Lung Blood Research Articles

Complete remission after pembrolizumab monotherapy in a non-small cell lung cancer patient with PD-L1 negative, high tumor mutational burden, and positive tumor-infiltrating lymphocytes: A case report.

Immune checkpoint inhibitors have been used to treat cancer patients. Non-small cell lung cancer (NSCLC) patients with a high expression level of programmed cell death ligand-1 (PD-L1) could benefit from immune checkpoint inhibitor monotherapy. However, treating NSCLC patients with PD-L1 negative is still a clinical challenge. The utilization of new-type tumor markers as predictive indicators of therapeutic efficacy, with the aim of guiding clinical medication strategies, has emerged as a paramount focus of clinical investigation and interest. We reported a 72-year-old male with cough diagnosed as poorly differentiated metastatic lung adenocarcinoma (cT3N2M1, stage IV). He tested negative for driver gene mutations, and PD-L1 negative (＜1%), but a high tumor mutational burden (30.9 and 39.1 mutations/Mb in the lung tissue and blood, respectively), and positive tumor-infiltrating lymphocytes. The patient received pembrolizumab monotherapy. After 8 treatment cycles over 5 months, repeat examinations showed significantly reduced lung mass and circulating tumor DNA abundance. The patient reached clinical complete remission and had long-term survival with no significant adverse events. A comprehensive evaluation of multiple tumor biomarkers should be considered in NSCLC patients. Pembrolizumab monotherapy could benefit NSCLC patients with negative driver genes, PD-L1 negative, a high tumor mutational burden, and positive tumor-infiltrating lymphocytes.

Human adenovirus type 7 (HAdV-7) infection induces pulmonary vascular endothelial injury through the activation of endothelial autophagy

BackgroundHAdV-7 is a prevalent pathogen that can cause severe pneumonia in children. Previous studies have shown a significant increase in serum levels of vascular permeability factor (VPF/VEGF) and viral load in pediatric patients with fatal HAdV-7 infection, suggesting potential damage to the pulmonary vascular endothelium. Further research is necessary to elucidate the underlying mechanism.MethodsThe human lung microvascular endothelial cell line-5a and human CD46 mice were used for in vitro and in vivo experiments, respectively. RNA-seq was employed for correlative omics analysis. Viral infection and copy status were examined using transmission electron microscopy to observe virus particles, immunofluorescence to detect the viral protein Hexon, and qPCR to assess HAdV-7 fiber gene copies. Various methods, including ELISAs for VEGF and other injury markers, the CCK8 assay for cell viability, and flow cytometry for endothelium numbers, were employed to evaluate endothelial damage. Acute lung injury severity was evaluated by scoring pathological inflammation and measuring pulmonary vascular permeability. Autophagy activation was assessed by observing autophagosomes and validating marker proteins.ResultsGSEA analysis showed significant enrichment of gene sets related to endothelial functions (barrier, defense, and regeneration) and ALI in the HAdV-7-infected group. GO analysis indicated an enrichment of autophagy-related pathways linked to cell death. Subsequently, successful signs of HAdV-7 infection and replication were observed in the endothelium, including cytopathic effects, intracellular virions, and increased HAdV-7 fiber gene copies. Endothelial injury, including mitochondrial damage, decreased endothelium, and elevated levels of endothelial injury markers such as VEGF, sICAM-1, sVCAM-1, E-selectin, ESM1, MCP1, and IL1β were observed after HAdV-7 infection. Additionally, evidence of leaky lung blood vessels and ALI was observed, including progressive weight loss, elevated pulmonary vascular permeability, and severe lung consolidation. Furthermore, HAdV-7 infection induced autophagosome formation in the endothelium and triggered complete cell autophagy. Importantly, inhibiting autophagic flux reduced VEGF levels and other endothelial injury markers, decreased viral load, improved cell survival rate, alleviated pulmonary vessel leakage, and mitigated lung inflammation.ConclusionsHAdV-7 successfully infects pulmonary vascular endothelium and replicates effectively, causing injury to the endothelium, high VEGF expression and viral load in the serum, as well as ALI/ARDS. Autophagy inhibitors can alleviate endothelial injury, inhibit viral replication, relieve leakage from the vasculature, and reduce lung inflammation.

