Kai Hou

Background: Lung cancer remains a leading cause of cancer-related death globally, highlighting the need for improved prognostic tools and personalized treatment strategies. This study aims to identify proteomic biomarkers and develop an AI-driven machine learning model for lung cancer prognosis, patient stratification, and immunotherapy response prediction. Methods: We analysed TCGA LUAD proteomic/clinical data using LASSO and multivariable Cox to derive an eight‑protein risk score; immune infiltration (CIBERSORT), PCA, TIDE/TCIA, and external validation (K21-12) were performed. Findings: Key proteins—XBP1, ETS1, YB1_pS102, ERALPHA_pS118, LCK, PGM1, TIGAR, and Patched—were identified as significant predictors of overall survival. The resulting prognostic model stratified patients into high- and low-risk groups with significant survival differences (p < 0.001), yielding 1-, 2-, and 3-year survival AUCs of 0.738, 0.755, and 0.661. High-risk patients exhibited increased immunosuppressive cells (e.g., activated NK cells, resting mast cells). Validation via an independent cohort (K21-12) confirmed robustness, while Tumor Immune Dysfunction and Exclusion (TIDE) analysis assessed immunotherapy response. Interpretation: This integrated approach demonstrates strong clinical potential for risk stratification and personalized therapy in lung cancer.

Myocarditis is a potentially fatal disease that can progress to inflammatory dilated cardiomyopathy (DCMi), a condition that is a leading cause of noncongenital heart failure in young adults. However, the mechanisms driving the transition from acute myocarditis to DCMi remain poorly understood. Although IL-17A-mediated inflammation is a well-known driver of this progression, the intracellular regulators that sustain and amplify this response remain unclear. Here, we identify the E3 ubiquitin ligase TRIM21, which is upregulated in the hearts of DCMi patients and experimental autoimmune myocarditis (EAM) mice, as a key amplifier of IL-17A-driven inflammation in cardiac fibroblasts (CFs), promoting disease progression and fibrosis. TRIM21 deficiency significantly attenuates EAM progression, reducing inflammatory cell infiltration and fibrotic remodeling. Mechanistically, TRIM21 is induced by IL-17A in CFs and promotes K27-linked polyubiquitination and lysosomal degradation of TRAF3, a negative regulator of IL-17A signaling, thereby establishing a self-reinforcing IL-17A-TRIM21–TRAF3 positive feedback loop. Finally, specific knockdown of TRIM21 in CFs via the AAV9-Postn strategy effectively alleviates EAM severity. These findings identify TRIM21 as an intracellular mediator of sustained IL-17A signaling in myocarditis and highlight its potential as a therapeutic target for preventing progression to DCMi.

With the rapid development of new generations of antitumor therapies, the average survival time of cancer patients is expected to be continuously prolonged. However, these therapies often lead to cardiotoxicity, resulting in a growing number of tumor survivors with cardiovascular disease. Therefore, a new interdisciplinary subspecialty called “cardio-oncology” has emerged, aiming to detect and treat cardiovascular diseases associated with tumors and antitumor therapies. Recent studies have highlighted the role of ferroptosis in both cardiovascular and neoplastic diseases. The balance between intracellular oxidative stress and antioxidant defense is crucial in regulating ferroptosis. Tumor cells can evade ferroptosis by upregulating multiple antioxidant defense pathways, while many antitumor therapies rely on downregulating antioxidant defense and promoting ferroptosis in cancer cells. Unfortunately, these ferroptosis-inducing antitumor therapies often lack tissue specificity and can also cause injury to the heart, resulting in ferroptosis-induced cardiotoxicity. A range of cardioprotective agents exert cardioprotective effects by inhibiting ferroptosis. However, these cardioprotective agents might diminish the efficacy of antitumor treatment due to their antiferroptotic effects. Most current research on ferroptosis only focuses on either tumor treatment or heart protection but rarely considers both in concert. Therefore, further research is needed to study how to protect the heart during antitumor therapies by regulating ferroptosis. In this review, we summarized the role of ferroptosis in the treatment of neoplastic diseases and cardiovascular diseases and also attempted to propose further research directions for ferroptosis in the field of cardio-oncology.

