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Abstract Background Primary thymic adenocarcinoma (PTAC) is an extremely rare disease with a poor prognosis. In the present study, we sought to analyze the clinical characteristics and prognostic factors of patients with PTAC. Methods A total of 14 patients with PTAC treated at our center from January 2000 to January 2019 were included in this study. We retrospectively collected information on sex, age, history of smoking, family history of cancer, comorbidities, symptoms, imaging tests, serum tumor marker levels, tumor, node, metastasis (TNM) staging, and treatment records. Follow‐up information was obtained by telephone interviews or outpatient clinic visit. Univariate and multivariate Cox regression analyses were performed to investigate the clinicopathological factors associated with survival. Results Among 14 patients with PTAC, there were five males and nine females, with an average age of 48.7 ± 9.3 years. A total of 23.1% of the patients had a history of smoking. The clinical symptoms of the patients were nonspecific and seven patients had elevated levels of serum tumor markers. Surgery was performed for nine patients, among which only four received R0 resection. The median survival time of the 14 patients was 16.0 months, and the 1‐, 3‐ and 5‐year survival rates were 57.1%, 35.7% and 21.4%, respectively. TNM stage was identified as an independent prognostic factor for PTAC patients (the median survival time of stage I–IIIA vs. stage IV was 44.0 months vs. 9.0 months, p = 0.002). Conclusions PTAC is highly aggressive malignancy with poor prognosis. Surgical treatment is feasible, but R0 resection is challenging. TNM staging is significantly associated with patient survival.

Abstract Background The goal of the research was to examine the value of peripheral blood indicators in forecasting survival and recurrence among people suffering central‐type non‐small cell lung cancer (NSCLC) undergoing sleeve lobectomy (SL). Methods Clinical information was gathered from 146 individuals suffering from NSCLC who had SL at our facility between January 2014 and May 2023. Peripheral blood neutrophil lymphocyte ratio (NLR), monocyte lymphocyte ratio (MLR), and platelet lymphocyte ratio (PLR) levels were determined by receiver operating characteristic (ROC) curve to establish the threshold points. Kaplan–Meier survival analysis was employed to evaluate the prognostic value of different groupings, and both univariate and multivariate Cox proportional hazards model (referred to as COX) were performed. Results The disease‐free survival (DFS) and overall survival (OS) cutoff values were carried out via ROC analysis. Kaplan–Meier survival analysis revealed notable differences in OS for NLR (≥2.196 vs.

Remanufacturing is regarded as a sustainable manufacturing paradigm of energy conservation and environment protection. To improve the efficiency of the remanufacturing process, this work investigates an integrated scheduling problem for disassembly and reprocessing in a remanufacturing process, where product structures and uncertainty are taken into account. First, a stochastic programming model is developed to minimize the maximum completion time (makespan). Second, a Q-learning based hybrid meta-heuristic (Q-HMH) is specially devised. In each iteration, a Q-learning method is employed to adaptively choose a premium algorithm from four candidate ones, including genetic algorithm (GA), artificial bee colony (ABC), shuffled frog-leaping algorithm (SFLA), and simulated annealing (SA) methods. At last, simulation experiments are carried out by using sixteen instances with different scales, and three state-of-the-art algorithms in literature and an exact solver CPLEX are chosen for comparisons. By analyzing the results with the average relative percentage deviation (RPD) metric, we find that Q-HMH outperforms its rivals by 9.79%−26.76%. The results and comparisons verify the excellent competitiveness of Q-HMH for solving the concerned problems.

