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This viewpoint article first explores the ethical challenges associated with the future application of large language models (LLMs) in the context of medical education. These challenges include not only ethical concerns related to the development of LLMs, such as artificial intelligence (AI) hallucinations, information bias, privacy and data risks, and deficiencies in terms of transparency and interpretability but also issues concerning the application of LLMs, including deficiencies in emotional intelligence, educational inequities, problems with academic integrity, and questions of responsibility and copyright ownership. This paper then analyzes existing AI-related legal and ethical frameworks and highlights their limitations with regard to the application of LLMs in the context of medical education. To ensure that LLMs are integrated in a responsible and safe manner, the authors recommend the development of a unified ethical framework that is specifically tailored for LLMs in this field. This framework should be based on 8 fundamental principles: quality control and supervision mechanisms; privacy and data protection; transparency and interpretability; fairness and equal treatment; academic integrity and moral norms; accountability and traceability; protection and respect for intellectual property; and the promotion of educational research and innovation. The authors further discuss specific measures that can be taken to implement these principles, thereby laying a solid foundation for the development of a comprehensive and actionable ethical framework. Such a unified ethical framework based on these 8 fundamental principles can provide clear guidance and support for the application of LLMs in the context of medical education. This approach can help establish a balance between technological advancement and ethical safeguards, thereby ensuring that medical education can progress without compromising the principles of fairness, justice, or patient safety and establishing a more equitable, safer, and more efficient environment for medical education.

Background: The modification of N6‐methyladenosine (m6A) plays a pivotal role in tumor by altering both innate and adaptive immune systems through various pathways, including the regulation of messenger RNA. The YTH domain protein family, acting as "readers" of m6A modifications, affects RNA splicing, stability, and immunogenicity, thereby playing essential roles in immune regulation and antitumor immunity. Despite their significance, the impact of the YTH domain protein family on tumor initiation and progression, as well as their involvement in tumor immune regulation and therapy, remains underexplored and lacks comprehensive review. Conclusion: This review introduces the molecular characteristics of the YTH domain protein family and their physiological and pathological roles in biological behavior, emphasizing their mechanisms in regulating immune responses and antitumor immunity. Additionally, the review discusses the roles of the YTH domain protein family in immune‐related diseases and tumor resistance, highlighting that abnormal expression or dysfunction of YTH proteins is closely linked to tumor resistance. Key points: This review provides an in‐depth understanding of the YTH domain protein family in immune regulation and antitumor immunity, suggesting new strategies and directions for immunotherapy of related diseases.These insights not only deepen our comprehension of m6A modifications and YTH protein functions but also pave the way for future research and clinical applications. [ABSTRACT FROM AUTHOR]

As an essential intracellular immune activation pathway, the cGAS‐STING pathway has attracted broad attention in cancer treatment. However, low bioavailability, nonspecificity, and adverse effects of small molecule STING agonists severely limit their therapeutic efficacy and in vivo application. In this study, a peptide‐based STING agonist is first proposed, and KLA is screened out to activate the cGAS‐STING pathway by promoting mitochondrial DNA (mtDNA) leakage. To precisely activate the cGAS‐STING pathway and block the PD‐1/PD‐L1 pathway, a multi‐stimuli activatable peptide nanodrug (MAPN) is developed for the effective delivery of KLA and PD‐L1 antagonist peptide (CVR). With rational design, MAPN achieved the site‐specific release of KLA and CVR in response to multiple endogenous stimuli, simultaneously activating the cGAS‐STING pathway and blocking PD‐1/PD‐L1 pathway, ultimately initiating robust and durable T cell anti‐tumor immunity with a tumor growth inhibition rate of 78% and extending the median survival time of B16F10 tumor‐bearing mice to 40 days. Overall, antimicrobial peptides, which can promote mtDNA leakage through damaging mitochondrial membranes, may be potential alternatives for small molecule STING agonists and giving a new insight for the design of novel STING agonists. Furthermore, MAPN presents a universal delivery platform for the effective synergy of multiple peptides. [ABSTRACT FROM AUTHOR]

The concept of production stability in hot strip rolling encapsulates the ability of a production line to consistently maintain its output levels and uphold the quality of its products, thus embodying the steady and uninterrupted nature of the production yield. This scholarly paper focuses on the paramount looper equipment in the finishing rolling area, utilizing it as a case study to investigate approaches for identifying the origins of instabilities, specifically when faced with inadequate looper performance. Initially, the paper establishes the equipment process accuracy evaluation (EPAE) model for the looper, grounded in the precision of the looper's operational process, to accurately depict the looper's functioning state. Subsequently, it delves into the interplay between the EPAE metrics and overall production stability, advocating for the use of EPAE scores as direct indicators of production stability. The study further introduces a novel algorithm designed to trace the root causes of issues, categorizing them into material, equipment, and control factors, thereby facilitating on-site fault rectification. Finally, the practicality and effectiveness of this methodology are substantiated through its application on the 2250 hot rolling equipment production line. This paper provides a new approach for fault tracing in the hot rolling process. [ABSTRACT FROM AUTHOR]

