ShenJing Hospital of China Medical University

Cysteinyl leukotrienes (CysLTs), as potent lipid inflammatory mediators, play a pivotal role in systemic multi-organ inflammation and inter-organ communication through interactions with their receptors (CysLTRs). However, However, the function of CysLT3R is unclear and lacks a network of cross-organ metabolite interactions, and the clinical use of leukotriene receptor antagonists (LTRAs) has certain limitations. This review systematically synthesizes existing evidence and proposes future directions by clarifying receptor subtype specificity, optimizing targeted therapies, exploring CysLTs’ applications in neuroimmunology, and elucidating the dual roles of CysLTs in chronic inflammation. It is indicated that CysLTs activate eosinophils, mast cells, and airway tuft cells, driving type 2 immune responses and mucus secretion in the lungs, thereby exacerbating respiratory diseases such as asthma. In the nervous system, CysLTs aggravate neurodegenerative disorders like cerebral ischemia and Alzheimer’s disease by disrupting the blood-brain barrier, promoting glial activation, and inducing neuronal damage. In the gut, CysLTs regulate anti-helminth immunity via the tuft cell-ILC2 pathway and collaborate with prostaglandin D2 (PGD2) to modulate bile excretion and mucosal protection. Furthermore, CysLTs mediate communication through the gut-lung and gut-brain axes via metabolites such as succinate, contributing to cross-organ inflammatory regulation. In conclusion, this review highlights the complex roles of CysLTs in chronic inflammation, providing a theoretical foundation for precise intervention in multi-organ inflammatory diseases, which provides a theoretical framework for precision interventions in multi-organ inflammatory diseases and inspires interdisciplinary breakthroughs.

Purpose This study aims to develop an effective machine learning (ML)-based predictive model for the recurrence of borderline ovarian tumor (BOT), and provide the guidelines of accurate clinical diagnosis and precise treatment for patients. Method A total of 660 patients diagnosed with BOT were included in this study. Statistical testing methods were employed to identify the most influential factors. At the same time, five machine learning-based models—random forest (RF), logistic regression (LR), gradient boosting (GB), multilayer perceptron (MLP), and support vector machine (SVM)—were utilized to construct recurrence prediction models. Model validity was assessed using five metrics: area under the curve (AUC), positive predictive value (PPV), accuracy (ACC), recall (REC), specificity (SPE), and the optimal model was selected based on these performance metrics. The calibration curve further illustrates the reliability of the model. Then, the optimal ML-based model determined the importance of features using SHAP values. Additionally, CIC and DCA, along with recurrence-free survival analysis, were employed to further assess the clinical value of the optimal model. Results The RF model demonstrated superior predictive performance. Additionally, the SHAP analysis of the RF-based model provides the key clinical factors associated with the recurrence of BOT. Furthermore, the DCA and CIC shows the clinical application value of the RF-based model. Moreover, random forest-recurrence free survival (rf-RFS) model validate the effectiveness of the proposed method personalized treatment strategies and informed clinical decision-making of the recurrence of BOT. Conclusion The RF-based model offers an effective tool for predicting BOT recurrence, with a user-friendly web-based calculator developed to aid clinical decision-making.

Background Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) is a type of necrotizing vasculitis with poor prognosis, which is more severe in children. Classifying AAV patients may be helpful for diagnosis and management. However, present classification criteria for pediatric AAV are developed mainly based on adults, which have limitations in clinical practice. In this study, we introduced an updated algorithm based on the European Medicines Agency (EMA) algorithm in conjunction with the American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) criteria. This new approach aims to resolve the issue of duplicate classification present in the 2022 ACR/EULAR criteria and to refine the existing EMA algorithm. Methods This study included 179 pediatric patients diagnosed with AAV across 17 centers in China. Patients were classified using the EMA algorithm, the ACR/EULAR criteria, and the EMA-ACR/EULAR algorithm. The Kappa value and Net Reclassification Index (NRI) were used to evaluate the classification performance of these criteria. Results According to the EMA algorithm, 136 (76.0%) patients were classified with microscopic polyangiitis (MPA) and 14 (7.8%) with granulomatosis with polyangiitis (GPA), while 29 (16.2%) remained unclassifiable. According to the ACR/EULAR criteria, 145 (81.0%) patients were classified with MPA, 14 (7.8%) with GPA, 2 (1.1%) with eosinophilic granulomatosis with polyangiitis (EGPA), and 4 (2.2%) with both MPA and GPA, while 14 (7.8%) remained unclassifiable. The EMA-ACR/EULAR algorithm classified 124 patients (69.3%) as MPA, 26 (14.5%) as GPA, and 2 (1.1%) as EGPA, while 27 (15.1%) were unclassified. The Kappa values between the EMA algorithm and ACR/EULAR criteria for GPA and MPA were 0.225 [95% confidence interval (CI) 0.000–0.456, P = 0.003] and 0.357 (95% CI 0.196–0.518, P < 0.001). Compared to these two criteria, the EMA-ACR/EULAR algorithm demonstrated positive NRIs in the classification of both GPA (0.702, 95% CI 0.258–1.146, P = 0.002; 0.547 95% CI 0.150–0.944, P = 0.007) and MPA (0.425, 95% CI 0.209–0.642, P < 0.001; 0.519, 95% CI 0.305–0.733, P < 0.001). Conclusions The EMA-ACR/EULAR algorithm addresses the limitations of the 1990 ACR criteria within the EMA framework and resolves the issue of duplicate classification in the 2022 ACR/EULAR criteria. However, further research is necessary to validate the superiority of the EMA-ACR/EULAR algorithm in the clinical classification of pediatric AAV patients. Graphic abstract

