With the continuous deepening of the concept of precision diagnosis and treatment for lung cancer, how to achieve higher efficiency and accuracy in the screening, diagnosis, and treatment pathways in clinical practice has become an important issue that urgently needs to be overcome. The current clinical difficulty lies in the fact that despite continuous advancements in imaging and molecular diagnostic technologies, there are still limitations in manual efficiency and subjective experience when it comes to massive data analysis and multi-scale feature extraction. Artificial intelligence (AI), especially algorithm systems based on deep learning, is an innovative technology capable of deeply empowering medical big data. This method utilizes algorithms such as convolutional neural networks, combined with radiomics, pathomics, and multi-modal data fusion analysis, demonstrating immense potential in early precise detection and benign-malignant differentiation of pulmonary nodules, digital pathological subtype recognition and non-invasive prediction of driver genes, precise 3D surgical planning and automatic delineation of radiotherapy target volumes, as well as dynamic risk warning during follow-up. This innovative technology provides a brand-new solution for realizing intelligent and individualized lung cancer diagnosis and treatment models. This consensus, based on the latest evidence from evidence-based medicine and combined with the development trends in the AI field and real-world clinical needs, was ultimately formed by gathering the consensus opinions of multidisciplinary experts in radiology, pathology, thoracic surgery, and other fields. The main content covers the application specifications of AI in the three core scenarios of lung cancer screening, diagnosis, and treatment, the technical standards for data collection and algorithm validation, as well as the ethical and regulatory challenges faced at the current stage. It aims to clarify the applicable boundaries of AI as a clinical auxiliary decision support tool, providing scientific guidance and standardized exploration directions for peers currently engaged in or planning to carry out AI-assisted clinical diagnosis, treatment, and translation of lung cancer.

Tumor angiogenesis is a core pathological driver of malignant growth, invasion, and metastasis, and represents a major obstacle to effective anticancer therapy. Conventional antiangiogenic agents, including neutralizing monoclonal antibodies and small-molecule tyrosine kinase inhibitors, are constrained by drug resistance, on-target toxicity, and the compensatory activation of alternative pro-angiogenic pathways. Targeted protein degradation (TPD) has emerged as a promising strategy that may overcome these limitations. Unlike traditional inhibitors that operate through an occupancy-driven mechanism, degraders function through an event-driven catalytic mechanism in which a single degrader molecule can catalytically promote the ubiquitination and subsequent proteasomal or lysosomal degradation of multiple molecules of the same target protein, thereby eliminating the target protein together with all of its functions rather than merely blocking a single active site. This review systematically delineates the pathophysiological basis of tumor angiogenesis, encompassing the angiogenic switch driven by hypoxia-inducible factor-1α (HIF-1α), the aberrant structural and functional features of the tumor vasculature, and the self-reinforcing vicious cycles that sustain malignant progression. We then categorize the principal TPD modalities, with particular emphasis on proteolysis-targeting chimeras (PROTACs) and lysosome-targeting chimeras (LYTACs), and describe their design principles and mechanisms of action. PROTACs recruit E3 ubiquitin ligases to direct intracellular targets to the ubiquitin-proteasome system for degradation, whereas LYTACs engage lysosome-targeting receptors to route extracellular and membrane proteins to the lysosome, thereby expanding the degradable target space beyond the intracellular proteome. We further summarize recent advances in the application of TPD to antiangiogenic intervention at four distinct levels. First, at the signaling initiation level, degradation of vascular endothelial growth factor (VEGF) and its receptor vascular endothelial growth factor receptor 2 (VEGFR2) by aptamer-engineered PROTACs, antibody-based LYTACs, and small-molecule VEGFR2 degraders blocks the upstream trigger of the angiogenic cascade. Second, at the signal transduction level, degradation of focal adhesion kinase (FAK), B-Raf proto-oncogene serine/threonine kinase (BRAF), phosphodiesterase 4 (PDE4), and bromodomain-containing protein 4 (BRD4) interrupts intracellular signaling cascades and transcriptional responses. Third, at the microenvironment level, degradation of proviral integration site for Moloney murine leukemia virus (PIM) kinases curtails the pro-angiogenic signals secreted by tumor-associated macrophages. Fourth, multi-target synergistic strategies, exemplified by bispecific degraders that simultaneously target human epidermal growth factor receptor 2 (HER2) and VEGF-A, represent a preliminary exploration of cooperative intervention. Representative degraders reviewed herein elicit diverse antiangiogenic phenotypes, ranging from the direct inhibition of endothelial cell proliferation, migration, and tube formation to reductions in microvessel density and the suppression of vasculogenic mimicry. Finally, we discuss the major challenges that remain, including the precise matching of degradation kinetics with the vascular normalization window, target selectivity and tissue specificity, and the activation of compensatory networks and the emergence of resistance. Since the application of TPD in this setting remains at an early stage, the clinical translation of these approaches will require careful optimization of degradation efficiency, spatiotemporal control, and delivery strategies. We also envision future directions toward immunotherapy-based combination regimens and precision-degradation approaches guided by single-cell and spatial transcriptomics. In our view, TPD should not be regarded merely as a substitute for conventional antiangiogenic drugs, but rather as a molecular tool capable of systematically remodeling the tumor vascular microenvironment. When precise control of degradation efficiency and spatiotemporal regulation are integrated with a thorough understanding of the heterogeneity and compensatory capacity of tumor vessels, the full clinical potential of this strategy can be realized.

