Objective To observe the effects of Yixintai on lipid metabolism and the protein expressions of CPT-1 and CD36 in rats with heart failure;To explore the mechanism of its treatment of heart failure.Methods 106 out of 120 SD rats were selected to establish the heart failure model induced by myocardial infarction by ligating the left anterior descending coronary artery,and 14 rats were selected as the sham-operation group.The successful model rats were randomly divided into model group,trimetazidine group and Yixintai low-,medium-and high-dosage groups,with 14 rats in each group.The administration group was given corresponding drugs by gavage once a day for 4 weeks.LVEF,LVFS,LVIDd and LVIDs were measured by color doppler ultrasonography,the contents of ANP,BNP,LA and FFA in serum were detected by ELISA,the contents of TG,TC,LDL and HDL were detected by automatic biochemical analyzer,HE and Masson staining were used to observe the morphology of myocardial tissue,the expressions of CPT-1 and CD36 protein in myocardial tissue were detected by Western blot.Results Compared with the sham-operation group,LVEF and LVFS in the model group decreased(P<0.05),the LVIDs and LVIDd increased(P<0.05);the contents of serum ANP,BNP,LA,FFA,TG,TC and LDL increased(P<0.05),while the content of HDL decreased(P<0.05),with myocardial edema,irregular arrangement of myocardial fibers,increased inflammatory cell infiltration and collagen fiber deposition;the protein expressions of CPT-1 and CD36 in myocardial tissue decreased(P<0.05).Compared with the model group,the LVEF and LVFS in Yixintai each dosage groups and trimetazidine group increased(P<0.05),LVIDs and LVIDd decreased(P<0.05);the contents of ANP,BNP,LA,FFA,TG,TC and LDL in serum of Yixintai medium-and high-dosage groups and trimetazidine group decreased(P<0.05),the content of HDL increased(P<0.05);myocardial edema was improved,inflammatory cell infiltration was reduced,collagen fiber deposition was reduced,and the protein expressions of CPT-1 and CD36 in myocardial tissue increased(P<0.05).Conclusion Yixintai may improve myocardial energy metabolism and treat heart failure by increasing the expression of CPT-1 and CD36 protein in myocardial tissue and promoting fatty acid β oxidation.

Objective:To develop a novel fibroblast activation protein (FAP) cyclic peptide imaging agent, Al 18F-FAP-NOX, evaluate its in vitro and in vivo properties, and explore its feasibility of PET/CT imaging in tumors with FAP positive expression. Methods:Al 18F-FAP-NOX was manually synthesized. The in vitro stability of Al 18F-FAP-NOX was determined using radio high performance liquid chromatography (HPLC). The lipid water partition coefficient log P, in vitro cell uptake experiments, microPET/CT imaging and biodistribution in 293T-FAP tumor-bearing mice were conducted to preliminarily evaluate the pharmacokinetics and biological efficacy of Al 18F-FAP-NOX. Afterwards, a patient (male, 65 years old) with lung cancer underwent Al 18F-FAP-NOX PET/CT imaging. Results:Al 18F-FAP-NOX was successfully synthesized with a yield of (26.28±2.31)% without attenuation correction ( n=4), and the radiochemical purity was more than 95%. Al 18F-FAP-NOX exhibited good stability and hydrophilicity (log P=-3.02±0.08, n=5). In cell assays, the uptake of Al 18F-FAP-NOX in HT1080-FAP cells reached the plateau phase at 15 min ((7.31±0.53) percentage activity of injection dose per million cells (%ID/mio cells)), exhibiting high cellular uptake. The uptake of Al 18F-FAP-NOX could be significantly inhibited by 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)-FAP-2286. The microPET/CT results of 293T-FAP tumor-bearing mice in vivo showed that Al 18F-FAP-NOX was highly uptaken in FAP-positive tumor tissues (60 min: (12.47±1.66) percentage activity of injection dose per gram of tissue (%ID/g)), while the uptake was very low in FAP-negative tumors. The biodistribution results were similar to the microPET/CT imaging results of tumor-bearing mice. The human clinical imaging showed an abnormal increase in Al 18F-FAP-NOX uptake (SUV max 5.5) of the lung cancer lesions. Conclusions:A novel cyclic peptide radiopharmaceutical, Al 18F-FAP-NOX, demonstrates good stability and hydrophilicity. It can be quickly distributed to tumor tissue in vivo. The human clinical PET/CT imaging shows certain diagnostic ability of Al 18F-FAP-NOX for lung cancer lesions. It is a promising cyclic peptide agent for PET imaging.