With the improvement of economic level, a continuous rise in building energy consumption brings about serious environmental problems. Therefore, this study proposes a passive energy-consuming residential building envelope thermal insulation and heat preservation method based on building information modeling technology for building energy consumption increasing and envelope structure's performance improving. Firstly, it is a study on the passive low-energy residential building envelope's thermal insulation materials and architecture, and secondly, it is a study on the improvement of the thermal insulation and heat preservation performance of the passive low-energy residential building envelope on the foundation of building information modeling. These experimental results show that in the residential building, the indoor temperature averages around 27.8 °C, of which the highest indoor ambient temperature is found at 21 o'clock, with a temperature value of 28.4 °C, which reduces 2.1 °C when comparing with the indoor temperature under the traditional residential building. Under the exterior wall construction utilizing this technology, the temperature change of the indoor environment is smoother, which satisfies people's requirements for the indoor living environment. At the same time, the area parameters of the ventilation area of the building and the area of the envelope obtained after the analysis of BIM technology have a significant effect on the cooling of the interior. This method reduces the use of resources and lays a good foundation for the further development of building informatization, which is significant in realizing the informatization developing in construction.

Although most source apportionments of VOCs use mixing ratios, about 23 % of published studies use mass concentrations. Thus, systematically exploring the changes in VOC source apportioned results caused by metric differences is important to assess the differences in key precursor apportionment results given the observed increases in O3 pollution situation. Different monitoring instruments measured hourly VOC volumetric concentrations in three typical Chinese cities (i.e., Qingdao, Shijiazhuang, and Zhumadian). Converting volumetric to mass concentrations under standard and/or actual temperature–pressure conditions, VOC values with different metrics were obtained. The impacts of different metrics on the source apportionments were then investigated. Compared to the positive matrix factorization of the volumetric data (VC-PMF), the VOC species concentrations with low relative molecular mass (RMM) in the factor profiles substantially decreased in mass data analyses (MC-PMF). However, those species with high RMM substantially increased. There were no substantial differences in the apportioned source contributions based on standard and actual condition mass concentrations. However, the high-low rankings of percent contributions apportioned using the volumetric and mass data produced substantial differences. Compared with the VC-PMF results, the percent contributions of sources dominated by species with low RMM (e.g., natural gas usage and mixed sources containing natural gas usage) apportioned by MC-PMF decreased, while those of sources that emitted high RMM species (e.g., solvent usage and mixed sources containing solvent usage) increased. Source apportionments based on the volumetric concentration data had more practical significance compared to the mass concentration data results for control strategy development since the mass data analyses created issues.

PurposeThe purpose of this retrospective study was to compare the therapeutic efficacy and safety of drug-eluting bead transarterial chemoembolization (DEB-TACE) combined with systemic therapy to systemic therapy alone as first-line treatment for unresectable patients with colorectal liver metastases (CRLM).MethodsFrom December 2017 to December 2022, patients with unresectable CRLM who received systemic therapy with or without DEB-TACE as first-line treatment were included in the study. The primary endpoint was progression-free survival (PFS). Secondary endpoints were tumor response, conversion rate and adverse events.ResultsNinety-eight patients were enrolled in this study, including 46 patients who received systemic therapy combined with DEB-TACE (DEB-TACE group) and 52 patients who received systemic therapy alone (control group). The median PFS was elevated in the DEB-TACE group compared with the control group (12.1 months vs 8.4 months, p = 0.008). The disease control rate was increased in the DEB-TACE group compared with the control group (87.0% vs 67.3%, p = 0.022). Overall response rates (39.1% vs 25.0%; p = 0.133) and conversion rate to liver resection (33.8% vs 25.0%; p = 0.290) were no different between the two groups. The multivariate analysis showed that treatment options, size of liver metastasis, number of liver metastasis, synchronous metastases, and extrahepatic metastases were independent prognostic factor of PFS. Further subgroup analyses illustrated that PFS was beneficial with the DEB-TACE group in patients with age ≥ 60, male, left colon, synchronous metastases, bilobar, number of liver metastasis > 5, extrahepatic metastases, non-extrahepatic metastases, CEA level < 5 (ng/ml), and KRAS wild-type. No grade 4 or 5 toxicities related to DEB-TACE procedures were observed.ConclusionIn patients with unresectable CRLM, systemic chemotherapy with DEB-TACE as first-line treatment may improve progression-free survival and disease control rate outcomes over systemic chemotherapy alone with manageable safety profile.

