailty and proactive interventions for patients with COPD are increasingly considered essential. There are several methods for screening and assessing frailty in patients with COPD, such as the Fried Frailty Phenotype and the Frailty Index, each with its own advantages and limitations. However, there is currently no unified standard, nor a method specifically tailored to the Chinese population. The treatment of patients with COPD and concurrent frailty currently favors exercise interventions, nutritional interventions, or a combination of both. Further treatment approaches, including pharmacological interventions, are still being explored. Therefore, the development of frailty screening and assessment tools tailored to the Chinese population, along with the exploration of reasonable and effective new intervention measures, represents a crucial direction in China's efforts to prevent and treat frailty.</div></div>","PeriodicalId":72583,"journal":{"name":"Chinese medical journal pulmonary and critical care medicine","volume":"3 1","pages":"Pages 22-28"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143715475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Overlapping exposure to cigarette smoke and particulate matter does not have a direct additive effect on chronic obstructive pulmonary disease","authors":"Lifeng Yan , Huaqi Guo , Juan Fu , Tianyu Zhou","doi":"10.1016/j.pccm.2025.02.006","DOIUrl":"10.1016/j.pccm.2025.02.006","url":null,"abstract":"","PeriodicalId":72583,"journal":{"name":"Chinese medical journal pulmonary and critical care medicine","volume":"3 1","pages":"Pages 60-62"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143715446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}