T7 RNA polymerase (T7 RNAP) is one of the simplest known RNA polymerases. Its unique structural features make it a critical model for studying the mechanisms of RNA synthesis. This review systematically examines the static crystal structure of T7 RNAP, beginning with an in-depth examination of its characteristic “thumb”, “palm”, and “finger” domains, which form the classic “right-hand-like” architecture. By detailing these structural elements, this review establishes a foundation for understanding the overall organization of T7 RNAP. This review systematically maps the functional roles of secondary structural elements and their subdomains in transcriptional catalysis, progressively elucidating the fundamental relationships between structure and function. Further, the intrinsic flexibility of T7 RNAP and its applications in research are also discussed. Additionally, the review presents the structural diagrams of the enzyme at different stages of the transcription process, and through these diagrams, it provides a detailed description of the complete transcription process of T7 RNAP. By integrating structural dynamics and kinetics analyses, the review constructs a comprehensive framework that bridges static structure to dynamic processes. Despite its advantages, T7 RNAP has a notable limitation: it generates double-stranded RNA (dsRNA) as a byproduct. The presence of dsRNA not only compromises the purity of mRNA products but also elicits nonspecific immune responses, which pose significant challenges for biotechnological and therapeutic applications. The review provides a detailed exploration of the mechanisms underlying dsRNA formation during T7 RNAP catalysis, reviews current strategies to mitigate this issue, and highlights recent progress in the field. A key focus is the semi-rational design of T7 RNAP mutants engineered to minimize dsRNA generation and enhance catalytic performance. Beyond its role in transcription, T7 RNAP exhibits rapid development and extensive application in fields, including gene editing, biosensing, and mRNA vaccines. This review systematically examines the structure-function relationships of T7 RNAP, elucidates the mechanisms of dsRNA formation, and discusses engineering strategies to optimize its performance. It further explores the engineering optimization and functional expansion of T7 RNAP. Furthermore, this review also addresses the pressing issues that currently need resolution, discusses the major challenges in the practical application of T7 RNAP, and provides an outlook on potential future research directions. In summary, this review provides a comprehensive analysis of T7 RNAP, ranging from its structural architecture to cutting-edge applications. We systematically examine: (1) the characteristic right-hand domains (thumb, palm, fingers) that define its minimalistic structure; (2) the structure-function relationships underlying transcriptional catalysis; and (3) the dynamic transitions during the complete transcription cycle. While highlighting T7 RNAP’s versatility in gene editing, biosensing, and mRNA vaccine production, we critically address its major limitation—dsRNA byproduct formation—and evaluate engineering solutions including semi-rationally designed mutants. By synthesizing current knowledge and identifying key challenges, this work aims to provide novel insights for the development and application of T7 RNAP and to foster further thought and progress in related fields.