Objective:To systematically evaluate the safety and efficacy of the novel fibroblast activation protein (FAP)-targeted tracer 64Cu-FAP inhibitor (FAPI)-XT117 in patients with malignant solid tumors, and to compare with 18F-FDG. Methods:This self-controlled study was conducted on fifteen patients (8 males, 7 females; age (60 ±9) years) with malignant solid tumors from the First Affiliated Hospital of Guangzhou Medical University between July 2023 and December 2023. Each subject underwent 64Cu-FAPI-XT117 PET/CT at 30, 60, and 120min post-injection and was assigned to three dose cohorts (111MBq, 148MBq, and 185MBq; 5 patients in each cohort), and safety assessments were conducted within 24h after injection. In addition, all patients underwent 18F-FDG PET/CT at 60min post-injection. Time-activity curves were generated for 64Cu-FAPI-XT117, and the dosimetry was calculated. Image quality was evaluated using a 5-point Likert scale, and the optimal injected activity and imaging time point were determined. The paired t test was used to compare differences of the lesion detection count and SUV max between 64Cu-FAPI-XT117 and 18F-FDG PET/CT. Results:64Cu-FAPI-XT117 was well tolerated, with no adverse events reported. Time-activity curves of 68Ga-FAPI-XT117 revealed prominent uptake in the uterus, while the background activity in other organs remained low, with the whole-body effective dose of (0.0084±0.0021)mSv/MBq. The optimal imaging time point for 64Cu-FAPI-XT117 PET/CT was 60min post-injection, with an optimal administered activity of 111MBq. Compared with 18F-FDG, 64Cu-FAPI-XT117 demonstrated significantly higher uptake and more lesions in lymph-node metastases (SUV max: 8.6±3.8 vs 15.3±6.8, t=2.33, P=0.048; number of lesions: 8.3±5.4 vs 15.0±6.4; t=4.21, P=0.003) and distant metastases (SUV max: 11.8±3.7 vs 20.9±7.2, t=3.66, P=0.022; number of lesions: 7.0±3.2 vs 12.4±3.7, t=2.86, P=0.046). Conclusions:64Cu-FAPI-XT117 PET/CT is well tolerated in patients with solid tumors, with a controllable radiation risk. Moreover, it outperforms 18F-FDG PET/CT in the assessment of metastases.

OBJECTIVE To study the effects of Ro 64-6198,a selective nociceptin/orphanin FQ receptor(NOPR)agonist,on heroin self-administration and drug-seeking behavior in rats.METHODS Rats were trained to self-administer heroin intravenously at a dose of 0.05 mg·kg-1 under a fixed ratio 1(FR1)reinforcement schedule.Heroin motivation was assessed using a progressive ratio(PR)schedule.Firstly,a stable heroin self-administered rat model was established before the effects of Ro 64-6198 on heroin rewarding under the FR1 schedule were observed.After three days of self-administration recovery training,the effects of Ro 64-6198 on heroin reward motivation were observed under the PR3-4 schedule.Following extinction,the reinstatement of heroin seeking induced by either conditioned cues or heroin priming was evaluated in rats withdrawn from self-administration.The expressions of cAMP response element-binding protein(CREB)and brain-derived neurotrophic factor(BDNF)in the ventral tegmental area(VTA)were analyzed using Western blotting,while the expression of the NOPR in neurons in the VTA was examined through immunofluorescence staining.RESULTS Pretreatment with 3 mg·kg-1 Ro 64-6198 significantly reduced active responses and heroin infusions during FR1 testing,as well as decreased breakpoints,indicating reduced motivation under the PR schedule.At a dose of 1 mg·kg-1,Ro 64-6198 markedly attenuated the reinstatement of heroin-seeking behavior induced by conditioned cues or heroin priming.Furthermore,the administration of SB-612111,an NOPR antagonist,blocked the inhibitory effects of Ro 64-6198 on cue-induced heroin-seeking,although SB-612111 alone had no effect on heroin-seeking behavior.Ro 64-6198 treatment also suppressed the reduction of both phos-phorylated CREB(p-CREB)and BDNF levels in the VTA and the decreased expression of NOPR and p-CREB in dopaminergic neurons of the VTA.CONCLUSION These results demonstrate that Ro 64-6198 can mitigate heroin-seeking behavior through NOPR activation and CREB/BDNF pathway in the VTA.This study is expected to offer evidence for its potential as a clinical treatment for heroin addiction and relapse.