The immune response plays a pivotal role in the pathogenesis of diseases. Toll-like receptor 4 (TLR4), as an intrinsic immune receptor, exhibits widespread in vivo expression and its dysregulation significantly contributes to the onset of various diseases, encompassing cardiovascular disorders, neoplastic conditions, and inflammatory ailments. This comprehensive review centers on elucidating the architectural and distributive characteristics of TLR4, its conventional signaling pathways, and its mode of action in diverse disease contexts. Ultimately, this review aims to propose novel avenues and therapeutic targets for clinical intervention.

Abstract Heat stroke (HS) is a life-threatening systemic disease characterized by an elevated core body temperature of more than 40 ℃ and subsequent multiple organ dysfunction syndrome. With the growing frequency of global heatwaves, the incidence rate of HS has increased significantly, which has caused a huge burden on people's lives and health. Liver injury is a well-documented complication of HS and usually constitutes the direct cause of patient death. In recent years, a lot of research has been carried out on the pathogenesis and treatment strategies of HS-induced liver injury. In this review, we summarized the important pathogenesis of HS-induced liver injury that has been confirmed so far. In addition to the comprehensive effect of systemic factors such as heat cytotoxicity, coagulopathy, and systemic inflammatory response syndrome, excessive hepatocyte cell pyroptosis, dysfunction of Kupffer cells, abnormal expression of heat shock protein expression, and other factors are also involved in the pathogenesis of HS-induced liver injury. Furthermore, we have also established the current therapeutic strategies for HS-induced liver injury. Our study is of great significance in promoting the understanding of the pathogenesis and treatment of HS-induced liver injury.

Background: Acute respiratory distress syndrome (ARDS) remains a challenge because of its high morbidity and mortality. Circulation histones levels in ARDS patients were correlated to disease severity and mortality. This study examined the impact of histone neutralization in a rat model of acute lung injury (ALI) induced by a lipopolysaccharide (LPS) double-hit.Methods: Sixty-eight male Sprague-Dawley rats were randomized to sham (N = 8, received saline only) or LPS (N = 60). The LPS double-hit consisted of a 0.8 mg/kg intraperitoneal injection followed after 16 h by 5 mg/kg intra-tracheal nebulized LPS. The LPS group was then randomized into five groups: LPS only; LPS +5, 25, or 100 mg/kg intravenous STC3141 every 8 h (LPS + L, LPS + M, LPS + H, respectively); or LPS + intraperitoneal dexamethasone 2.5 mg/kg every 24 h for 56 h (LPS + D). The animals were observed for 72 h.Results: LPS animals developed ALI as suggested by lower oxygenation, lung edema formation, and histological changes compared to the sham animals. Compared to the LPS group, LPS + H and +D groups had significantly lower circulating histone levels and lung wet-to-dry ratio, and the LPS + D group also had lower BALF histone concentrations; the blood neutrophils and platelets counts in LPS + D group did not change, meanwhile, the LPS + L, +M and +H groups had significantly lower neutrophil counts and higher platelet counts in the blood; the total number of BALF WBC, platelet counts, MPO and H3 were significantly lower in the LPS + L, +M, +H and +D groups than in the LPS only group; and the degree of inflammation was significantly less in the LPS + L, +M, +H and +D groups, moreover, inflammation in the LPS + L, +M and +H animals showed a dose-dependent response; finally, the LPS + L, +M, +H and +D groups had improved oxygenation compared to the LPS group, and there were no statistical differences in PCO2 or pH among groups. All animals survived.Conclusion: Neutralization of histone using STC3141, especially at high dose, had similar therapeutic effects to dexamethasone in this LPS double-hit rat ALI model, with significantly decreased circulating histone concentration, improved acute lung injury and oxygenation.