Objective To investigate the expression of serum tumor-associated antigens(TAAs)in patients with rheumatoid arthritis(RA)and analyze their clinical significance for RA.Methods A total of 214 RA patients were enrolled in the RA group,while 198 age-and gender-matched healthy individuals were included in the HC group.Rheumatoid factor(RF),anti-cyclic citrullinated peptide antibody(Anti-CCP),C-reactive protein(CRP),erythrocyte sedimentation rate(ESR),interleu-kin-6(IL-6),ferritin levels,as well as gender,age,disease duration,disease activity score(DAS28)and clinical manifestations were collected from the RA group.The expression of TAAs in RA patients and the clinical characteristics of TAA-positive patients were analyzed.Spearman correla-tion analysis was used to evaluate the relationships between TAAs and clinical indicators in RA pa-tients.Results The positive rate of carbohydrate antigen 125(CA125)in the RA group was 8.88％,which was significantly higher than 1.01％ in the HC group(P＜0.001).Serum CA125 and cytok-eratin fragment 19(CYFRA21-1)levels in the RA group were significantly higher than those in the HC group,whereas alpha-fetoprotein(AFP),carcinoembryonic antigen(CEA),carbohydrate anti-gen 199(CA199)and neuron-specific enolase(NSE)levels were significantly lower(P＜0.001).TAA-positive patients had significantly older age and higher rates of pulmonary interstitial lesions compared to TAA-negative patients(P＜0.05).Patients with DAS28 scores＞5.1 had significantly higher CA125 levels than those with DAS28 scores ≤5.1(P＜0.05).CA125 levelswere positively corre-lated with DAS28 scores,ESR,RF,and anti-CCP antibodies(r=0.142,0.140,0.268,0.183;P＜0.05).Conclusion In RA patients,the positivity rate and levels of some serum TAAs are ele-vated,and TAA-positive patients tend to be older and have higher incidence of pulmonary interstitial lesions.CA125 levels are positively correlated with RA disease activity.

Objective To explore the application of plasma 7 microRNA (miR7) testing in the differential diagnosis of very early-stage hepatocellular carcinoma (HCC). Methods This study is a multicenter real-world study. Patients with single hepatic lesion (maximum diameter≤2 cm) who underwent plasma miR7 testing at Zhongshan Hospital, Fudan University, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Anhui Provincial Hospital, and Peking University People’s Hospital between January 2019 and December 2024 were retrospectively enrolled. Patients were divided into very early-stage HCC group and non-HCC group, and the clinical pathological characteristics of the two groups were compared. The value of plasma miR7 levels, alpha-fetoprotein (AFP), and des-gamma-carboxy prothrombin (DCP) in the differential diagnosis of very early-stage HCC was evaluated using receiver operating characteristic (ROC) curves and area under the curve (AUC). In patients with both negative AFP and DCP (AFP＜20 ng/mL, DCP＜40 mAU/mL), the diagnostic value of plasma miR7 for very early-stage HCC was analyzed. Results A total of 64 528 patients from 4 hospitals underwent miR7 testing, and 1 682 were finally included, of which 1 073 were diagnosed with very early-stage HCC and 609 were diagnosed with non-HCC. The positive rate of miR7 in HCC patients was significantly higher than that in non-HCC patients (67.9% vs 24.3%, P＜0.001). ROC curves showed that the AUCs for miR7, AFP, and DCP in distinguishing HCC patients from the non-HCC individuals were 0.718, 0.682, and 0.642, respectively. The sensitivities were 67.85%, 43.71%, and 44.45%, and the specificities were 75.70%, 92.78%, and 83.91%, respectively. The pairwise comparison of AUCs showed that the diagnostic efficacy of plasma miR7 detection was significantly better than that of AFP or DCP (P＜0.05). Although its specificity was slightly lower than AFP and DCP, the sensitivity was significantly higher. Among patients negative for both AFP and DCP, miR7 maintained an AUC of 0.728 for diagnosing very early-stage HCC, with 67.82% sensitivity and 77.73% specificity. Conclusions Plasma miR7 testing is a potential molecular marker with high sensitivity and specificity for the differential diagnosis of small hepatic nodules. In patients with very early-stage HCC lacking effective molecular markers (negative for both AFP and DCP), miR7 can serve as a novel and effective molecular marker to assist diagnosis.