Impact of Viral Lower Respiratory Tract Infection (LRTI) in Early Childhood (0-2 Years) on Lung Growth and Development and Lifelong Trajectories of Pulmonary Health: A National Institutes of Health (NIH) Workshop Summary.

Viral lower respiratory tract infections (LRTI) are ubiquitous in early life. They are disproportionately severe in infants and toddlers (0-2 years), leading to more than 100,000 hospitalizations in the United States per year. The recent relative resilience to severe Coronavirus disease (COVID-19) observed in young children is surprising. These observations, taken together, underscore current knowledge gaps in the pathogenesis of viral lower respiratory tract diseases in young children and respiratory developmental immunology. Further, early-life respiratory viral infections could have a lasting impact on lung development with potential life-long pulmonary sequelae. Modern molecular methods, including high-resolution spatial and single-cell technologies, in concert with longitudinal observational studies beginning in the prenatal period and continuing into early childhood, promise to elucidate developmental pulmonary and immunophenotypes following early-life viral infections and their impact on trajectories of future respiratory health. In November 2019, under the auspices of a multi-disciplinary Workshop convened by the National Heart Lung Blood Institute and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, experts came together to highlight the challenges of respiratory viral infections, particularly in early childhood, and emphasize the knowledge gaps in immune, virological, developmental, and clinical factors that contribute to disease severity and long-term pulmonary morbidity from viral LRTI in children. We hope that the scientific community will view these challenges in clinical care on pulmonary health trajectories and disease burden not as a window of susceptibility but as a window of opportunity.

Whole-body-electro-myostimulation for the care of inclusion body myositis-A case report.

External muscle stimulation, possibly combined with active muscle contraction, could improve physical functioning and performance in inclusion body myositis. Inclusion body myositis (IBM) is a chronic, progressive inflammatory muscle disease with largely unknown causes. It typically affects men more than women, usually beginning in the latter half of life. IBM leads to muscle weakness and wasting, especially in the arms and legs, which significantly impairs daily functioning and complicates participation in exercise training. Few studies have examined the impact of physical training on fitness, inflammation markers, and quality of life in IBM patients. The patient, a Caucasian male (78.3 kg, 174.0 cm, born October 1948), was diagnosed with IBM in October 2011. From October 2017 to September 2019, he underwent exercise training focused on external muscle stimulation combined with active muscle contractions. Regular assessments included cardiopulmonary exercise testing, functional tests (6-min walking test, modified timed up and go test, modified chair rise test), lung function exams, blood parameters, body composition, and quality of life questionnaires. The decline in physical fitness may have been slowed during the intervention period, as indicated by some improvements like peak oxygen uptake and the functional test results while other parameters remained unchanged or declined like peak power output, fat-free mass or lung functioning. However, a recurrence of his prostate cancer after treatment with androgen deprivation therapy may have led to further declines and thus increased muscle wasting. The data may suggest that supportive exercise programs focusing on external muscle stimulation, possibly combined with active muscle contraction, might improve physical functioning, exercise performance, and quality of life in IBM management.

A mathematical model of Cheyne-Stokes or periodic breathing

Cheyne-Stokes Breathing is a periodic cycle of apnea followed by hyperventilation. A theory of this phenomenon is developed based on a minimal set of physiological assumptions. The rate of loss of CO2 from venous blood is proportional to the CO2 concentration in the lungs times the respiration rate; the respiration rate is a linear function of arterial CO2 concentration above a threshold, and zero below that threshold. A time delay between blood in lungs and respiratory response allows the system to go into oscillation. These assumptions lead to a single nonanalytic delay-differential equation containing only three parameters, which we call respiratory recovery coefficients, (α,β,γ). A detailed study of the solutions to this equation is presented here. For β below a first threshold, breathing becomes steady, and any disturbance recovers exponentially to the steady state (∼overdamped oscillator). Above the first threshold, breathing recovers to the steady state by decaying oscillations (∼underdamped oscillator). Above a second threshold, oscillations grow to reach a limit cycle, and when that cycle is sufficiently large, it represents the Cheyne-Stokes cycle of hyperventilation and apnea. Fourier analysis shows that the transition to growing oscillations is a forward or soft Hopf bifurcation. In the Cheyne-Stokes region (sufficiently large β), the equation predicts the shapes of the curves representing the time-dependence of arterial CO2 and the respiration rate. From these shapes, we infer the values of the respiratory recovery coefficients for several groups of patients. With additional approximations, we infer the values of other physiological parameters, including cardiac output, CO2 chemosensitivity, and volume of blood between lungs and detectors.