Introduction: Lung cancer is the most prevalent cancer with high mortality in China, and it is associated with the dysbiosis of the lung microbiome. This study attempted to screen for specific microorganisms as potential biomarkers for distinguishing benign lung disease from lung cancer.Methods: Bronchoalveolar lavage fluid (BALF) sample was selected in the study instead of saliva to avoid contamination with oral microorganisms, and microbial taxonomic and functional differences in BALF samples from patients with lung cancer and those with those from patients with benign lung diseases were performed based on metagenomic next‐generation sequencing, for the first time, so that microorganisms other than bacteria could be included.Results: The results showed that the intrasample diversity of malignant samples was different from benign samples, and the microbial differences among malignant samples were smaller, with lower microbial diversity, significantly changed microbial abundance and metabolic functions. Metabolic function analysis revealed amino acid‐related metabolism was more prevalent in benign samples, whereas carbohydrate‐related metabolism was more prevalent in malignant samples. By LEfSe, Metastat and Random Forest analysis, we identified a series of important differential microorganisms. Importantly, the model combining five key genera plus one tumor marker (neuron‐specific enolase) as indicators presented the optimal disease typing performance.Conclusion: Thus results suggest the value of these differential microorganisms enriched in tumors in mechanism research and may be potential new targets for lung cancer therapy. More importantly, the biomarkers identified in this study can be conducive to improve the clinical diagnosis of lung cancer and have good application prospects.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been shown to inhibit pyroptosis and apoptosis, which play important roles in the development and progression of contrast-induced acute kidney injury (CI-AKI). However, to the best of our knowledge, no studies have investigated the potential effect of PCSK9 inhibitors on the prevalence of CI-AKI after percutaneous coronary intervention (PCI). This study aimed to determine whether PCSK9 inhibitors are associated with the prevalence of CI-AKI. The medical records of 309 (mean age, 63.35 years; 71.84% male) patients with acute myocardial infarction who underwent PCI at our institution were retrospectively analyzed. Overall, 149 and 160 patients were assigned to the evolocumab and control groups, respectively. Serum creatinine levels were examined preoperatively and 24–72 h postoperatively and compared between groups. Data were grouped according to the occurrence of CI-AKI, and a univariate analysis was conducted to exclude suspected influencing factors that led to CI-AKI occurrence. After adjusting for confounding factors, a logistic regression analysis was performed to assess the association between evolocumab administration (independent variable) and CI-AKI occurrence (dependent variable). The prevalence of CI-AKI was significantly lower in the evolocumab group (6.7%) than in the control group (20.0%; ). We further evaluated the correlation between exposure factor and outcome. The relative risk(RR) between the use of evolocumab and the occurrence of CI-AKI was 0.34(95% CI 0.17-0.66,p<0.01).This result indicate a significant association between the use of evolocumab and a reduction in the incidence of CI-AKI.The logistic regression analysis results revealed that evolocumab was significantly associated with CI-AKI. The use of PCSK9 inhibitors, hydration therapy, and statin administration appears promising for preventing CI-AKI in patients with acute myocardial infarction undergoing PCI.

The clinical application of orbital magnetic resonance (MR) T2-mapping imaging in detecting the disease activity of Graves’ ophthalmopathy (GO), and the predictive values of therapy response to intravenous glucocorticoid (ivGC) were investigated. Approved by the local institutional review board (IRB), 106 consecutive patients with GO were included in this prospective study. All subjects were divided into two groups according to the patients’ clinical activity score (CAS): the CAS positive group (CAS ≥3) or the CAS negative group (CAS 2) were measured by 3D T2-mapping MR sequence before and after methylprednisolone treatment, so as the CAS and some ophthalmic examinations including visual acuity, intra-ocular pressure, eyeball movement, diplopia and proptosis. In addition, 24 healthy volunteers were recruited as the control group. The mean T2RT and AEOMs in CAS positive group were higher than those in CAS negative group. Both CAS positive and negative groups had significantly higher mean T2RT and AEOMs than the control group (P<0.01). There was a positive correlation between T2RT and AEOMs values in GO patients, both of them had a positive correlation with CAS and the ophthalmic examinations. It was concluded that to evaluate the activity of GO, CAS was mostly related to inflammation symptoms of ocular surface, more than that, T2RT and AEOMs were also related to abnormal findings of the ophthalmic examinations including high ocular pressure, impaired eyeball movement, diplopia and proptosis. T2RT and AEOMs can reflex the inflammation state of ocular muscles better. CAS combined with 3D T2-mapping MR imaging could improve the sensitivity of detection of active GO so as the prediction and evaluation of the response to methylprednisolone treatment.