As an indispensable trace element in the human body,copper plays an important role in various physiological and biochemical reactions.The dyshomeostasis of copper leads to the disorder of copper metabolism and the occurrence of related diseases.Cuproptosis,a newly proposed regulatory cell death mode,is different from the known apoptosis,pyroptosis,necroptosis,and ferroptosis.Recent studies have found that the dyshomeostasis of copper has been observed in a variety of cancers.Therefore,targeting copper for disease treatment may become a new strategy and a new idea.This article systematically summarizes the fundamental properties of copper,copper dyshomeostasis-related diseases (Menkes syndrome,Wilson's disease,and cancer) and their treatment,and reviews the research progress in cuproptosis.
Humans ; Copper/metabolism* ; Homeostasis ; Neoplasms/metabolism* ; Hepatolenticular Degeneration/metabolism* ; Menkes Kinky Hair Syndrome/metabolism*

Objective This study investigated feasible cases and their significance in promoting the"generalized"development of inspection through digital-intelligent equipment.Methods A qualitative research approach was used,involving interviews conducted between February 2025 and March 2025 with experts in traditional Chinese medicine diagnostics,clinical research methodology,medical engineering integration,and related disciplines,using both online and offline methods.In accordance with the Consolidated Criteria for Reporting Qualitative Research,feasible cases involving the specific application of digital equipment in various parts of observation were collected through item enrichment.The significance of extending observation capabilities via these cases was analyzed,along with the overall implications of integrating digital technologies with traditional inspection method.Results Interviews were completed with 11 experts from domestic universities and research institutes in the fields of traditional Chinese medicine diagnosis,medical engineering integration,and related disciplines.A total of 78 feasible cases of digital-intelligent inspection were identified,along with 69 insights regarding the significance of enhancing the inspection capabilities.These insights were synthesized into two dimensions and 23 holistic meanings.The first dimension is to expand the scope of inspection,including obtaining internal environmental characteristics,observing external environmental characteristics,expanding thermodynamic characteristic data,and crossing time and space.The second dimension is to improve the quality of observation and diagnosis information collection and analysis,including 19 specific meanings,such as standardized collection environment,objective quantification,and refined observation.Conclusion Digital-intelligent equipment plays a significant role in expanding the scope of inspection content and achieving high-quality acquisition and analysis of extensive inspection information.These advancements extend and enrich the capabilities of traditional inspection method in traditional Chinese medicine.

Objective:To investigate the acute effects of persistent high exposure to atmospheric fine particulate matter (PM 2.5) on residents' outpatient visits for respiratory diseases. Methods:We collected daily outpatient records from 92 hospitals in 13 cities across the Beijing-Tianjin-Hebei region, along with daily PM 2.5, nitrogen dioxide (NO 2), and meteorological data from 2013 to 2018. Five persistent high PM 2.5 exposure scenarios were defined in terms of daily mean PM 2.5 concentrations (>75 μg/m 3 and >150 μg/m 3), duration (≥2 days and ≥3 days), and whether or not there was concurrent exposure to high levels of NO 2 (daily mean NO 2 concentration >50 μg/m 3). A two-stage statistical analysis strategy based on a generalized linear model was applied to conduct a time-series analysis to assess the exposure-response relationship between persistent high PM 2.5 exposure scenarios and residents' outpatient visits for a variety of respiratory diseases, and to estimate excess outpatient visits. Results:During the period, M ( Q1, Q3) PM 2.5 and NO 2 concentrations were 61.2 (42.3, 95.1) μg/m 3 and 40.2 (31.4, 54.4) μg/m 3, respectively, and the daily respiratory disease outpatient visits were 57 (52, 66) cases. When compared with non-permanent high PM 2.5 exposure periods, exposure scenarios with PM 2.5 >75 μg/m 3 and lasting for ≥2 days caused an increased risk of outpatient visits for respiratory diseases by 2.10% (95% CI: 1.44%-2.77%), and resulted in 43 787 (95% CI: 30 025-57 757) excess visits; in this scenario, the concurrent exposure to high levels of NO 2 had a greater acute effect on respiratory disease visits than the absence of exposure to high levels of NO 2 ( P<0.001). The risk of respiratory disease visits increased substantially by 4.41% (95% CI: 3.15%-5.68%) when the daily mean PM 2.5 concentration exceeded 150 μg/m 3 for ≥2 days. Subgroup disease analyses showed that scenarios with daily mean PM 2.5 concentrations exceeding 75 μg/m 3 for ≥3 days caused a significant increase in the risk of lower respiratory tract infections, chronic lower respiratory disease, and asthma visits. Conclusions:Sustained persistent high PM 2.5 exposure increases the risk of outpatient visits for various respiratory diseases; concurrent exposure to high concentrations of NO 2 leads to a greater risk of visiting the clinic, suggesting that the prevention and control of PM 2.5 pollution should be synchronized with the control of mobile source emissions, to synergistically manage the compound pollution of PM 2.5 and NO 2 in the atmosphere.