The impact of tangeretin combined with whey protein on exercise-induced bronchoconstriction in professional athletes: a placebo-controlled trial.

Exercise-induced bronchoconstriction (EIB) is highly prevalent in athletes. The objective of this study was to assess the therapeutic efficacy of daily tangeretin combined with whey protein supplementation over a period of 4weeks in professional athletes with EIB. Using a placebo-controlled, double-blind, paired, randomized trial design, a cohort of 30 professional athletes with EIB, consisting of 14 females and 16 males, was divided into two groups: the tangeretin combined with whey protein intervention group (TIG), and the placebo control group (PCG). Both the TIG and PCG underwent exercise challenge tests (ECT) and VO2max tests before (ECT1, V1) and after (ECT2, V2) the intervention. Blood (eosinophils, neutrophils, and basophils) and serum (interleukin-5, IL-5; interleukin-8, IL-8; Clara cell secretory protein-16, CC16; immunoglobulin E, IgE) levels were measured early in the morning of ECT1 and ECT2, respectively. Lung function was assessed immediately before and post-ECT immediately. Tangeretin combined with whey protein use for 4 weeks attenuated the decrease in forced expiratory volume in 1 s (FEV1) post trials (∆FEV1(ECT1-ECT2): mean (SD) TIG -7.51(6.9)% vs. PCG -2.33(11.49)%, p = 0.013). Tangeretin also substantially attenuated IL-5 concentration (∆IL-5(T1-T5): Tangeretin -19.4% vs Placebo + 8.37%, p = 0.022); IL-8 concentration (∆IL-8(T1-T5): Tangeretin -17.28% vs Placebo + 6.1%, p = 0.012); CC16 concentration (∆CC16(T1-T5): Tangeretin -11.77% vs Placebo + 24.19%); and IgE concentration in the serum (∆IgE(T1-T5): Tangeretin -24.1% vs Placebo -3.9%), and significantly decreased neutrophil count (∆N(T1-T5): Tangeretin -11.34% vs Placebo + 0.3%) and eosinophil count in blood (∆N(T1-T5): Tangeretin -38.5% vs Placebo + 4.35%). Compared with V1, VO2max (p = 0.042) and TLim (p = 0.05) of V2 were significantly increased in the TIG, and there was no significant change in the PCG. Meanwhile, six athletes in the TIG and 0 athletes in the PCG became EIB-negative at ECT2; the overall negative conversion rate of EIB was 40.00% in TCG. Additionally, the number of cough symptoms decreased from 9 to 3 and dyspnea from 4 to 2 in the TIG. After high-intensity exercise, athletes with EIB achieved significant improvements in lung function and blood inflammatory factors by combining tangeretin and whey protein supplementation. EIB athletes also showed longer exercise endurance and VO2max at 4 weeks after TI. In addition, some patient symptoms disappeared after combination supplementation. The effect of this treatment on professional athletes with EIB was beneficial.

On-demand imidazolidinyl urea-based tissue-like, self-healable, and antibacterial hydrogels for infectious wound care

Bacterial wound infections are a growing challenge in healthcare, posing severe risks like systemic infection, organ failure, and sepsis, with projections predicting over 10 million deaths annually by 2050. Antibacterial hydrogels, with adaptable extracellular matrix-like features, are emerging as promising solutions for treating infectious wounds. However, the antibacterial properties of most of these hydrogels are largely attributed to extrinsic agents, and their mechanisms of action remain poorly understood. Herein we introduce for the first time, modified imidazolidinyl urea (IU) as the polymeric backbone for developing tissue-like antibacterial hydrogels. As-designed hydrogels behave tissue-like mechanical features, outstanding antifreeze behavior, and rapid self-healing capabilities. Molecular dynamics (MD) simulation and density functional theory (DFT) calculation were employed to well-understand the extent of H-bonding and metal-ligand coordination to finetune hydrogels’ properties. In vitro studies suggest good biocompatibility of hydrogels against mouse fibroblasts & human skin, lung, and red blood cells, with potential wound healing capacity. Additionally, the hydrogels exhibit good 3D printability and remarkable antibacterial activity, attributed to concentration dependent ROS generation, oxidative stress induction, and subsequent disruption of bacterial membrane. On top of that, in vitro biofilm studies confirmed that developed hydrogels are effective in preventing biofilm formation. Therefore, these tissue-mimetic hydrogels present a promising and effective platform for accelerating wound healing while simultaneously controlling bacterial infections, offering hope for the future of wound care.