Microwave thermotherapy is favored in clinical practice for breast cancer conservation strategies due to its minimally invasive characteristic. Nevertheless, the immunosuppressive tumor microenvironment (TME) significantly attenuates the therapeutic efficacy of anti‐tumor immune response, posing challenges in effectively preventing tumor recurrence and metastasis. Pyroptosis, a recently identified form of programmed cell death triggered by inflammasomes, presents unique inflammatory and immunogenic properties that hold promise for cancer immunotherapy. Herein, microwave‐responsive AlEu‐MOFs are designed and synthesized to boost NLRP3‐mediated pyroptosis via a “Triple Initiating” tactic for breast cancer microwave‐immunotherapy. The potent microwave thermal effect of AEM facilitates the up‐regulation of HSP90, thereby initiating NLRP3 expression. Concurrently, it induces mitochondrial dysfunction to generate substantial quantities of ROS, further enhancing NLRP3 expression to achieve a targeted amplification of microwave thermotherapy‐induced pyroptosis. Simultaneously, the microwave‐responsive directed anchoring release of highly active metal ions promotes the activation of the NLRP3 inflammasome jointly, ultimately inducing high‐efficiency pyroptosis. This innovative “2M” (materials and methods) dual‐pronged strategy not only significantly inhibits primary tumor proliferation, but also further impedes distant tumor progression and lung metastasis. This work provides a novel strategy to accurately and effectively achieve pyroptosis and offers a new approach to overcome the obstacles of clinical microwave thermotherapy.

Background Abiraterone is a 17α-hydroxylase/C17-20 lyase inhibitor used for the treatment of metastatic castration-resistant prostate cancer (CRPC). This multi-center, randomized, open-label, active-controlled phase II study compared the pharmacodynamics (PD), pharmacokinetics (PK), and safety of abiraterone acetate tablets (II) (AAT[II]), a new formulation of abiraterone acetate, and ZYTIGA®, the originator abiraterone acetate (OAA), in patients with metastatic CRPC. Methods Patients were randomized 1:1 to receive 300 mg AAT(II) daily plus 5 mg prednisone twice daily or 1000 mg OAA daily plus 5 mg prednisone twice daily for 84 days. The primary endpoint was the serum testosterone level (rounded-up) on Day 9 and/or Day 10. Absolute testosterone concentration, prostate-specific antigen (PSA) concentration, steady-state PK of abiraterone, and safety were also evaluated. Results Sixty-nine patients were enrolled in the study, with 35 assigned to AAT(II) and 34 to OAA. The least squares (LS) mean (standard error) of serum testosterone concentration (rounded-up) on Day 9 and/or Day 10 were 1.075 (0.034) and 1.000 (0.034) in the AAT(II) and OAA groups, respectively. The geometric mean ratio (AAT[II] vs. OAA) was 1.053 (90% confidence interval [CI], 0.998 to 1.110) and the LS mean difference was 0.075 (95% CI, -0.021 to 0.171). The 90% CI fell within the 80.0% to 125.0% equivalence limits, suggesting equivalent PD effect of the two formulations. AAT(II) also exhibited high testosterone inhibition rate (> 90% at all visits) and PSA-50 rate (> 65% on Days 56 and 84), which were comparable to that of OAA. AAT(II) also demonstrated an improved safety profile with lower incidence of adverse events compared to OAA. Conclusions AAT(II) at 300 mg plus prednisone demonstrated equivalent PD as OAA at 1000 mg plus prednisone in reducing serum testosterone on Day 9 and/or Day 10, and the effect was maintained up to the end of the study. Compared to OAA, AAT(II) was given at a much lower dosage and was not affected by food consumption. AAT(II) was well tolerated, and no new safety issues were found. Trial registration ClinicalTrials.gov, NCT04862091.