Abstract Background Arterial enhancement fraction (AEF), derived from triphasic CT scans, is considered to indirectly reflect the ratio of hepatic arterial perfusion to total perfusion. The purpose of this study was to retrospectively investigate the relationship between AEF and treatment response and survival in hepatocellular carcinoma (HCC) patients treated with drug-eluting bead (DEB) TACE. Methods AEF of primary lesion (AEFpre) and residual tumor (AEFpost) in 158 HCC patients were obtained from triphasic liver CT examinations pre- and post-treatment. Wilcoxon-signed rank test was used to compare the AEFpre and AEFpost for different response groups. Survival curves for overall survival (OS) in patients with different AEF were created by using Kaplan-Meier method. Cox regression analyses were used to determine the association between AEF and OS. Results There was no correlation between AEFpre and treatment response. After DEB-TACE, AEFpost was significantly lower than AEFpre either in the partial response group (38.9% vs. 52.7%, p 57.95% (HR = 1.66, p = 0.019) or AEFpost > 54.85% (HR = 2.47, p

The dysfunctional immune response and multiple organ injury in sepsis is a recurrent theme impacting prognosis and mortality, while the lung is the first organ invaded by sepsis. To systematically elucidate the transcriptomic changes in the main constituent cells of sepsis-injured lung tissue, we applied single-cell RNA sequencing to the lung tissue samples from septic and control mice and created a comprehensive cellular landscape with 25044 cells, including 11317 immune and 13727 non-immune cells. Sepsis alters the composition of all cellular compartments, particularly neutrophils, monocytes, T cells, endothelial, and fibroblasts populations. Our study firstly provides a single-cell view of cellular changes in septic lung injury. Furthermore, by integrating bulk sequencing data and single-cell data with the Scissors-method, we identified the cell subpopulations that are most associated with septic lung injury phenotype. The phenotypic-related cell subpopulations identified by Scissors-method were consistent with the cell subpopulations with significant composition changes. The function analysis of the differentially expressed genes (DEGs) and the cell-cell interaction analysis further reveal the important role of these phenotype-related subpopulations in septic lung injury. Our research provides a rich resource for understanding cellular changes and provides insights into the contributions of specific cell types to the biological processes that take place during sepsis-induced lung injury.

Hepatocellular carcinoma (HCC) is a common malignant tumor with a poor prognosis. Epigenetic dysregulation is now considered to be related to hepatocarcinogenesis. However, it is unclear how epigenetic-related genes (ERGs) contribute to the prognosis of HCC. In this study, we used the TCGA database to identify prognostic ERGs that were differentially expressed in HCC patients. Then, using least absolute shrinkage and selection operator (LASSO) regression analysis, a six-gene signature was constructed, and patients were divided into high- and low-risk groups. Validation was performed on HCC patients from the ICGC database. Patients in the high-risk group had a significantly lower chance of survival than those in the low-risk group (p < 0.001 in both databases). The predictive ability of the signature was determined by the receiver operating characteristic (ROC) curve. The risk score was then shown to be an independent prognostic factor for the overall survival (OS) of HCC patients based on the results of univariate and multivariate analyses. We also created a practical nomogram combining the prognostic model with other clinical features. Moreover, functional enrichment analysis revealed that these genes are linked to tumor immunity. In conclusion, our findings showed that a novel six-gene signature related to epigenetics can accurately predict the occurrence and prognosis of HCC.

Our study is the first to illustrate the age and geographic distribution differences in the epidemiology of prostate cancer from 1990 to 2019 in China. Prostate cancer (PC) is a malignant tumor derived from prostate epithelial cells and is one of the most commonly diagnosed cancers in men. In recent years, the global incidence and the annual deaths number of PC showed a continuous increase, which has caused a huge disease burden on human health. In terms of the global average, the incidence and mortality of PC in China are relatively low. However, the age-standardized incidence rate of PC was 17.3/100,000 in 2019 in China, with a 95.2% rise compared to 1990, while the global growth rate of incidence rate over the same period is 13.2%. This showed that the development trend of PC in China is not optimistic. There are few precise studies on the epidemiology of PC in China. After the general analysis strategy used in the Global Burden of Diseases, Injuries and Risk Factors Study (GBD) 2019, we elaborated on the incidence, mortality, and disability-adjusted life-years (DALYs) and the corresponding age-standardized rate of the Chinese PC population from 1990 to 2019 according to different ages and provinces. We used joinpoint regression analysis to estimate the incidence and mortality trends. Our analysis shows that elderly people over 80 are still the main focus of incidence and death. The epidemiology and disease burden of PC of different provinces in China show obvious regional differences, and some certain provinces such as HongKong, Macao, and Zhejiang should be paid more attention. More targeted and effective strategies should be developed to reduce the burden of PC in China.