The Role of Mast Cells in the Remodeling Effects of Molecular Hydrogen on the Lung Local Tissue Microenvironment under Simulated Pulmonary Hypertension

Molecular hydrogen (H2) has antioxidant, anti-inflammatory, and anti-fibrotic effects. In a rat model simulating pulmonary fibrotic changes induced by monocrotaline-induced pulmonary hypertension (MPH), we had previously explored the impact of inhaled H2 on lung inflammation and blood pressure. In this study, we further focused the biological effects of H2 on mast cells (MCs) and the parameters of the fibrotic phenotype of the local tissue microenvironment. MPH resulted in a significantly increased number of MCs in both the pneumatic and respiratory parts of the lungs, an increased number of tryptase-positive MCs with increased expression of TGF-β, activated interaction with immunocompetent cells (macrophages and plasma cells) and fibroblasts, and increased MC colocalization with a fibrous component of the extracellular matrix of connective tissue. The alteration in the properties of the MC population occurred together with intensified collagen fibrillogenesis and an increase in the integral volume of collagen and elastic fibers of the extracellular matrix of the pulmonary connective tissue. The exposure of H2 together with monocrotaline (MCT), despite individual differences between animals, tended to decrease the intrapulmonary MC population and the severity of the fibrotic phenotype of the local tissue microenvironment compared to changes in animals exposed to the MCT effect alone. In addition, the activity of collagen fibrillogenesis associated with MCs and the expression of TGF-β and tryptase in MCs decreased, accompanied by a reduction in the absolute and relative content of reticular and elastic fibers in the lung stroma. Thus, with MCT exposure, inhaled H2 has antifibrotic effects involving MCs in the lungs of rats. This reveals the unknown development mechanisms of the biological effects of H2 on the remodeling features of the extracellular matrix under inflammatory background conditions of the tissue microenvironment.

A pilot study of thecardiopulmonary effects in healthy volunteers after exposure to high levels of PM2.5 in a New York City subway station.

Subway systems are becoming increasingly common worldwide transporting large populations in major cities. PM2.5 concentrations have been demonstrated to be exceptionally high when underground, however. Studies on the impact of subway PM exposure on cardiopulmonary health in the United States are limited. Healthy volunteers in New York City were exposed to a 2-h visit on the 9th Street Station platform on the Port Authority Trans-Hudson train system. Blood pressure, heart rate variability (HRV), spirometry, and forced impulse oscillometry were measured, and urine, blood spot, and nasal swab biosamples were collected for cytokine analysis at the end of the 2-h exposure period. These endpoints were compared against individual control measurements collected after 2-h in a "clean" control space. In addition to paired comparisons, mixed effects models with subject as a random effect were employed to investigate the effect of the PM2.5 concentrations and visit type (i.e., subway vs. control). Mean PM2.5 concentrations on the platform and during the control visit were 293.6 ± 65.7 (SD) and 4.6 ± 1.9µg/m3, respectively. There was no change in any of the health metrics, but there was a non-significant trend for SDNN to be lower after subway exposure compared to control exposure. Total symptomatic scores did increase post-subway exposure compared to reported values prior to exposure or after the control visit. No significant changes in cytokine concentrations in any specimen type were observed. Mixed-effects models mostly corroborated these paired comparisons. Acute exposures to PM on a subway platform do not cause measurable cardiopulmonary effects apart from reductions in HRV and increases in symptoms in healthy volunteers. These findings match other studies that found little to no changes in lung function and blood pressure after exposure in underground subway stations. Future work should still target potentially more vulnerable populations, such as individuals with asthma or those who spend increased time underground on the subway such as transit workers.

Lung function and blood gas of rats after different protocols of hypobaric exposure.