The evaluation of limb status with the Wound, Ischaemia, and foot Infection (WIfI) classification and the assessment of patient risks combined with systemic factors, are recommended in patients with chronic limb threatening ischaemia (CLTI). However, there is little evidence of the application of the WIfI classification in the Chinese population. This study aimed to verify the use of the WIfI classification in a Chinese patient population, and to further identify local and systemic independent predictors of adverse CLTI outcomes. A total of 474 patients who underwent endovascular therapy (EVT) for CLTI in a tertiary hospital between July 2017 and September 2020 were included in this retrospective study. The outcomes included one year major adverse limb events (MALEs), one year all cause mortality, and one year amputation free survival (AFS). Cox regression was used to analyse the association between risk factors and adverse outcomes. In total, 104 (21.9%) all cause deaths were recorded. The rate of MALEs was 17.5%, while the AFS was 71.9%. Multivariable analysis revealed that a body mass index (BMI) < 18.5 kg/m2 (p =.002), a left ventricular ejection fraction (LVEF) < 50% (p <.001), and WIfI wound grade (p <.001) were independent risk factors for MALEs, while age ≥ 77 years (p =.031), BMI < 18.5 kg/m2 (p <.001), coronary heart disease (p =.040), and WIfI clinical stages (p =.021) were independent risk factors for death in patients with CLTI. Age ≥ 77 years (p =.003), BMI < 18.5 kg/m2 (p <.001), coronary heart disease (p =.012), LVEF < 50% (p <.001), WIfI wound grade (p =.004), and WIfI clinical stages (p =.044) were independently associated with a decreased AFS rate. This study has confirmed the predictive ability of the WIfI classification for Chinese patients with CLTI who underwent EVT. Wound grade was the most sensitive and important risk factor of the three components of WIfI. In addition, systemic factors should be considered to ensure a more accurate prognosis prediction and appropriate clinical decision making in patients with CLTI. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the safety and efficacy of pharmacomechanical catheter-directed thrombolysis (PCDT) and stenting for treating acute iliofemoral deep venous thrombosis (DVT) combined with iliac vein compression syndrome (IVCS), and to identify the predictors of stent restenosis. Patients with acute proximal DVT combined with IVCS underwent PCDT and stenting from January 2017 to December 2022 were enrolled. Primary and secondary patency were assessed by duplex ultrasound (DUS). The morbidity of postthrombotic syndrome (PTS) was assessed by the Villalta score. Risk factors for stent restenosis were assessed using univariate and multivariate Cox regression models. Total of 254 patients were included. The mean follow-up time was 36.06 ± 17.66 months. The primary patency rates at 1 year, 3 years, and 5 years were 92.5%±1.7%, 85.4%±2.4%, and 82.4%±2.9%, respectively. The incidence of stent restenosis was 14.2%. Discontinuation of anticoagulants within one year [hazard ratio (HR) = 5.03; P  = .048] was the factor associated with acute in-stent thrombosis. Previous DVT history (HR =2.29; P = .037) and stent placement across the inguinal ligament (HR =6.70; P  < .001) were identified as independent risk factors significantly associated with stent restenosis. The overall PTS rate was 19.3%. PCDT with stenting is safe and effective for patients with iliofemoral DVT secondary to IVCS, leading to low rates of PTS. Previous DVT history and stents placed across the inguinal ligament may be predictors of stent restenosis. Furthermore, stent restenosis typically occurs within one year and is mainly caused by acute thrombosis due to discontinuation of anticoagulants., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background and Aims: Percutaneous mechanical thrombectomy (PMT) along with postoperative thrombolysis (POT) has been the standard treatment for acute iliofemoral deep venous thrombosis (IFDVT). However, commonly used catheter directed thrombolysis (CDT) approaches for POT carry certain disadvantages, including the need for a sheath, inferior comfortability, and catheter-related complications. Therefore, we propose a new simplified method of POT using a central venous catheter (CVC)., Methods: The retrospective study analyzed patients with IFDVT who underwent POT using CVC from January 2020 to August 2021. The treatment modalities included filter placement, thrombus removal, iliac vein obstruction release, postoperative CVC thrombolysis, filter retrieval, and adequate full course anticoagulation., Results: A total of 39 patients were included in this retrospective study. All patients underwent PMT surgery with a procedure success rate of 100%. In the post-PMT CVC thrombolysis, the puncture sites were located in the below-knee vein, including 58.97% in the peroneal vein. The mean duration of CVC-directed thrombolysis was 3.69 ± 1.08 days, and the total urokinase dose was 2.27 ± 0.71 MIU. A total of 37 patients (94.87%) had successful thrombolysis with a length of hospital stay of 5.82 ± 2.21 days. During CVC-directed thrombolysis, only four minor bleeding complications occurred, two of which were indwelling catheter-related. During the 12-month follow-up period, the patency rate and post-thrombotic syndrome incidences were 97.44% and 2.56%, respectively., Conclusion: Thrombolysis through a CVC is a feasible, safe, and effective POT method, and could be an alternative to the conventional CDT approach for patients with IFDVT.