This comprehensive review systematically explores the multifaceted applications, inherent challenges, and promising future directions of artificial intelligence (AI) within the medical domain. It meticulously examines AI's specific contributions to basic medical research, disease prevention, intelligent diagnosis, treatment, rehabilitation, nursing, and health management. Furthermore, the review delves into AI's innovative practices and pivotal roles in clinical trials, hospital administration, medical education, as well as the realms of medical ethics and policy formulation. Notably, the review identifies several key challenges confronting AI in healthcare, encompassing issues such as inadequate algorithm transparency, data privacy concerns, absent regulatory standards, and incomplete risk assessment frameworks. Looking ahead, the future trajectory of AI in healthcare encompasses enhancing algorithm interpretability, propelling generative AI applications, establishing robust data-sharing mechanisms, refining regulatory policies and standards, nurturing interdisciplinary talent, fostering collaboration among industry, academia, and medical institutions, and advancing inclusive, personalized precision medicine. Emphasizing the synergy between AI and emerging technologies like 5G, big data, and cloud computing, this review anticipates a new era of intelligent collaboration and inclusive sharing in healthcare. Through a multidimensional analysis, it presents a holistic overview of AI's medical applications and development prospects, catering to researchers, practitioners, and policymakers in the healthcare sector. Ultimately, this review aims to catalyze the deep integration and innovative deployment of AI technology in healthcare, thereby driving the sustainable advancement of smart healthcare.

As the volume of medical research using large language models (LLM) surges, the need for standardized and transparent reporting standards becomes increasingly critical. In January 2025, Nature Medicine published statement titled by TRIPOD-LLM reporting guideline for studies using large language models. This represents the first comprehensive reporting framework specifically tailored for studies that develop prediction models based on LLM. It comprises a checklist with 19 main items (encompassing 50 sub-items), a flowchart, and an abstract checklist (containing 12 items). This article provides an interpretation of TRIPOD-LLM’s development methods, primary content, scope, and the specific details of its items. The goal is to help researchers, clinicians, editors, and healthcare decision-makers to deeply understand and correctly apply TRIPOD-LLM, thereby improving the quality and transparency of LLM medical research reporting and promoting the standardized and ethical integration of LLM into healthcare.

Objective:To explore the chain mediating effect of empowerment and activation between chronic disease resources and self-management in elderly patients with chronic obstructive pulmonary disease (COPD) .Methods:A convenience sampling method was used to select 306 elderly COPD patients who were treated at the Affiliated Hospital of Shaoxing University from December 2022 to May 2024. General information questionnaires, COPD Self-Management Scale (COPD-SMS), Chronic Illness Resources Survey-Chinese version (CIRS-C), COPD Empowerment Evaluation Scale, and the Patient Activation Measure (PAM 13) were used for the survey. AMOS 22.0 software was employed to construct a structural equation model to analyze the pathways influencing self-management in COPD patients.Results:A total of 306 questionnaires were distributed, with 291 valid ones returned, resulting in an effective response rate of 95.10%. Empowerment and activation played a mediating role between chronic disease resources and self-management in elderly COPD patients. A total of three pathways were identified: chronic disease resources→activation→self-management (effect size=0.099, accounting for 18.07% of the total effect), chronic disease resources→empowerment→self-management (effect size=0.084, accounting for 15.33% of the total effect), and chronic disease resources→empowerment →activation→self-management (effect size=0.039, accounting for 7.11% of the total effect). Chronic disease resources also had a direct effect on self-management (effect size=0.326, accounting for 59.49% of the total effect) .Conclusions:The self-management level of elderly COPD patients urgently needs improvement. Nursing staff should focus on optimizing the allocation of chronic disease resources for elderly COPD patients, empowering them to stimulate activation and promote the improvement of their self-management abilities.