High-altitude pulmonary edema (HAPE) is a common disease observed in climbers, skiers and soldiers who ascend to high altitudes without previous acclimatization. Thus, a reliable and reproducible animal model that can mimic the mechanisms of pathophysiologic response in humans is crucial for successful investigations. Our results showed that exposure to 4500 m for 2 days had little influence on lung function or blood gas, and exposure to 6000 m for 2 or 3 days could change lung function and blood gas, but most parameters returned to nearly normal levels within 48 hours. This study indicates that exposure to 6000 m for 3 days may induce evident lung edema and significantly alter lung function and blood gas, which may mimic HAPE in clinical practice. Thus, this animal model of HAPE may be used in future studies on HAPE.

Activation of the AMPK/Nrf2 pathway ameliorates LPS-induced acute lung injury by inhibiting oxidative stress and reducing inflammation

BackgroundNumerous diseases-related acute lung injury (ALI) contributed to high mortality. Currently, the therapeutic effect of ALI was still poor. The detailed mechanism of ALI remained elusive and this study aimed to elucidate the mechanism of ALI.MethodThis study was performed to expose the molecular mechanisms of AMPK/Nrf2 pathway regulating oxidative stress in LPS-induced AMI mice. The mouse ALI model was established via intraperitoneal injection of LPS, then the lung tissue and blood samples were obtained, followed by injection with Dimethyl fumarate (DMF). Finally, Western blot, HE staining, injury score, lung wet/dry ratio, reactive oxygen species (ROS) and ELISA were used to elucidate the mechanism of AMPK/Nrf2 pathway in LPS -induced acute lung injury by mediating oxidative stress.ResultsThe lung tissue injury score was evaluated, showing higher scores in the model group compared to the AMPK activator and control groups. DCFH-DA indicated that LPS increased ROS production, while AMPK activator DMF reduced it, with the model group exhibiting higher ROS levels than the control and AMPK activator groups. The lung wet/dry ratio was also higher in the model group. Western blot analysis revealed LPS reduced AMPK and Nrf2 protein levels, but DMF reversed this effect. ELISA results showed elevated IL-6 and IL-1β levels in the model group compared to the AMPK activator and control groups.Conclusion:ConclusionActivating the AMPK/Nrf2 pathway can improve LPS-induced acute lung injury by down-regulation of the oxidative stress and corresponding inflammatory factor level.

Blood cadmium concentration and pulmonary function injury: potential mediating role of oxidative stress in chronic obstructive pulmonary disease patients

BackgroundExposure to cadmium (Cd) is associated with a reduction in lung function among patients with chronic obstructive pulmonary disease (COPD). The longitudinal relationship and mechanism underlying the link between Cd exposure and lung function changes among COPD patients are yet unknown.MethodsThe cohort study included 259 eligible patients who underwent regular professional follow-ups. Blood Cd levels and serum 8-iso-prostaglandin F2 alpha (8-iso-PGF2α) levels were assessed. Lung function was determined at baseline and follow-up research. The associations between changes in lung function and blood Cd concentration were analysed using multivariate linear and logistic regression models.ResultsEach 1-ppb elevation in blood Cd content resulted in a 0.420 L decrease in forced vital capacity (FVC), a 0.424 L decrease in forced expiratory volume in 1 s (FEV1), a 4.341% decrease in FEV1/FVC%, and a 8.418% decrease in FEV1% predicted in patients with COPD. Blood Cd concentration showed a positive correlation with serum 8-iso-PGF2α levels in a specific range. The relative contribution of increased serum levels of 8-iso-PGF2α to Cd-induced declines in FEV1, predicted FEV1%, and FEV1/FVC% were 2.08%, 8.08%, and 13.19%, respectively.ConclusionBlood Cd levels are associated with lung function changes in COPD patients. Oxidative stress is thought to be an important mediator in Cd-induced reduction of pulmonary function.