Opinion Statement The combination of stereotactic ablative radiotherapy (SABR) with immune checkpoint inhibitors, known as iSABR, marks a significant evolution in treating early-stage, inoperable non-small cell lung cancer (NSCLC). Managing these cases requires a multidisciplinary approach involving radiation and medical oncologists. Clinical evidence from a meta-analysis of seven studies, including 462 patients, indicates that iSABR may offer better outcomes than SABR alone. The analysis showed significantly improved progression-free survival (PFS) rates at 1-, 2-, and 3-year follow-ups for iSABR compared to SABR. There was also a trend toward better overall survival (OS) with iSABR. Subgroup analyses highlighted enhanced 3-year PFS with programmed death-1 (PD-1) inhibitors and doses per fraction ≥ 12.5 Gy. While iSABR slightly increased the risk of grade ≥ 3 adverse events like pneumonitis, fatigue, and skin reactions, these risks are generally manageable within a multidisciplinary treatment framework. In conclusion, iSABR demonstrates potential benefits and manageable risks in phase I/II trials for early-stage, inoperable NSCLC, with improved PFS and acceptable toxicity. These findings warrant further investigation in a larger phase III prospective randomized controlled trial to validate efficacy, optimize protocols, and establish long-term safety.

Acute lung injury (ALI) is a life-threatening condition characterized by severe pulmonary dysfunction, with alveolar type II epithelial cell (ACE-II) senescence playing a pivotal role in its progression. In this study, we developed pH/reactive oxygen species (ROS) dual-responsive nanoparticles (GNPsanti-SP-C) for the targeted delivery of Growth Differentiation Factor 15 (GDF15) to counteract ACE-II senescence. These nanoparticles (NPs) effectively activate the AMP-activated protein kinase (AMPK)/Sirtuin 1 (SIRT1) signaling pathway, inducing the mitochondrial unfolded protein response (UPRmt) and reversing senescence-associated cellular dysfunction. GNPsanti-SP-C were systematically engineered and demonstrated robust pH/ROS sensitivity, efficient GDF15 release, and precise ACE-II targeting. In lipopolysaccharide (LPS)-induced ALI mouse model, GNPsanti-SP-C treatment significantly mitigated lung injury, reduced inflammatory responses, and enhanced pulmonary function, as evidenced by decreased inflammatory markers, lung edema, and improved histopathology. Single-cell transcriptomic and proteomic analyses revealed increased ACE-II cell populations, reduced expression of senescence markers, and upregulation of AMPK/SIRT1 signaling. In vitro studies further demonstrated that UPRmt activation is associated with the NPs’ therapeutic effects, suggesting a potential role in their mechanism of action. These findings demonstrate the potential of GDF15-loaded dual-responsive NPs as an innovative strategy to address cellular senescence and alleviate ALI-associated pulmonary damage. Graphical abstract

Exosomes participate in the formation of the tumor metastatic microenvironment (TME) by delivering tumor‐specific substances. However, current studies mostly focus on exosomal RNA and proteins and lack an in‐depth exploration of exosomal DNA. It is discovered that PIK3CAH1047R mutant DNA in colorectal cancer (CRC) cell‐derived exosomes can be delivered into recipient fibroblasts, where they are transcribed and translated, ultimately leading to the activation of fibroblasts into cancer‐associated fibroblasts (CAFs) through interaction with the endogenous P85 regulatory subunit of the phosphatidylinositol 3‐kinase (PI3K) pathway. CAFs have facilitated tumor cell migration in vitro and promote lung metastasis in vivo by secreting elevated levels of IL6. Additionally, the PIK3CAH1047R mutation is detected in CAFs at both the primary and metastatic sites, suggesting that it may play a role in promoting metastasis by influencing the TME. Moreover, patients with CRC harboring the PIK3CAH1047R mutation and exhibiting elevated levels of IL6 are significantly more likely to metastasize. These findings suggest that the simultaneous detection of serum‐derived exosomal PIK3CAH1047R mutation and serum IL6 secretion may serve as a promising diagnostic and prognostic tool for CRC and simultaneous targeting of PIK3CAH1047R mutation and IL6 may serve as a novel approach for the treatment of CRC.