Background: Arterial restenosis after percutaneous transluminal angioplasty (PTA) significantly reduces its therapeutic efficacy in treating lower extremity atherosclerotic occlusive diseases (LEAOD). Early external X-ray external radiation has demonstrated positive effects on restenosis; however, effective dosing and the mechanism(s) underlying its efficacy remain unknown. This study explored the effect of early external X-ray radiation on preventing post-PTA restenosis in an iliac intimal injury model., Methods: Twenty rabbits underwent iliac intimal injury via PTA and received five different radiation doses: 0 Gy (n=4), 3 Gy (n=4), 6 Gy (n=4), 9 Gy (n=4), and 12 Gy (n=4). Four rabbits were used as controls. All subjects were fed a high-fat diet prior to PTA and for an additional four-week period post-PTA and then sacrificed for immunohistochemical and Western blotting analysis., Results: Arterial stenosis was significantly improved post-PTA. Alpha smooth muscle actin (α-SMA) expression in the 0 Gy to 9 Gy groups was significantly increased post-PTA. Cytochrome C (Cyt C) expression was significantly increased post-PTA and was positively correlated with radiation intensity. Proliferating cell nuclear antigen (PCNA) expression was significantly increased post-PTA with the 0 Gy group showing significantly higher expression than the 3 Gy group. No significant differences were found in CD34 levels between the groups., Conclusions: Early external X-ray radiation at 6-24 Gy doses effectively restrained VSMC hyperplasia post-PTA, likely through inducing VSMC apoptosis via mitochondrial Cyt C release. However, this technique did not significantly affect the integrity of the vascular endothelium. Therefore, early external X-ray radiation shows promise in preventing post-PTA restenosis.

Background: Arterial restenosis after percutaneous transluminal angioplasty (PTA) significantly reduces its therapeutic efficacy in treating lower extremity atherosclerotic occlusive diseases (LEAOD). Early external X-ray external radiation has demonstrated positive effects on restenosis; however, effective dosing and the mechanism(s) underlying its efficacy remain unknown. This study explored the effect of early external X-ray radiation on preventing post-PTA restenosis in an iliac intimal injury model., Methods: Twenty rabbits underwent iliac intimal injury via PTA and received five different radiation doses: 0 Gy (n = 4), 3 Gy (n = 4), 6 Gy (n = 4), 9 Gy (n = 4), and 12 Gy (n = 4). Four rabbits were used as controls. All subjects were fed a high-fat diet prior to PTA and for an additional four-week period post-PTA and then sacrificed for immunohistochemical and Western blotting analysis., Results: Arterial stenosis was significantly improved post-PTA. Alpha smooth muscle actin (α-SMA) expression in the 0 Gy to 9 Gy groups was significantly increased post-PTA. Cytochrome C (Cyt C) expression was significantly increased post-PTA and was positively correlated with radiation intensity. Proliferating cell nuclear antigen (PCNA) expression was significantly increased post-PTA with the 0 Gy group showing significantly higher expression than the 3 Gy group. No significant differences were found in CD34 levels between the groups., Conclusions: Early external X-ray radiation at 6-24 Gy doses effectively restrained VSMC hyperplasia post-PTA, likely through inducing VSMC apoptosis via mitochondrial Cyt C release. However, this technique did not significantly affect the integrity of the vascular endothelium. Therefore, early external X-ray radiation shows promise in preventing post-PTA restenosis.

Objective: Proliferation of vascular smooth muscle cells (VSMCs) is a crucial event in the pathogenesis of intimal hyperplasia, the main cause of restenosis following vascular reconstruction. Here, the impact of sonic hedgehog (Shh)/Gli family zinc finger 2 (Gli2) signaling on VSMC proliferation was assessed., Methods and Results: Increased Shh signaling was detected in VSMCs in the neointima of vein grafts obtained from mice undergoing restenosis. Comparable results were found in primary cultured human VSMCs (hVSMCs) obtained from patients undergoing coronary bypass surgery, which were used to further assess the impacts of Shh signaling on VSMC proliferation. Inhibition of Shh signaling in hVSMCs through treatment with cyclopamine or knockdown of Gli2 results in G(1) arrest and reduced cyclin D1, cyclin E, and phosphorylated retinoblastoma (pRB) levels. In contrast, activation of Shh/Gli2 signaling in hVSMCs results in increased levels of G(1) cyclins and promotes G(1)-S transition. Stimulation of hVSMC proliferation by Shh is abolished by cyclin D1 knockdown., Conclusions: Combined, these results demonstrate that Shh/Gli2 signaling stimulates VSMC proliferation via regulation of the G(1) cyclin-retinoblastoma axis and suggest that antagonists that target the Shh pathway may be therapeutically beneficial in the prevention of intimal hyperplasia.