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.

Nowadays, lung cancer is the most common and lethal invasive tumor type in Chinese population, challenging overall health level. However, personalized early-stage treatment is currently still not widely implemented, and the choice of treatment highly depends on experience of physician. Based on deep learning and radiomics principles, deep-radiomics is important for establishing objective and promotable precision medicine plans. Among all aspects, the explainability of a model is critical for its usage in clinical practice. This paper discusses the technical aspects of explainable deep-radiomics in lung cancer, and analyzes challenges we are facing. Non-fully supervised learning methods, as a current hotspot in deep learning technology, can construct more trustworthy and practically valuable deep learning models through the co-design method of performance-interpretability. Medical artificial intelligence faces three core challenges in transitioning from the laboratory to hospitals: high-level cognitive demands, data privacy and generalization capabilities, and regulatory compliance. However, with appropriate design, non-fully supervised learning holds the greatest potential to bridge the gap between design and application, enabling broader adoption.

This study aimed to investigate the mechanism of liquiritin (LQ) in the improvement of ventricular remodeling (VR) after acute myocardial infarction (AMI). Molecular docking was used to predict the binding affinity of liquiritin to thioredoxin-interacting protein (TXNIP). After 2 weeks of modeling, the rats were randomly divided into a model group, a low-dose liquiritin group (20 mg/kg LQ), and a high-dose liquiritin group (40 mg/kg LQ). Liquiritin was administered by gavage once a day, and the sham group and model group were given the same volume of 0.5% sodium carboxymethylcellulose (CMC-Na), with intervention of 4 consecutive weeks. Echocardiography was employed to detect the cardiac function, HE staining was used to observe cardiological changes, ELISA was used to detect the activity of serum creatine kinase-MB (CK-MB) activity, and the colorimetric method was adopted to detect serum malondialdehyde (MDA), total superoxide dismutase (T-SOD) and catalase (CAT) activities. RT-qPCR was used to detect the gene expressions of TXNIP, thioredoxin (TRX) and NACHT, LRR, and PYD domains-containing protein 3(NLRP3). Western blot was used to detect the protein expressions of TXNIP, TRX and NLRP3 in rat myocardial tissue. Molecular docking results showed that liquiritin had a good binding affinity to TNXIP target. After 20 and 40 mg/kg liquiritin intervention, the levels of ejection fraction (EF) and fractional shortening (FS) were significantly increased (P<0.01), and the levels of LVIDs, LVIDd, LVESV, and LVEDV were decreased (P<0.01). The myocardial structure was significantly improved, the cell arrangement tended to be regular, and the area of inflammatory cell infiltration and necrosis was reduced. Liquiritin significantly reduced the level of CK-MB (P<0.01), decreased the activity of MDA, and increased the activities of CAT and T-SOD (P<0.01). Liquiritin effectively inhibited the overexpression of TXNIP and NLRP3 genes and proteins, and enhanced the expression of TRX genes and proteins in the myocardial tissues of AMI rats. In conclusion, liquiritin has a regulatory effect on the TXNIP/TRX signaling pathway, inhibits the activation of the NLRP3 inflammasome, and thus improves ventricular remodeling after acute myocardial infarction.

Objective To summarize 20 years' clinical experience of urethroplasty with pedicled tunica vaginalis grafts in the treatment of long-segment anterior urethral stricture (＞2 cm) caused by male genital lichen sclerosus (GLSc). Methods A retrospective study was conducted on the clinical data of 90 patients undergoing urethroplasty with pedicled tunica vaginalis grafts in our hospital. Patients were divided into three groups according to the length of stricture: 4-7 cm (n=25), ＞7-10 cm (n=44), and＞10 cm (n=21). The surgical conditions, changes in preoperative and postoperative maximum urinary flow rate (Qmax), and improvements in the international index of erectile function (IIEF-5) scores were compared among the three groups. Results During the follow-up of 6-48 (average 22.0±2.7) months, 88 patients exhibited unimpeded urination, with a success rate of 97.8%. Retrograde urethrography showed the urethral lumen was well-dilated, the penis was not deformed or strictured, and the sexual intercourse was normal. The Qmax of the three groups was significantly improved 2, 6 and 12 months postoperatively (P＜0.01), but with no statistically significant differences among the three groups (P＞0.05). Similarly, the IIEF-5 scores showed no statistically significant differences among or within the groups (P＞0.05). No serious complications occurred after operation. Urethral stricture occurred in 2 cases after operation, one of which had smooth urination after holmium laser urethrotomy, and the other achieved urination after anterior urethral incision. Conclusion Urethroplasty with pedicled tunica vaginalis grafts is suitable for the treatment of long-segment anterior urethral stricture caused by GLSc. It has the advantages of high surgical success rate, convenient graft harvesting, simple operation, few trauma and few complications. This surgical approach is recommended for primary hospitals.