Structured adaptive boosting trees for detection of multicellular aggregates in fluorescence intravital microscopy

Fluorescence intravital microscopy captures large data sets of dynamic multicellular interactions within various organs such as the lungs, liver, and brain of living subjects. In medical imaging, edge detection is used to accurately identify and delineate important structures and boundaries inside the images. To improve edge sharpness, edge detection frequently requires the inclusion of low-level features. Herein, a machine learning approach is needed to automate the edge detection of multicellular aggregates of distinctly labeled blood cells within the microcirculation. In this work, the Structured Adaptive Boosting Trees algorithm (AdaBoost.S) is proposed as a contribution to overcome some of the edge detection challenges related to medical images. Algorithm design is based on the observation that edges over an image mask often exhibit special structures and are interdependent. Such structures can be predicted using the features extracted from a bigger image patch that covers the image edge mask. The proposed AdaBoost.S is applied to detect multicellular aggregates within blood vessels from the fluorescence lung intravital images of mice exposed to e-cigarette vapor. The predictive capabilities of this approach for detecting platelet-neutrophil aggregates within the lung blood vessels are evaluated against three conventional machine learning algorithms: Random Forest, XGBoost and Decision Tree. AdaBoost.S exhibits a mean recall, F-score, and precision of 0.81, 0.79, and 0.78, respectively. Compared to all three existing algorithms, AdaBoost.S has statistically better performance for recall and F-score. Although AdaBoost.S does not outperform Random Forest in precision, it remains superior to the XGBoost and Decision Tree algorithms. The proposed AdaBoost.S is widely applicable to analysis of other fluorescence intravital microscopy applications including cancer, infection, and cardiovascular disease.

IL-35 promotes IL-35+IL-10+ Bregs and Conventional LAG3+ Tregs in the lung tissue of OVA-Induced Asthmatic Mice.

This study aimed to investigate the effect of interleukin-35 (IL-35) on inflamed lung tissue in a murine model of asthma. IL-35 was examined for its potential to induce regulatory lymphocytes during ovalbumin (OVA)-induced acute lung injury. Female BALB/c mice sensitized with OVA and were treated with recombinant IL-35 (rIL-35) via intranasal or intraperitoneal routes and were administered 4h before OVA challenge. The effects of rIL-35 treatment on the lung and blood levels of regulatory B cells (Bregs) and regulatory T cells (Tregs), as well as their production of immunosuppressive cytokines, were determined using flow cytometry and enzyme-linked immunosorbent assay (ELISA), respectively. Treatment of OVA-sensitized asthmatic mice with rIL-35, whether administered intranasally or intraperitoneally, resulted in reduced lung inflammation and injury. This reduction was accompanied by an increase in the frequency of IL-35 producing Bregs, IL-35 and IL-10 producing Bregs, and conventional LAG3+ Tregs in the lung tissues and blood. This increase was more pronounced with intranasal rIL-35. Furthermore, there was a positive correlation between the levels of these regulatory cells and lung gene expression of IL-35 and IL-10, and an inverse correlation with both lung gene expression and plasma level of IL-17. The results of this study suggest that IL-35, through its ability to increase Bregs and Tregs, is effective in reversing lung inflammation in the context of asthma. Since the increase was more pronounced with intranasal administration, this highlights the therapeutic potential of its local intrapulmonary application in managing asthma-related inflammation.

Identification and role of differentially expressed genes/proteins between pulmonary tuberculosis patients and controls across lung tissues and blood samples.

Differentially expressed genes/proteins (DEGs/DEPs) play critical roles in pulmonary tuberculosis (PTB) diagnosis and treatment. However, there is a scarcity of reports on DEGs/DEPs in lung tissues and blood samples in PTB patients. We aim to identify the DEGs/DEPs in lung tissues and blood samples of PTB patients and investigate their roles in PTB. The lung granulomas and normal tissues were collected from PTB patients for proteomic and transcriptomic analyses. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) analyses annotated the functions of DEGs/DEPs. The GSE107994 data set was downloaded to identify the DEGs/DEPs in peripheral blood. The common DEGs and DEPs were identified. A nomogram was established. Pearson correlation analysis was conducted. Eighty-three DEGs/DEPs were identified. These DEGs/DEPs were mainly enriched in the movement of cell or subcellular components, regulation of cellular component biogenesis, and actin filament-based process as well as in the pathways of inositol phosphate metabolism, adherens junction, phosphatidylinositol signaling system, leukocyte transendothelial migration, regulation of actin cytoskeleton, and tight junction. There were eight common DEGs/DEPs (TYMP, LAP3, ADGRL2, SIL1, LMO7, SULF 1, ANXA3, and PACSIN3) between the lung tissues and blood samples. They were effective in predicting tuberculosis. Moreover, the activated dendritic cells, macrophages, monocytes, neutrophils, and regulatory T cells were significantly positively correlated with TYMP (r > .50), LAP3 (r > .50), SIL1 (r > .50), ANXA3 (r > .5), andPACSIN3 (r < .50), while negatively correlated with LMO7 (r < -0.50) (p < .05). ADGRL2 and SULF1 did not have a significant correlation (p > .05). The sample size was small. Eight common DEGs/DEPs of lung tissues and blood samples were identified. They were correlated with immune cells and demonstrated predictive value for PTB. Our data may facilitate the diagnosis and treatment of PTB.