Aims To retrospectively compare the efficacy of transcatheter chemoembolization (TACE) plus percutaneous radiofrequency ablation (PRFA) (hereafter, TACE + PRFA) and laparoscopic radiofrequency ablation (LRFA) in the treatment of inoperable hepatocellular carcinoma (HCC). Methods From July 2014 to December 2017, 132 consecutive patients with inoperable HCC were treated with TACE + PRFA (n = 86) or LRFA (n = 46). Overall survival (OS) and recurrence-free survival (RFS) were analyzed using log-rank test and Cox regression analysis. Propensity score matched (PSM) analyses based on patient and tumor characteristics were also conducted. Additionally, we performed exploratory analyses to determine the effectiveness of TACE + PRFA and LRFA in clinically relevant subsets. Results The baseline characteristics of TACE + PRFA patients displayed relatively inferior liver status and a higher rate of BCLC-B disease. For unmatched patients, median OS (55.0 vs. 42.0 months; p = .019) and RFS (20.0 vs. 11.0 months; p

Gamma-delta (γδ) T cells are a small subset of T cells that are reported to have a proinflammatory role in the pathophysiology of cerebral ischemia stroke (CIS). Upon activation by interleukin-1 beta (IL-1β), IL-23 and IL-18, γδ T cells are stimulated to secrete various cytokines, such as IL-17a, IL-21, IL-22, and interferon-gamma (IFN-γ). In addition, they all play a pivotal role in the inflammatory and immune responses in ischemia. Nevertheless, the exact mechanisms responsible for γδ T cell proinflammatory functions remain poorly understood, and more effective therapies targeting at γδ T cells and cytokines they release remain to be explored, particularly in the context of CIS. CIS is the second most common cause of death and the major cause of permanent disability in adults worldwide. In this review, we focus on the neuroinflammatory and immune functions of γδ T cells and related cytokines, intending to understand their roles in CIS, which may be crucial for the development of novel effective clinical applications.

Acute lung injury (ALI) is the most common type of organ injury in sepsis, with high morbidity and mortality. Sepsis is characterized by an inappropriate inflammatory response while neutrophils exert an important role in the excessive inflammatory response. The discovery of specialized pro-resolving mediators (SPMs) provides a new direction for the treatment of a series of inflammatory-related diseases including sepsis. Among them, the regulation of Maresin1 on immune cells was widely demonstrated. However, current research on the regulatory effects of Maresin1 on immune cells has remained at the level of certain cell types. Under inflammatory conditions, the immune environment is complex and immune cells exhibit obvious heterogeneity. Neutrophils play a key role in the occurrence and development of septic lung injury. Whether there is a subpopulation bias in the regulation of neutrophils by Maresin1 has not been elucidated. Therefore, with the well-established cecal ligation and puncture (CLP) model and single-cell sequencing technology, our study reveals for the first time the regulatory mechanism of Maresin1 on neutrophils at the single-cell level. Our study suggested that Maresin1 can significantly reduce neutrophil infiltration in septic lung injury and that this regulatory effect is more concentrated in the Neutrophil-Cxcl3 subpopulation. Maresin1 can significantly reduce the infiltration of the Neutrophil-Cxcl3 subpopulation and inhibit the expression of related inflammatory genes and key transcription factors in the Neutrophil-Cxcl3 subpopulation. Our study provided new possibilities for specific modulation of neutrophil function in septic lung injury.