In observational research,a primary objective is to accurately and reliably assess the causal impact of exposure on outcomes.Identifying and properly adjusting for confounding factors is a key prerequisite and central challenge to achieving this goal.Ineffective management of confounders,whether by neglecting significant ones,(leading to residual confounding),or by over-adjusting for irrelevant factors,(introducing collider bias),can distort effect estimates and lead to erroneous scientific conclusions and clinical decisions.Therefore,it is essential to develop and implement systematic,transparent,and reproducible methods for identifying and selecting confounding factors to enhance the validity and reliability of causal inferences in observational studies.This paper provides a systematic review of directed acyclic graphs(DAGs),a robust visual causal modeling tool,and offers a detailed examination of three prominent criteria for selecting confounding factors based on DAGs:the Pre-exposure criterion,the Common cause criterion,and the Modified disjunctive cause criterion.The aim is to equip researchers with a structured and theoretically grounded framework for identifying and selecting confounding factors,thereby improving the process of estimating causal effects in observational studies.

In observational research,a primary objective is to accurately and reliably assess the causal impact of exposure on outcomes.Identifying and properly adjusting for confounding factors is a key prerequisite and central challenge to achieving this goal.Ineffective management of confounders,whether by neglecting significant ones,(leading to residual confounding),or by over-adjusting for irrelevant factors,(introducing collider bias),can distort effect estimates and lead to erroneous scientific conclusions and clinical decisions.Therefore,it is essential to develop and implement systematic,transparent,and reproducible methods for identifying and selecting confounding factors to enhance the validity and reliability of causal inferences in observational studies.This paper provides a systematic review of directed acyclic graphs(DAGs),a robust visual causal modeling tool,and offers a detailed examination of three prominent criteria for selecting confounding factors based on DAGs:the Pre-exposure criterion,the Common cause criterion,and the Modified disjunctive cause criterion.The aim is to equip researchers with a structured and theoretically grounded framework for identifying and selecting confounding factors,thereby improving the process of estimating causal effects in observational studies.

OBJECTIVE To study the effects of Ro 64-6198,a selective nociceptin/orphanin FQ receptor(NOPR)agonist,on heroin self-administration and drug-seeking behavior in rats.METHODS Rats were trained to self-administer heroin intravenously at a dose of 0.05 mg·kg-1 under a fixed ratio 1(FR1)reinforcement schedule.Heroin motivation was assessed using a progressive ratio(PR)schedule.Firstly,a stable heroin self-administered rat model was established before the effects of Ro 64-6198 on heroin rewarding under the FR1 schedule were observed.After three days of self-administration recovery training,the effects of Ro 64-6198 on heroin reward motivation were observed under the PR3-4 schedule.Following extinction,the reinstatement of heroin seeking induced by either conditioned cues or heroin priming was evaluated in rats withdrawn from self-administration.The expressions of cAMP response element-binding protein(CREB)and brain-derived neurotrophic factor(BDNF)in the ventral tegmental area(VTA)were analyzed using Western blotting,while the expression of the NOPR in neurons in the VTA was examined through immunofluorescence staining.RESULTS Pretreatment with 3 mg·kg-1 Ro 64-6198 significantly reduced active responses and heroin infusions during FR1 testing,as well as decreased breakpoints,indicating reduced motivation under the PR schedule.At a dose of 1 mg·kg-1,Ro 64-6198 markedly attenuated the reinstatement of heroin-seeking behavior induced by conditioned cues or heroin priming.Furthermore,the administration of SB-612111,an NOPR antagonist,blocked the inhibitory effects of Ro 64-6198 on cue-induced heroin-seeking,although SB-612111 alone had no effect on heroin-seeking behavior.Ro 64-6198 treatment also suppressed the reduction of both phos-phorylated CREB(p-CREB)and BDNF levels in the VTA and the decreased expression of NOPR and p-CREB in dopaminergic neurons of the VTA.CONCLUSION These results demonstrate that Ro 64-6198 can mitigate heroin-seeking behavior through NOPR activation and CREB/BDNF pathway in the VTA.This study is expected to offer evidence for its potential as a clinical treatment for heroin addiction and relapse.