Yu Jiang

A growing body of evidence suggests that enhanced glycolysis profoundly reprograms inflammatory response in acute lung injury (ALI)/ acute respiratory dist

Background: The diffusing capacity of the lung for carbon monoxide (DLCO) is a key measure of alveolar–capillary gas exchange, but its clinical significance in chronic obstructive pulmonary disease (COPD) remains incompletely defined. This study aimed to characterize the demographic, clinical, functional, and comorbid profiles of COPD patients stratified by the degree of DLCO impairment, and to evaluate the potential value of DLCO as a marker for disease severity and clinical phenotyping in a Chinese cohort. Methods: This single-center retrospective cross-sectional study enrolled 650 patients diagnosed with COPD (according to GOLD 2025 criteria) who underwent pulmonary function tests between January 2024 and February 2025 at the university-town hospital of Chongqing Medical University. Patients were stratified by predicted DLCO% into four groups: normal (≥80%), mild impairment (60–79%), moderate impairment (40–59%), and severe impairment (p = 0.018), older age (67.3 ± 9.0 to 72.9 ± 6.7 years, p < 0.001), lower BMI (median from 23.9 to 20.0 kg/m², p < 0.001), and higher smoking prevalence (58.7% to 87.5%, p = 0.001). The prevalence of pulmonary tuberculosis rose markedly (0.58% to 9.09%, p = 0.037). All spirometric parameters declined (e.g., FEV1%pred from 67.3% to 32.6%, p < 0.001). Systemic inflammatory markers (NLR, SII) increased, while hemoglobin and albumin decreased (both p < 0.001). Respiratory failure occurred in 30.0% of the severe DLCO group (predominantly type I, p p = 0.012) and a trend toward higher pulmonary hypertension risk (27.8%, p = 0.056). DLCO%pred correlated positively with FEV1%pred (r = 0.394, p < 0.001) and oxygen saturation (r = 0.151, p < 0.001), and negatively with NLR (r = −0.165, p < 0.001) and SII (r = −0.149, p < 0.001). Conclusions: In COPD, DLCO impairment is associated with distinct clinical phenotypes, including male sex, advanced age, malnutrition, increased tuberculosis risk, worse lung function, systemic inflammation, and respiratory/cardiac dysfunction. These findings support DLCO as a valuable complementary marker for disease severity characterization in COPD. Longitudinal studies are needed to confirm its prognostic value.

A CRISPR/Cas9-regulated dual-ring topological allosteric probe was developed for ultrasensitive and specific detection of the EGFR L858R mutation, where the released reporter ring triggers RCA and fluorescent probe hybridization for signal readout.

Background: Sepsis outcomes remain difficult to predict because immune trajectories are heterogeneous and dynamically shift from early activation to immunosuppression. Endotoxin tolerance (ET) in circulating monocytes/macrophages is a key mechanism of sepsis-associated immunosuppression but has not been systematically leveraged for prognostication. We sought to develop and clinically validate an ET-related gene (ETG) signature for short-term mortality risk stratification. Method: Public whole-blood transcriptomic datasets were intersected with curated ET gene sets to derive ETG candidates. An ensemble machine-learning framework (108 model/feature-selection combinations across 12 algorithms) was used to build and rank prognostic models for 28-day mortality; the final parsimonious signature (10 ETGs, including IL4R, ATM, CX3CR1, FCGR1A) informed a risk score. A two-variable nomogram (age + ETG risk score) was constructed. Internal performance was assessed by bootstrapped calibration, time-dependent ROC/AUC at 7, 14, and 28 days, and Harrell’s C-index. Experimental validation used a prospective ICU cohort (n=50; 13 survivors, 37 non-survivors). PBMCs were profiled by RT-qPCR and Western blot; CD14 ⁺ monocytes were analyzed by flow cytometry for FCGR1A/CD64, CX3CR1, and PD-1. We further explored regulatory context (ceRNA network) and druggability (DGIdb query and molecular docking to CX3CR1, FCGR1A, and TLR5). Results: The 10-gene ETG signature stratified mortality risk with acceptable discrimination and calibration. AUCs were 0.76 (95% CI 0.69–0.83), 0.78 (0.72–0.83), and 0.73 (0.67–0.78) at 7, 14, and 28 days, respectively; Harrell’s C-index was 0.782. The age-integrated nomogram showed close agreement between predicted and observed survival across timepoints. Functional enrichment indicated immune-response pathways enriched in the low-risk group. In the clinical cohort, non-survivors exhibited lower mRNA and protein levels of FCGR1A, TLR5, and CX3CR1 in PBMCs; flow cytometry revealed reduced proportions of FCGR1A ⁺ , CX3CR1 ⁺ , and PD-1 ⁺ CD14 ⁺ monocytes (p<0.01). The ceRNA analysis highlighted a putative NEAT1/miR-1287-5p/CX3CR1 axis. Docking suggested plausible ligandability of CX3CR1, FCGR1A, and TLR5, nominating candidates such as valproic acid and CGP-52608 for follow-up testing. Conclusion: An ET-anchored, 10-gene signature captures a clinically relevant axis of sepsis-associated immunosuppression and enables short-term mortality risk stratification. Integration with age yields a simple nomogram with stable internal performance. Multilayer validation (transcript, protein, single-cell) supports biological plausibility. Prospective multicenter studies with richer clinical annotation and functional assays are warranted to confirm generalizability and to evaluate ET-guided immunomodulatory strategies.