Abstract Background The comparative efficacy of ancillary drugs on sevoflurane related emergence agitation (EA) in children undergoing ophthalmic surgery remains controversial. Methods The databases were retrieved in an orderly manner from the dates of their establishment to October, 2018, including PubMed, The Cochrane Library and Web of Science, to collect randomized controlled trials (RCT) of different anesthetic drugs combined with sevoflurane for ophthalmic surgery. Then a network meta-analysis was conducted using R and Stata 12.0 softwares. Results The meta-analysis showed that, in reducing sevoflurane related EA, dexmedetomidine, ketamine, propofol, fentanyl, midazolam, sufentanil, remifentanil and clonidine were superior to placebo (P

This paper presents a concept and an implementation of a linearized analog photonic link for wideband wireless communication that yields improved adjacent channel leakage ratio (ACLR). The link consists of two parallel Mach-Zehnder modulators (MZMs) driven by two lasers, and a modified uni-traveling-carrier photodetector capable of outputting high RF power when assisted by an erbium-doped fiber amplifier. The third-order intermodulation (IMD3) attributed to the MZM transfer function is suppressed by asymmetric RF and optical feeding that impose a π-phase difference between the signals in the two MZM channels. Long-Term Evolution (LTE) signals of various bandwidths are used to validate this broadband linearization approach experimentally. It is demonstrated that with this approach the first ACLR (ACLR1) can be improved by 19.2 dB for a 10-MHz LTE signal and 18.1 dB for a 20-MHz LTE signal at the cost of approximately 2-dB link gain penalty.

MicroRNAs are small noncoding RNAs which regulate gene expression at the posttranscriptional level. miR-155 is encoded by the miR-155 host gene (miR155HG), also known as the noncoding B cell integration cluster (BIC). MicroRNAs are widely expressed in various hematopoietic cells and are involved in regulating the immune system. In this review, we summarized how miR-155 modulates specific immune cells and the regulatory role of miR-155 in sepsis. miR-155 is expressed by different populations of innate and adaptive immune cells and is involved in the regulation of development, proliferation, and function in these cells. Sepsis is associated with uncontrollable inflammatory responses, accompanied by unacceptably high mortality. Due to the inadequacy of diagnostic markers as well as treatment strategies, treating sepsis can be a huge challenge. So far, a large number of experiments have shown that the expression of miR-155 is increased at an early stage of sepsis and that this increase is positively correlated with disease progression and severity. In addition, by blocking the proinflammatory effects of miR-155, it can effectively improve sepsis-related organ injury, providing novel insights to identify potential biomarkers and therapeutic targets for sepsis. However, since most of the current research is limited to animal experiments, further clinical research is required to determine the function of miR-155 and its mechanism related to sepsis.

Endoplasmic reticulum (ER) stress is an evolutionarily conserved adaptive response that contributes to deal with the misfolded or unfolded protein in the lumen of the ER and restore the ER homeostasis. However, excessive and prolonged ER stress can trigger the cell-death signaling pathway which causes cell death, usually in the form of apoptosis. It is generally accepted that inappropriate cellular apoptosis and a series of the subsequent inflammatory response and oxidative stress can cause disturbance of normal physiological functions and organ damage. A lot of evidence shows that the excessive activation of the ER stress contributes to the pathogenesis of many kinds of diseases and inhibiting the inappropriate stress is of great significance for maintaining the normal physiological function. In recent years, Sirtuin1 (SIRT1) has become a research hotspot on ER stress. As a master regulator of ER stress, increasing evidence suggests that SIRT1 plays a positive role in a variety of ER stress-induced organ damage via multiple mechanisms, including inhibiting cellular apoptosis and promoting autophagy. Furthermore, a lot of factors have shown effective regulation of SIRT1, which indicates the feasibility of treating SIRT1 as a target for the treatment of ER stress-related diseases. We summarize and reveal the molecular mechanisms underlying the protective effect of SIRT1 in multiple ER stress-mediated organ damage in this review. We also summed up the possible adjustment mechanism of SIRT1, which provides a theoretical basis for the treatment of ER stress-related diseases.