Lung Transcriptomics Links Emphysema to Barrier Dysfunction and Macrophage Subpopulations.

While many studies have examined gene expression in lung tissue, the gene regulatory processes underlying emphysema are still not well understood. Finding efficient non-imaging screening methods and disease-modifying therapies has been challenging, but knowledge of the transcriptomic features of emphysema may help in this effort. Our goals were to identify emphysema-associated biological pathways through transcriptomic analysis of bulk lung tissue, to determine the lung cell types in which these emphysema-associated pathways are altered, and to detect unique and overlapping transcriptomic signatures in blood and lung samples. Using RNA-sequencing data from 446 samples in the Lung Tissue Research Consortium (LTRC) and 3,606 blood samples from the COPDGene study, we examined the transcriptomic features of chest computed tomography-quantified emphysema. We also leveraged publicly available lung single-cell RNA-sequencing data to identify cell types showing COPD-associated differential expression of the emphysema pathways found in the bulk analyses. In the bulk lung RNA-seq analysis, 1,087 differentially expressed genes and 34 dysregulated pathways were significantly associated with emphysema. We observed alternative splicing of several genes and increased activity in pluripotency and cell barrier function pathways. Lung tissue and blood samples shared differentially expressed genes and biological pathways. Multiple lung cell types displayed dysregulation of epithelial barrier function pathways, and distinct pathway activities were observed among various macrophage subpopulations. This study identified emphysema-related changes in gene expression and alternative splicing, cell-type specific dysregulated pathways, and instances of shared pathway dysregulation between blood and lung.

CircSORBS1 inhibits lung cancer progression by sponging miR-6779-5p and directly binding RUFY3 mRNA

Lung cancer is the primary cause of cancer-related death worldwide, and its global incidence and mortality rates remain high. The differential expression of circular RNAs (circRNAs) can affect the development of cancer, but the mechanisms by which circRNAs regulate lung cancer progression remain unclear. In this study, we identified circSORBS1, a circRNA that has not been previously described in lung cancer and is significantly underexpressed in lung cancer tissues, blood and cell lines, and the low expression of circSORBS1 correlated with tumour grade and prognosis. In vitro and in vivo functional experiments revealed that circSORBS1 overexpression inhibited cell proliferation and migration while enhancing apoptosis. Mechanistically, circSORBS1 acts as a sponge for miR-6779-5p, indirectly inhibiting RUFY3 mRNA degradation. Simultaneously, it binds to RUFY3 mRNA to enhance its stability. This dual regulatory mechanism leads to an increase in RUFY3 protein levels, which ultimately activates the YWHAE/BAD/BCL2 apoptotic signalling pathway and suppresses lung cancer progression. Our findings not only increase the knowledge about the regulatory pattern of circRNA expression but also provide new insights into the mechanisms by which circRNAs regulate lung cancer development.

Impact of resistance exercise program on muscle strength, cardiopulmonary function and glycolipid metabolism of bedridden population aged 80 years and above: A randomized controlled trial.

This study aimed to evaluate the impact of a resistance exercise program in the bedridden older adults in China. The patients aged 80 years and above with stable diseases were randomly divided into control group (receiving routine treatment and nursing) and training group (receiving the elastic ball and elastic band training applied for 55 minutes, 3 times a week during 6 months). A total of 59 patients (control group: 30; training groups: 29) completed the study. In terms of muscle strength, the patients of the training group had better grip strength and supine leg lifts and 30-s sit-to-stand actions. In terms of cardiopulmonary function and glycolipid metabolism, the patients in the training groups had better lung capacity and high-density lipoprotein. The low-load and low-intensity resistance training may effectively improve not only the muscle strength of the bedridden older adults, but also the lung function and blood lipid metabolism.