With the aging population and the widespread implementation of lung cancer screening programs, an increasing number of elderly patients are undergoing curative lung resection. Due to diminished physiological reserve and complex comorbidities, this demographic exhibits a significantly higher incidence of severe perioperative complications (defined as Clavien-Dindo grade≥Ⅲ), which adversely affects both perioperative safety and long-term prognosis. In recent years, the research paradigm has shifted from univariate analysis toward multidimensional risk integration and the development of predictive models. This article systematically reviews the key risk factors for severe perioperative complications in elderly lung cancer patients, encompassing biological aging processes, frailty and sarcopenia, cardiopulmonary and renal functional reserves, inflammatory-immune and coagulation status, and perioperative interventions. Furthermore, it traces the evolution of risk assessment tools from traditional regression models to machine learning models that integrate multimodal data. The review also discusses common challenges in this field, including the standardization of outcome definitions, external validation, calibration assessment, and clinical translation. Future efforts should prioritize the deep integration of predictive tools with clinical decision support systems to establish a closed-loop care pathway from risk identification to stratified intervention, thereby effectively reducing complication rates and enhancing surgical outcomes for elderly lung cancer patients.

[摘 要] 目的：探讨含溴结构域蛋白1（BRD1）通过调控PI3K/AKT信号通路影响非小细胞肺癌（NSCLC）进展的作用机制。方法：利用TIMER 3.0数据库评估BRD1作为免疫治疗标志物的预测价值。利用慢病毒体系构建稳定过表达BRD1及N端截短突变体BRD1-ΔN的人肺癌细胞A549和NCI-H1299。采用CCK-8实验、克隆形成实验、划痕愈合实验及Transwell实验检测过表达BRD1/BRD1-ΔN对细胞增殖和迁移能力的影响；流式细胞术和Western blotting检测细胞凋亡水平及凋亡相关蛋白的变化。RNA-seq筛选受BRD1/BRD1-ΔN影响的信号通路，Western blotting及体外激酶实验验证BRD1/BRD1-ΔN过表达对AKT磷酸化的调控作用。采用AKT抑制剂LY294002处理过表达BRD1/BRD1-ΔN的NCI-H1299细胞，结合功能实验（CCK-8实验、划痕愈合实验）明确过表达BRD1/BRD1-ΔN促进细胞的增殖和迁移是否依赖AKT活化。通过RNA-seq联合KEGG/GSEA分析、免疫共沉淀（Co-IP）、RT-qPCR，鉴定整合素α2（ITGA2）是促进AKT活化的关键分子；通过Co-IP、敲低ITGA2、Western blotting及功能实验明确ITGA2在BRD1调控AKT活化中的具体作用。结果：数据库分析显示，BRD1可作为NSCLC免疫治疗的中等预测标志物（AUC = 0.625）。过表达BRD1/BRD1-ΔN显著增强了NSCLC细胞的增殖和迁移能力（P < 0.01或P < 0.001），但不影响细胞凋亡及凋亡相关蛋白的表达（均P > 0.05）；RNA-seq分析表明过表达BRD1/BRD1-ΔN主要富集于PI3K/AKT信号通路。Western blotting及体外激酶实验显示，BRD1/BRD1-ΔN过表达不影响AKT上游激酶（PDK1）的磷酸化，也不改变AKT的乙酰化修饰水平（均P > 0.05）；AKT抑制剂LY294002处理过表达BRD1/BRD1-ΔN细胞，发现BRD1/BRD1-ΔN促细胞增殖和迁移的作用部分依赖AKT的活化；RT-qPCR及Western blotting证实，BRD1过表达可上调ITGA2的mRNA和蛋白水平，敲低ITGA2则可逆转BRD1诱导的AKT激活及细胞增殖和迁移能力的增强。结论：BRD1是NSCLC的一种新型促癌因子，其通过上调ITGA2表达激活AKT信号通路，进而促进肺癌细胞的增殖和迁移。