Acute kidney injury (AKI) is one of the most common and serious complications of sepsis in which the inflammatory cascade plays a crucial role. There is now increasing evidence that lipid mediators derived from the omega-3 fatty acid docosahexaenoic acid (DHA) have potent anti-inflammatory effects that promote the timely regression of acute inflammation. In this study, we investigated the protective effects and molecular mechanism of a novel DHA-derived lipid mediator Maresin 1 (MaR1) on AKI in septic mice. The cecal ligation and puncture (CLP) was used to establish a sepsis mice model. As a result, we found that MaR1 significantly increased the 7-day survival rate of septic mice and the anti-inflammatory factor IL-10 while reducing bacterial load and pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β). In addition, MaR1 dose dependently reduced renal injury scores and serum creatinine and urea nitrogen levels in septic mice while inhibiting renal neutrophil infiltration and myeloperoxidase (MPO) activity. In terms of signaling pathway, we found that MaR1 inhibits the expression of phosphorylated p65, Stat3, JNK, ERK, and p38 and significantly reduces nuclear translocation of p65. In conclusion, our results indicate that MaR1 is able to reduce neutrophil infiltration and inhibit nuclear factor-kappa B/signal transducer and activator of transcriptor 3/mitogen-activated protein kinase (NF-κB/STAT3/MAPK) activity and regulate inflammatory cytokine level to inhibit inflammatory response and thereby weaken sepsis-associated AKI in mice.

Background: Early recognition of the risk of acute respiratory distress syndrome (ARDS) after cardiopulmonary bypass (CPB) may improve clinical outcomes. The main objective of this study was to identify proteomic biomarkers and develop an early prediction model for CPB-ARDS. Methods: The authors conducted three prospective nested cohort studies of all consecutive patients undergoing cardiac surgery with CPB at Union Hospital of Tongji Medical College Hospital. Plasma proteomic profiling was performed in ARDS patients and matched controls (Cohort 1, April 2021-July 2021) at multiple timepoints: before CPB (T1), at the end of CPB (T2), and 24 h after CPB (T3). Then, for Cohort 2 (August 2021-July 2022), biomarker expression was measured and verified in the plasma. Furthermore, lung ischemia/reperfusion injury (LIRI) models and sham-operation were established in 50 rats to explore the tissue-level expression of biomarkers identified in the aforementioned clinical cohort. Subsequently, a machine learning-based prediction model incorporating protein and clinical predictors from Cohort 2 for CPB-ARDS was developed and internally validated. Model performance was externally validated on Cohort 3 (January 2023-March 2023). Results: A total of 709 proteins were identified, with 9, 29, and 35 altered proteins between ARDS cases and controls at T1, T2, and T3, respectively, in Cohort 1. Following quantitative verification of several predictive proteins in Cohort 2, higher levels of thioredoxin domain containing 5 (TXNDC5), cathepsin L (CTSL), and NPC intracellular cholesterol transporter 2 (NPC2) at T2 were observed in CPB-ARDS patients. A dynamic online predictive nomogram was developed based on three proteins (TXNDC5, CTSL, and NPC2) and two clinical risk factors (CPB time and massive blood transfusion), with excellent performance (precision: 83.33%, sensitivity: 93.33%, specificity: 61.16%, and F1 score: 85.05%). The mean area under the receiver operating characteristics curve (AUC) of the model after 10-fold cross-validation was 0.839 (95% CI: 0.824-0.855). Model discrimination and calibration were maintained during external validation dataset testing, with an AUC of 0.820 (95% CI: 0.685-0.955) and a Brier Score of 0.177 (95% CI: 0.147-0.206). Moreover, the considerably overexpressed TXNDC5 and CTSL proteins identified in the plasma of patients with CPB-ARDS, exhibited a significant upregulation in the lung tissue of LIRI rats. Conclusions: This study identified several novel predictive biomarkers, developed and validated a practical prediction tool using biomarker and clinical factor combinations for individual prediction of CPB-ARDS risk. Assessing the plasma TXNDC5, CTSL, and NPC2 levels might identify patients who warrant closer follow-up and intensified therapy for ARDS prevention following major surgery. [ABSTRACT FROM AUTHOR]