Chinese medical journal pulmonary and critical care medicine最新文献

Cellular senescence is a status of irreversible growth arrest, which can be triggered by the p53/p21^cip1 and p16^INK4/Rb pathways via intrinsic and external factors. Senescent cells are typically enlarged and flattened, and characterized by numerous molecular features. The latter consists of increased surfaceome, increased residual lysosomal activity at pH 6.0 (manifested by increased activity of senescence-associated beta-galactosidase [SA-β-gal]), senescence-associated mitochondrial dysfunction, cytoplasmic chromatin fragment, nuclear lamin b1 exclusion, telomere-associated foci, and the senescence-associated secretory phenotype. These features vary depending on the stressor leading to senescence and the type of senescence. Cellular senescence plays pivotal roles in organismal aging and in the pathogenesis of aging-related diseases. Interestingly, senescence can also both promote and inhibit wound healing processes. We recently report that senescence as a programmed process contributes to normal lung development. Lung senescence is also observed in Down Syndrome, as well as in premature infants with bronchopulmonary dysplasia and in a hyperoxia-induced rodent model of this disease. Furthermore, this senescence results in neonatal lung injury. In this review, we briefly discuss the molecular features of senescence. We then focus on the emerging role of senescence in normal lung development and in the pathogenesis of bronchopulmonary dysplasia as well as putative signaling pathways driving senescence. Finally, we discuss potential therapeutic approaches targeting senescent cells to prevent perinatal lung diseases.

Lung cancer is a leading cause of cancer deaths worldwide, consisting of two major histological subtypes: small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC). In some cases, NSCLC patients may undergo a histological transformation to SCLC during clinical treatments, which is associated with resistance to targeted therapy, immunotherapy, or chemotherapy. The review provides a comprehensive analysis of SCLC transformation from NSCLC, including biological mechanism, clinical relevance, and potential treatment options after transformation, which may give a better understanding of SCLC transformation and provide support for further research to define better therapy options.

Background

Light at night (LAN) has become a concern in interdisciplinary research in recent years. This global interdisciplinary study aimed to explore the exposure–lag–response association between LAN exposure and lung cancer incidence.

Methods

LAN data were obtained from the Defense Meteorological Satellite Program's Operational Linescan System. Data of lung cancer incidence, socio-demographic index, and smoking prevalence of populations in 201 countries/territories from 1992 to 2018 were collected from the Global Burden of Disease Study. Spearman correlation tests and population-weighted linear regression analysis were used to evaluate the correlation between LAN exposure and lung cancer incidence. A distributed lag nonlinear model (DLNM) was used to assess the exposure–lag effects of LAN exposure on lung cancer incidence.

Results

The Spearman correlation coefficients were 0.286–0.355 and the population-weighted linear regression correlation coefficients were 0.361–0.527. After adjustment for socio-demographic index and smoking prevalence, the Spearman correlation coefficients were 0.264–0.357 and the population-weighted linear regression correlation coefficients were 0.346–0.497. In the DLNM, the maximum relative risk was 1.04 (1.02–1.06) at LAN exposure of 8.6 with a 2.6-year lag time. After adjustment for socio-demographic index and smoking prevalence, the maximum relative risk was 1.05 (1.02–1.07) at LAN exposure of 8.6 with a 2.4-year lag time.

Conclusion

High LAN exposure was associated with increased lung cancer incidence, and this effect had a specific lag period. Compared with traditional individual-level studies, this group-level study provides a novel paradigm of effective, efficient, and scalable screening for risk factors.

Progressive lung fibrosis is characterized by dysregulated extracellular matrix (ECM) homeostasis. Understanding of disease pathogenesis remains limited and has prevented the development of effective treatments. While an abnormal wound-healing response is strongly implicated in lung fibrosis initiation, factors that determine why fibrosis progresses rather than regular tissue repair occur are not fully explained. Within human lung fibrosis, there is evidence of altered epithelial and mesenchymal populations as well as cells undergoing epithelial–mesenchymal transition (EMT), a dynamic and reversible biological process by which epithelial cells lose their cell polarity and down-regulate cadherin-mediated cell–cell adhesion to gain migratory properties. This review will focus on the role of EMT and dysregulated epithelial–mesenchymal crosstalk in progressive lung fibrosis.

Background

The impact of corticosteroids on humoral responses in coronavirus disease 2019 (COVID-19) survivors during the acute phase and subsequent 6-month period remains unknown. This study aimed to determine how the use of corticosteroids influences the initiation and duration of humoral responses in COVID-19 survivors 6 months after infection onset.