Purpose To investigate the relationship between the expression of POSTN and NECTIN-3 in urothelial carcinoma(UC)and its clinicopathologic features and prognosis.Methods Clinical data of 115 UC patients were col-lected.EnVision two-step method was used for immunohistochemical analysis to determine the expression of POSTN and NECTIN-3 in UC and their correlation with clinicopathological features and prognosis.Transcriptomic data from TCGA database were used to analyze the correlation between the expression of POSTN and NECTIN-3 in bladder cancer and the pathological stage and prognosis of bladder cancer.qPCR and Western blot were used to detect the expression levels of POSTN and NECTIN-3 in tumor tissues and adjacent tissues of patients.Results TCGA database analysis showed that the expression level of NECTIN-3 in urinary bladder urothelial carcinoma(UBUC)was significantly lower than that in paracancer tissues,and POSTN expression was positively correlated with pathological stage.Prognostic a-nalysis showed that POSTN expression was negatively correlated with the overall survival of UBUC(P＞0.05),and NECTIN-3 expression was negatively correlated with disease-free survival of UBUC(P＞0.05).The experimental re-suits showed that patients with positive POSTN expression were more prone to perineural invasion[25 cases(86.2％)vs 4 cases(13.8％),P=0.019],vascular invasion[36 cases(83.7％)vs 7 cases(16.3％),P=0.007],and lymph node metastasis[24 cases(88.9％)vs 3 cases(11.1％),P=0.033].Additionally,the positive expression rate of POSTN in UBUC was significantly higher than that in upper tract urothelial carcinoma(UTUC)(75.0％vs 54.3％,P=0.028).Higher expression levels of POSTN and NECTIN-3 were associated with shorter overall survival,but the difference was not statistically significant(P＞0.05).Conclusion There is no significant correlation between NECTIN-3 and the clinicopathological features and prognosis of urothelial carcinoma,while the expression of POSTN is correlated with the invasive clinicopathological features of UC,which has certain suggestive significance for clinical stage and prognosis.

Traditional Chinese medicine(TCM) capable of clearing heat and removing toxin is most commonly used in clinical practice and has the effect of removing fire-heat and toxin. Studies have shown that most of the Ilex plants have the effect of clearing heat and removing toxin, among which the varieties of I. cornuta, I. pubescens, I. rotunda, I. latifolia, and I. chinensis are most widely used. These plants generally contain triterpenoids and their glycosides, alkaloids, flavonoids, phenylpropanoids, and other chemical components, especially pentacyclic triterpenoids. According to their skeletons, pentacyclic triterpenoids can be divided into the oleanane type, the ursane type, the lupinane type, etc. Among them, ursane-type components are the most abundant, and 136 species have been found so far. These components have been proved to have pharmacological effects such as anti-inflammatory, anti-tumor, hypolipidemic, anti-thrombosis, cardiomyocyte-protective, antibacterial, and hepatoprotective effects. Therefore, this paper systematically reviews the domestic and foreign literature on Ilex plants with a focus on the research progress on pentacyclic triterpenoids and their pharmacological activities, aiming to provide reference for the development of TCM resources with the effect of clearing heat and removing toxin.
Ilex/chemistry* ; Plants, Medicinal/chemistry* ; Pentacyclic Triterpenes/pharmacology* ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/pharmacology* ; Humans ; Animals