DNA damage and repair (DDR) is involved in the antitumor immune response, however, the correlation between DNA damage response with immunotherapy in NSCLC remain unclear. We examined the relationship between DDR alterations and expression of PD-L1 in non-small cell lung cancer. Tumor tissues, para-carcinoma and normal tissues, were obtained from 54 patients who were surgically resected NSCLC tumors. Patient characteristics, neoplasm staging and pathological information were collected. Immunohistochemical analysis of tissue samples was analyzed for γH2AX、RAD51, PARP-1 and PD-L1 protein expression. A total of 54 patients with non-small cell lung cancer were included in this study, including 24 males and 30 females with ages ranging from 45 to 79 years (mean, 63.5 years). The high expression rate of γH2AX staining in lung cancer was 81.5%(44/54)and the expression levels of γH2AX protein were significantly higher in NSCLC than those in paired para-carcinoma 50%(27/54) and normal tissues 42.6%(23/54). The expression levels of RAD51 protein were significantly higher in lung cancer tissue 68.5%(37/54) than those in paired para-carcinoma 48.1%(26/54) and normal tissues 40.7%(22/54). There was a significant correlation between high RAD51 expression and male patients 87.5%(21/24) (p = 0.009) and a history of smoking 90%(18/20) (p = 0.014). The presence of any DDR alteration was showed with PD-L1. (1) HigherγH2AX expression was observed in the PD-L1 positive cases 90.6% (29/32) compared to the PD-L1 negative cases 68.2% (15/22). Lung cancers with higher γH2AX expression were associated with the higher expression of PD-L1 (p = 0.046, r = 0.284). (2) There was no statistically significant correlation between expression of PD-L1 and RAD51 (p = 0.221, r = 0.168). (3) Higher PARP-1 expression was observed in the PD-L1 negative cases 59.1% (13/22) compared to the PD-L1 positive cases 25% (8/32). Lung cancers with higher PARP-1 expression were associated with the lower expression of PD-L1 (p = 0.009, r=-0.344). (4) No statistically significant association was observed in relationship between expression of DDR Expression (γH2AX、RAD51) and PARP-1 of patients (p = 0.507 and p = 0.817,respectively). Overall, our study shows that high expression of γH2AX, RAD51, and PARP1 proteins display in NSCLC and proves that DNA damage repair may be closely related to the occurrence and development of NSCLC. γH2AX could be a predictor of the adaptation of ICIs as an alternative to PD-L1, and NSCLC is expected to benefit from PARP-1 inhibitors combined with immunotherapy.

Background: Acute respiratory distress syndrome (ARDS) is characterized by diffuse lung injury and high mortality rates due to severe inflammation. Adipose tissue, functioning as both an endocrine and immune organ, plays a crucial role in immune regulation by secreting a variety of adipokines. Among these, adipose tissue-derived extracellular vesicles (EVs) have emerged as novel mediators of intercellular communication, capable of delivering bioactive molecules such as microRNAs to target cells. This study aimed to elucidate the immunomodulatory roles and underlying mechanisms of adipose tissue-derived EVs in the pathogenesis of ARDS. Methods: Subcutaneous adipose tissue extracellular vesicles (SAT-EVs) were collected from the mice via ultracentrifugation. C57BL/6 mice were administered SAT-EVs (1× 10^9 particles per mouse) via tail vein injection, followed by an intraperitoneal Lipopolysaccharide (LPS) injection three hours later to induce acute respiratory distress syndrome (ARDS). The mice were euthanized after 18 h to evaluate the permeability of the microvessels and level of inflammation in the lungs. For in vitro experiments, RAW 264.7 macrophages were stimulated with LPS, with or without SAT-EVs, as a control, to evaluate the inflammatory response of the macrophages. Results: SAT-EVs treatment enhanced the survival rate of ARDS mice and reduced pulmonary vascular permeability. SAT-EVs were internalized by alveolar macrophages, leading to an attenuation of inflammation, as indicated by decreased levels of TNF-α, IL-1β, iNOS, PTGS2, and CCL2. Notably, SAT-EVs transferred miR-26a-5p to alveolar macrophages, which directly targeted conserved helix-loop-helix ubiquitous kinase (CHUK), a key regulator of the NF-κB pathway. This inhibition resulted in reduced transcription of inflammatory mediators (iNOS, PTGS2, and IL-1β). In vitro, SAT-EVs were internalized by RAW 264.7 macrophages, leading to the suppression of LPS-induced inflammation, as shown by decreased expression of TNF-α, IL-1β, iNOS, PTGS2, and CCL2. These findings suggest that miR-26a-5p plays a crucial role in the anti-inflammatory effects of SAT-EVs by suppressing CHUK and modulating the NF-κB pathway. Conclusion: SAT-EVs significantly attenuated LPS-induced ARDS, potentially through the CHUK/NF-κB pathway mediated by miR-26a-5p, thereby exerting protective effects against inflammatory lung injury. These findings provide mechanistic insights into the role of SAT-EVs in immune modulation and suggest their potential as a therapeutic strategy for ARDS.