Alacrima-achalasia-mental retardation syndrome(AAMR) is an extremely rare autosomal recessive genetic disorder caused by mutation in the GMPPA gene. Its pathogenesis is associated with congenital disorders of glycosylation. The clinical manifestations involve multiple system impairments, with alacrima, achalasia, and mental retardation as the core features. This article reports the diagnosis, treatment process and long-term follow-up outcomes after deep brain stimulation in one patient with AAMR complicated with dystonia, aiming to improve clinicians' understanding of this disease.

Although global brain science research has progressed rapidly in recent decades, several fundamental questions in neuroscience remain unresolved. In particular, the physical mechanism underlying neural signal transmission remains controversial, and the carriers responsible for neural information storage and retrieval have not yet been fully clarified. These unresolved issues motivate us to re-examine the processes of neural information generation, transmission, integration, storage, and retrieval from multiple perspectives. A key observation is that neural electromagnetic activities are closely associated with time. Their duration, temporal structure, and dynamic evolution play crucial roles in neural information processing. In this work, we analyze neural electromagnetic activities from the perspective of temporal scales (referred to here as the “time course”). By reviewing and integrating findings from previous studies, we examine the characteristic time requirements and dynamic features of neural processes occurring at different stages of information processing. These stages include neural signal generation, signal transmission along axons, synaptic integration, synaptic plasticity, and memory formation and retrieval. Based on this temporal analysis, we outline a framework describing neural electromagnetic activities across a wide range of time scales, spanning from microseconds to minutes, hours, or even longer periods associated with long-term memory, which suggests that neural information processing involves multiple physical processes operating at different time levels. Rapid electromagnetic events may occur on microsecond scales, whereas electrophysiological phenomena such as action potentials typically last on the order of milliseconds. Longer time scales are associated with synaptic plasticity and memory-related processes. From this perspective, we propose that the physical carrier of neural information may be transient electromagnetic pulses with durations on the microsecond scale. In this framework, action potentials can be interpreted as the macroscopic electrophysiological manifestation of underlying electromagnetic processes triggered by ionic currents across neuronal membranes. Rather than being the fundamental neural signal itself, the action potential may represent a measurable membrane-level response associated with the successful activation of these electromagnetic events. Moreover, we discuss a possible mechanism for long-term memory storage. Considering the apparent temporal contradiction between the millisecond-scale excitation of neurons and the long-term persistence of memories, we believe that long-term memory information may be stored within neural network topologies formed by electrical synapse coupling. Such structures, referred to as electrically coupled memory networks (ECMNs), may enable neurons within the same network to respond rapidly and synchronously to stimuli, thereby facilitating efficient memory retrieval. Overall, this study emphasizes the importance of considering the temporal organization of neural electromagnetic activities when interpreting neural signaling mechanisms. It may provide new insights into the physical nature of neural information carriers and the mechanisms of memory storage and retrieval. Furthermore, highlighting the potential role of electromagnetic interactions in neural activity may contribute to the development of new theoretical frameworks and experimental approaches in neuroscience. Such perspectives may also offer valuable references for future research on neural coding, brain function mechanisms, and neuromodulation technologies.