Methods

We used kinetic antibody data from the lopinavir–ritonavir trial conducted at Jin Yin-Tan Hospital in January 2020, which involved adults hospitalized with severe COVID-19 (LOTUS, ChiCTR2000029308). Antibody samples were collected from 192 patients during hospitalization, and kinetic antibodies were monitored at all available time points after recruitment. Additionally, plasma samples were collected from 101 COVID-19 survivors for comprehensive humoral immune measurement at the half-year follow-up visit. The main focus was comparing the humoral responses between patients treated with systemic corticosteroid therapy and the non-corticosteroid group.

Results

From illness onset to day 30, the median antibody titre areas under the receiver operating characteristic curve (AUCs) of nucleoprotein (N), spike protein (S), and receptor-binding domain (RBD) immunoglobulin G (IgG) were significantly lower in the corticosteroids group. The AUCs of N-, S-, and RBD-IgM as well as neutralizing antibodies (NAbs) were numerically lower in the corticosteroids group compared with the non-corticosteroid group. However, peak titres of N, S, RBD-IgM and -IgG and NAbs were not influenced by corticosteroids. During 6-month follow-up, we observed a delayed decline for most binding antibodies, except N-IgM (β −0.05, 95% CI [−0.10, 0.00]) in the corticosteroids group, though not reaching statistical significance. No significant difference was observed for NAbs. However, for the half-year seropositive rate, corticosteroids significantly accelerated the decay of IgA and IgM but made no difference to N-, S-, and RBD-IgG or NAbs. Additionally, corticosteroids group showed a trend towards delayed viral clearance compared with the non-corticosteroid group, but the results were not statistically significant (adjusted hazard ratio 0.71, 95% CI 0.50–1.00; P = 0.0508).

Conclusion

Our findings suggested that corticosteroid therapy was associated with impaired initiation of the antibody response but this did not compromise the peak titres of binding and neutralizing antibodies. Throughout the decay phase, from the acute phase to the half-year follow-up visit, short-term and low-dose corticosteroids did not significantly affect humoral responses, except for accelerating the waning of short-lived antibodies.

Alveoli serve as the functional units of the lungs, responsible for the critical task of blood–gas exchange. Comprising type I (AT1) and type II (AT2) cells, the alveolar epithelium is continuously subject to external aggressors like pathogens and airborne particles. As such, preserving lung function requires both the homeostatic renewal and reparative regeneration of this epithelial layer. Dysfunctions in these processes contribute to various lung diseases. Recent research has pinpointed specific cell subgroups that act as potential stem or progenitor cells for the alveolar epithelium during both homeostasis and regeneration. Additionally, endothelial cells, fibroblasts, and immune cells synergistically establish a nurturing microenvironment—or “niche”—that modulates these epithelial stem cells. This review aims to consolidate the latest findings on the identities of these stem cells and the components of their niche, as well as the molecular mechanisms that govern them. Additionally, this article highlights diseases that arise due to perturbations in stem cell–niche interactions. We also discuss recent technical innovations that have catalyzed these discoveries. Specifically, this review underscores the heterogeneity, plasticity, and dynamic regulation of these stem cell–niche systems. It is our aspiration that a deeper understanding of the fundamental cellular and molecular mechanisms underlying alveolar homeostasis and regeneration will open avenues for identifying novel therapeutic targets for conditions such as chronic obstructive pulmonary disease (COPD), fibrosis, coronavirus disease 2019 (COVID-19), and lung cancer.

Asthma, a chronic respiratory disease with a global prevalence of approximately 300 million individuals, presents a significant societal and economic burden. This multifaceted syndrome exhibits diverse clinical phenotypes and pathogenic endotypes influenced by various factors. The advent of omics technologies has revolutionized asthma research by delving into the molecular foundation of the disease to unravel its underlying mechanisms. Omics technologies are employed to systematically screen for potential biomarkers, encompassing genes, transcripts, methylation sites, proteins, and even the microbiome components. This review provides an insightful overview of omics applications in asthma research, with a special emphasis on genetics, transcriptomics, epigenomics, and the microbiome. We explore the cutting-edge methods, discoveries, challenges, and potential future directions in the realm of asthma omics research. By integrating multi-omics and non-omics data through advanced statistical techniques, we aspire to advance precision medicine in asthma, guiding diagnosis, risk assessment, and personalized treatment strategies for this heterogeneous condition.