Linoleic acid (LA), an essential fatty acid, has emerged as a pivotal regulator in disorders associated with inflammation in recent years; however, the underlying mechanisms are still not completely understood. We utilized network pharmacology...

Introduction: Acute lung injury (ALI) is a critical and lethal medical condition. This syndrome is characterized by an imbalance in the body's oxidation stress and inflammation. Linoleic acid (LA), a polyunsaturated fatty acid, has been extensively studied for its potential health benefits, including anti‐inflammatory and antioxidant activities. However, the therapeutic effects of LA on ALI remain unexplored.Methods: Lipopolysaccharide (LPS), found in gram‐negative bacteria's outer membrane, was intraperitoneally injected to induce ALI in mice. In vitro model was established by LPS stimulation of mouse lung epithelial 12 (MLE‐12) cells.Results: LA treatment demonstrated a significant amelioration in LPS‐induced hypothermia, poor state, and pulmonary injury in mice. LA treatment resulted in a reduction in the concentration of bronchoalveolar lavage fluid (BALF) protein and an increase in myeloperoxidase (MPO) activity in LPS‐induced mice. LA treatment reduced the generation of white blood cells. LA treatment reduced cell‐free (cfDNA) release and promote adenosine triphosphate (ATP) production. LA increased the levels of superoxide dismutase (SOD) and glutathione (GSH) but decreased the production of malondialdehyde (MDA). LA treatment enhanced mitochondrial membrane potential. LA attenuated LPS‐induced elevations of inflammatory cytokines in both mice and cells. Additionally, LA exerted its protective effect against LPS‐induced damage through activation of the peroxisome proliferator‐activated receptor γ coactivator l alpha (PGC‐1α)/nuclear respiratory factor 1 (NRF1)/transcription factor A of the mitochondrion (TFAM) pathway.Conclusion: LA may reduce inflammation and stimulate mitochondrial biogenesis in ALI mice and MLE‐12 cells.

There are many epidemiological pieces of evidence that show combined pulmonary fibrosis and emphysema (CPFE) patients have an increased risk of lung cancer. We conducted a systematic review of all published data to define the characteristics and treatments of lung cancer that develops in CPFE by performing a meta-analysis. Databases including PubMed, Medline and Web of Science (updated to July, 2021) were searched to find original articles that related to lung cancer in CPFE(CPFE-LC) patients and a meta-analysis was used to analyze the included 15 articles. Stata17.0 software was performed for this meta-analysis. Fifteen original studies that assessed 5933 patients were included in this meta-analysis. In the pooled data, people with CPFE-LC were elderly (70.58 years) and heavy smokers (0.959, 45.793 pack-years), with a male predominance (0.959). Most lung cancer in CPFE was located in the lower lobe (0.533) and obvious areas of pulmonary fibrosis (0.516). The highest prevalence of cellular subtypes of lung cancer in CPFE was squamous carcinoma (SqCC, 0.437) and chemotherapy was the primary treatment (0.387). The mortality rate was 0.720(95%CI: 0.657-0.783) and the 5-year survival rate was 0.250 (95%CI: 0.133-0.368). The main cause of death was infection (0.268) and respiratory failure was the main cause of death after surgery (0.392). Lung cancer in CPFE, most commonly SqCC, presents in elderly heavy smokers with a male, located in the lower lobe of the lung and the areas of fibrosis predominance. Chemotherapy is the primary treatment and the optimal treatment remains to be explored.

Background Since there is a limited ability to identify the need for intubation in the ICU, the objective of this study was to develop and validate an interpretable machine learning (ML) model to predict the need for intubation in ICU patients. Methods Seven widely used ML algorithms were applied to develop and validate prediction models. Adult patients from the Medical Information Mart for Intensive Care IV database who stayed in the ICU for longer than 24 hours were involved in developing the model. The model was then externally validated in the eICU-CRD database. In addition, the SHapley Additive exPlanations (SHAP) method was employed to illustrate the effects of the individual features attributed to the prediction model. Results A total of 11988 patients were included in the final cohort for this study. Among the seven constructed models, the CatBoost model achieved the best performance (AUC: 0.863). In the external validation, the efficacy of our model was also observed (AUC: 0.722). The Glasgow Coma Scale (GCS), body mass index (BMI), arterial partial pressure of oxygen (PaO₂) and respiratory rate (RR) were the top 4 features of the CatBoost model with the greatest impact. Conclusions We have demonstrated the potential of machine-learning approaches for predicting the need for intubation in ICU patients. The SHAP method could improve the interpretability of machine-learning models and help clinicians better understand the reasoning behind the outcome. Trial registration: Not applicable.