ObjectiveThis study employs a special conformational engineering (CE) technology to construct an α-chymotrypsin-like active center, which includes a catalytic triad, an oxyanion hole, and a substrate-binding site, on silver nanoparticles (AgNPs), thereby creating an AgNP-based artificial hydrolase with high catalytic activity. This study provides a new approach for the design of highly efficient artificial enzymes and enzyme-mimicking. MethodsAgNPs were chosen as the scaffold to build the an α-chymotrypsin-like active center. A special CE procedure enables the designed peptide, Triad5, to adopt an α‑helical conformation on AgNPs, with the key catalytic residues located on one side of the α-helix forming a catalytic active center with a catalytic triad, an oxyanion hole, and a substrate-binding site. The CE procedure consists of three steps, including conformation induction via trifluoroethanol (TFE), conformation stabilization on AgNPs via Ag-S bonds, and TFE removal via lyophilization. Circular dichroism (CD) spectra were used to confirm the formation and stabilization of the α-helix conformation. Mutations of the key residues combined with stopped-flow kinetic experiments were used to demonstrate the indispensability of each key residue and the synergistic effects among the catalytic triad, the oxyanion hole, and the substrate-binding site. ResultsCD spectra show that the designed Triad5 alone is in random coil conformation; when conjugated on AgNPs, Triad5 still remains largely unstructured; but after the CE treatment, Triad5 adopts a typical α-helical conformation on AgNPs as designed, thus produces an AgNP-based artificial hydrolase, Silverzyme. Silverzyme exhibits extremely high hydrolytic activity towards p-nitrophenyl acetate (p-NPA), with an extremely high catalytic turnover number per active site of 3.5 s^-1, which is even higher than that of α-chymotrypsin. As a comparison, the AgNP-Triad5 conjugate without CE treatment shows much lower catalytic activity than Silverzyme, highlighting the important role of the right conformation of the active center for the catalytic activity and the power of the CE treatment. When the key residues of the catalytic triad of Silverzyme were mutated to alanine, the overall catalytic efficiency of this mutant dropped by about 2 orders of magnitude, unambiguously demonstrating the key role of the designed catalytic triad. Similarly, when the residues for the oxyanion hole were deleted, the mutant with the intact catalytic triad also showed significantly decreased catalytic activity, highlighting the indispensable role of the oxyanion hole for the catalytic activity. Unexpectedly, when both the catalytic triad and the oxyanion hole were kept intact, a slight change of the binding site also resulted in significantly decreased catalytic activity, indicating that the designed binding site is at the right position to align the substrate in the right orientation in the active center for catalytic hydrolysis. These results confirm the synergy among the catalytic triad, the oxyanion hole, and the substrate-binding site, indicating successful mimicking of the active center of α-chymotrypsin. Moreover, Silverzyme shows better thermal stability than α-chymotrypsin, and can even hydrolyze the tough non-activated ester diethyl phthalate, a priority pollutant by the United States Environmental Protection Agency (USEPA). ConclusionThis study successfully mimicked the complex catalytic active center of α-chymotrypsin using a conformational engineering strategy, and produced a highly active artificial hydrolase with a well-defined structure and catalytic mechanism. The findings highlight the significant potential of conformational engineering.

Objective To explore the echocardiographic features of critically ill patients with infection, and to evaluate the predictive value of echocardiographic parameters for 28-day mortality and myocardial injury. Methods Using a single-center prospective cohort design, 120 critically ill patients with infection admitted to the Intensive Care Unit, Jinshan Hospital of Fudan University from January 2024 to January 2025 were enrolled consecutively. According to the severity of infection, patients were divided into the sepsis group (n＝75) and the non-sepsis group (n＝45). Cox proportional hazards models and modified Poisson regression were used to analyze risk factors of 28-day all-cause mortality and myocardial injury. Kaplan-Meier survival curve and log-rank test were used to assess prognosis differences among patients with different ultrasound parameters. ROC curve and area under the curve (AUC) were applied to evaluate the predictive performance of ultrasound parameters, and restricted cubic spline (RCS) model was used to explore nonlinear relationships. Results The E/e′ ratio was significantly higher in the sepsis group than in the non-sepsis group (P＜0.001), while left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were lower in the sepsis group (P＜0.05). The Cox proportional hazards model found no association between ultrasound parameters and 28-day all-cause mortality. Modified Poisson regression showed that, after adjusting for confounding factors, elevated E/e′ was an independent risk factor of myocardial injury (RR＝1.12, 95% CI 1.07–1.17, P＜0.001). Survival analysis demonstrated that patients with E/e′ ＞10.9 had lower 28-day survival rates (P＝0.02), and the AUC for E/e′ predicting myocardial injury was 0.835. RCS analysis suggested a nonlinear relationship between E/e′ and myocardial injury risk (P＜0.001). Conclusions E/e′, LVEF, and LVFS have no significant predictive value for 28-day mortality risk in critically ill patients with infections. Elevated E/e′ is an independent risk factor of myocardial injury in such patients, with a nonlinear relationship.