Background Endoscopic ultrasound (EUS) is one of the most accurate methods for determining the originating layer of subepithelial lesions (SELs). However, the accuracy is greatly influenced by the expertise and proficiency of the endoscopist. In this study, we aimed to develop an artificial intelligence (AI) model to identify the originating layer of SELs in the esophagus and evaluate its efficacy. Methods A total of 1445 cases of esophageal SELs were used to develop the model. An AI model stemming from YOLOv8s-seg and MobileNetv2 was developed to detect esophageal lesions and identify the originating layer. Two seniors and two junior endoscopists independently diagnosed the same test set. Results The precision, recall, mean average precision @ 0.5, and F1-score of the AI model were 92.2%, 73.6%, 0.832, and 81.9%, respectively. The overall accuracy of the originating layer recognition model was 55.2%. The F1-scores of the second, third, and fourth layers were 47.1%, 51.7%, and 66.1%, respectively. The accuracy of the AI system in differentiating layers 2 and 3 from four was 76.5% and was similar to that of senior endoscopists (74.9–79.8%, P = 0.585) but higher than that of junior endoscopists (65.6–66.7%, P = 0.045). Conclusions The EUS-AI model has shown high diagnostic potential for detecting esophageal SELs and identifying their originating layers. EUS-AI has the potential to enhance the diagnostic ability of junior endoscopists in clinical practice. Graphical abstract

Background With the increase in risk factors and the emergence of unhealthy lifestyles in young adults, we need to pay more attention to the cardiovascular health of this group. This study aimed to assess the association of the degree of joint risk factor control with premature cardiovascular disease (CVD) and all-cause mortality in young people. Methods Kailuan Study is a prospective cohort study based on a community population, which began in June 2006, and followed up every two years. A sample of 16,519 eligible participants in the Kailuan cohort was recruited in this current study and 15,948 was included in the final analysis, with an average age of 32.34 ± 5.19 years, and a male proportion of 74.76%. Based on the control status of the risk factors, participants were divided into three groups: well-controlled group (≥ 7 risk factors controlled), moderately controlled group (5–6 risk factors controlled), and poorly controlled group (≤ 4 risk factors controlled). Multivariate Cox proportional hazard model was used to analyse the relationship between the joint control of risk factors and onset of CVD and all-cause mortality. Results During a mean follow-up period of 14.78 ± 1.33 years, we identified 285 incident CVD cases and a total of 274 deaths from all causes. Compared to the well-controlled group, the moderately controlled group and poorly controlled group exhibited progressively higher risks of CVD and all-cause mortality. The adjusted hazard ratios (HRs) for CVD in the moderately controlled group and poorly controlled group were 2.24 (95% confidence interval [CI]: 1.66–3.02) and 3.09 (95% CI: 2.04–4.68), respectively. The adjusted HRs for all-cause mortality in these two groups were 1.53 (1.15–2.04) and 2.65 (1.79–3.92), respectively. Conclusions We observed an inverse relationship between the degree of risk factor control and the risk of CVD and all-cause mortality in young adults, emphasizing the importance of actively controlling more risk factors in early life.

Aims To verify the influence of glucagon-like peptide-1 receptor agonists (GLP-1 RA) on renal function parameters in type 2 diabetes based on well-known randomized controlled trials (RCTs). Methods PubMed, Cochrane, Web of Science, Embase, and grey literature were searched for RCTs published until December 24, 2024. The quality of the RCTs was assessed using the Cochrane risk-of-bias tool. Weighted mean differences (WMD) and 95% confidence intervals (CIs) were calculated for continuous variables using meta-analysis. The primary outcomes were composite renal function parameters, including serum creatinine (Cr) levels, estimated glomerular filtration rate (eGFR), urinary albumin excretion (UAE), and urinary albumin-to-creatinine ratio (UACR). Results Pooled data from 24 studies revealed that GLP-1 RA positively influenced renal outcomes in the type 2 diabetes group to some extent compared with that in the control group. GLP- 1 RA decreased serum creatinine levels (WMD=-0.10, 95%CI -0.19 to -0.01, I² = 33%, P < 0.05), eGFR(WMD = 0.54, 95% CI 0.19 to 0.90, I² = 27%, P < 0.05), UAE (WMD=-11.92, 95% CI − 23.50 to − 0.33, I² = 0%, P < 0.05) and UACR (WMD: −1.01 mg/g, 95% CI:−1.68, -0.34, I² = 15%, P < 0.05) in the type 2 diabetes group. Conclusion GLP-1 RA treatment significantly elevated eGFR, decreased the UACR, and positively influenced renal function outcomes in the type 2 diabetes group. Clinical trial number Not applicable.