Anthrahydroquinone‑2,6‑disulfonate attenuates PQ‑induced acute lung injury through decreasing pulmonary microvascular permeability via inhibition of the PI3K/AKT/eNOS pathway.

In paraquat (PQ)‑induced acute lung injury (ALI)/ acute respiratory distress syndrome, PQ disrupts endothelial cell function and vascular integrity, which leads to increased pulmonary leakage. Anthrahydroquinone‑2,6‑disulfonate (AH2QDS) is a reducing agent that attenuates the extent of renal injury and improves survival in PQ‑intoxicated Sprague‑Dawley (SD) rats. The present study aimed to explore the beneficial role of AH2QDS in PQ‑induced ALI and its related mechanisms. A PQ‑intoxicated ALI model was established using PQ gavage in SD rats. Human pulmonary microvascular endothelial cells (HPMECs) were challenged with PQ. Superoxide dismutase, malondialdehyde, reactive oxygen species and nitric oxide (NO) fluorescence were examined to detect the level of oxidative stress in HPMECs. The levels of TNF‑α, IL‑1β and IL‑6 were assessed using an ELISA. Transwell and Cell Counting Kit‑8 assays were performed to detect the migration and proliferation of the cells. The pathological changes in lung tissues and blood vessels were examined by haematoxylin and eosin staining. Evans blue staining was used to detect pulmonary microvascular permeability. Western blotting was performed to detect target protein levels. Immunofluorescence and immunohistochemical staining were used to detect the expression levels of target proteins in HPMECs and lung tissues. AH2QDS inhibited inflammatory responses in lung tissues and HPMECs, and promoted the proliferation and migration of HPMECs. In addition, AH2QDS reduced pulmonary microvascular permeability by upregulating the levels of vascular endothelial‑cadherin, zonula occludens‑1 and CD31, thereby attenuating pathological changes in the lungs in rats. Finally, these effects may be related to the suppression of the phosphatidylinositol‑3‑kinase (PI3K)/protein kinase B (AKT)/endothelial‑type NO synthase (eNOS) signalling pathway in endothelial cells. In conclusion, AH2QDS ameliorated PQ‑induced ALI by improving alveolar endothelial barrier disruption via modulation of the PI3K/AKT/eNOS signalling pathway, which may be an effective candidate for the treatment of PQ‑induced ALI.

Applying machine learning to construct an association model for lung cancer and environmental hormone high-risk factors and nursing assessment reconstruction.

To utilize machine learning techniques to develop an association model linking lung cancer and environmental hormones to enhance the understanding of potential lung cancer risk factors and refine current nursing assessments for lung cancer. This study is exploratory in nature. In Stage 1, data were sourced from a biological database, and machine learning methods, including logistic regression and neural-like networks, were employed to construct an association model. Results indicate significant associations between lung cancer and blood cadmium, urine cadmium, urine cadmium/creatinine, and di(2-ethylhexyl) phthalate. In Stage 2, 128 lung adenocarcinoma patients were recruited through convenience sampling, and the model was validated using a questionnaire assessing daily living habits and exposure to environmental hormones. Analysis reveals correlations between the living habits of patients with lung adenocarcinoma and exposure to blood cadmium, urine cadmium, urine cadmium/creatinine, polyaromatic hydrocarbons, diethyl phthalate, and di(2-ethylhexyl) phthalate. According to the World Health Organization's global statistics, lung cancer claims approximately 1.8 million lives annually, with more than 50% of patients having no history of smoking or non-traditional risk factors. Environmental hormones have garnered significant attention in recent years in pathogen exploration. However, current nursing assessments for lung cancer risk have not incorporated environmental hormone-related factors. This study proposes reconstructing existing lung cancer nursing assessments with a comprehensive evaluation of lung cancer risks. The findings underscore the importance of future studies advocating for public screening of environmental hormone toxins to increase the sample size and validate the model externally. The developed association model lays the groundwork for advancing cancer risk nursing assessments.