The exhausted CD8 ⁺ T (T EX ) cells consist of distinct subsets including Tcf1 ⁺ stem-like, Tcf1 – Cx3cr1 ⁺ intermediate (T EX -int) and Tcf1 – Cx3cr1 – terminally exhausted cells; yet, epigenetic determinants of T EX subset differentiation remain incompletely understood. Using chronic viral infection, we show that histone deacetylase 1 (Hdac1) was specifically required for the formation of antigen-specific T EX -int cells at the effector phase of responses. Single-cell transcriptomics validated that Hdac1 deficiency depleted T EX -int cells and revealed that Hdac1 was critical for positive regulation of T EX -int-characteristic genes, including Cx3cr1 , Cxcr6 , and Klf2 . Furthermore, profiling chromatin accessibility landscape in T EX subsets demonstrated that loss of Hdac1 resulted in a prevalent increase in chromatin open state, as evidently observed at the exhaustion program genes, which were linked to induced expression of exhaustion-inducing Tox transcription factor, PD1 and Lag3 coinhibitory receptors in T EX cells. Hdac1 thus has dual regulatory functions: promoting T EX -int cell fate and preventing excessive activation of the exhaustion program to curtail uncontrolled virus replication.

Background: Plant-based diets are generally considered to be associated with a decreased risk of several chronic diseases. However, there is limited prospective evidence on the association between plant-based diet quality...

Enhancer of zeste homolog 2 (EZH2), a protein encoded by the EZH2 gene, is a crucial subunit in polycomb repressive complex 2. EZH2 controls the transcription of genes critical for cell proliferation, differentiation, amplification, and function through both methylated and unmethylated functions. EZH2 is considered to be a transcriptional suppressor protein when it controls histone methylation. Its dysregulation is related to a variety of cancers, with significant evidence showing its role in prostate cancer and breast cancer. EZH2 is also thought to be involved in the differentiation and function of immune cells. Ongoing research on EZH2 has revealed the correlation between inflammatory nasal diseases, the occurrence and development of nasal sinus tumors, and EZH2. This article aimed to review the research progress on the role of EZH2 in nasal diseases and explore the possibility of future EZH2-targeted therapies for nasal diseases.

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as nonalcoholic fatty liver disease (NAFLD), affects approximately 30% of adults worldwide. Approximately 1/6 of MASLD patients progress to metabolic dysfunction-associated steatohepatitis (MASH) and potentially evolve towards cirrhosis and hepatocellular carcinoma (HCC). This condition imposes a significant burden on the global health. Although MASH is primarily a metabolic disorder, immune cells play a crucial role in its development. The activation of immune cells involves alterations in transcription and protein synthesis, which require metabolic adaptation of cellular substrate metabolism, including glucose and lipid metabolism. Moreover, the lipid-rich environment of the liver can affect the metabolism of immune cells. In this review, we delineate the metabolic profiles of immune cells in MASH, focusing on macrophages and T cells, and discuss the impact of targeting cellular metabolism on these cells along with clinical trial outcomes. Macrophages in MASH are characterized by increased glycolysis, compromised oxidative phosphorylation, and augmented lipid uptake, synthesis, and fatty acid oxidation, all of which contribute to their inflammatory phenotype. Lymphocytes, such as T cells and NK cells, exhibit impaired metabolic functions that hamper their immune surveillance capabilities and facilitate the development of HCC. However, research on the metabolic characteristics of other types of immune cells remains limited. With the development of single-cell genomics and animal models of MASH, we anticipate that further studies in this compelling field may shed light on the pathogenesis of MASH and pave the way for novel therapeutic strategies.

The rapid advancement of wearable technology has led to the growing significance of flexible sensors in medical health monitoring and motion tracking. Traditional electronic skin frequently experiences unstable sensing performance attributed to inadequate interface compatibility and uneven distribution of conductive materials. Ionic skin presents an innovative method for acquiring biological signals via ion migration; however, its biocompatibility concerns restrict its broader use. This study introduces an eco‐friendly and efficient synthetic method for the preparation of conductive elastomers utilizing deep eutectic solvents (DES) and polyvinyl alcohol (PVA). The resulting composite polymer network structure demonstrates a balance between elevated mechanical strength and high conductivity. The resultant material exhibits an electrical conductivity of 4.4 × 10⁻¹ S m⁻¹ and a tensile strain of 1200%. The attributes of this elastomer allow pressure sensors to demonstrate exceptional performance, featuring a sensitivity of 0.21 kPa⁻¹ and a wide detection range of 0–200 kPa. This research presents a novel approach for the development of high‐performance flexible sensing materials, which hold considerable application potential in areas including healthcare and motion detection.