Chronic heart failure （CHF） is a group of complex clinical syndromes caused by abnormal changes in the structure and/or function of the heart due to various reasons， resulting in disorders of ventricular contraction and/or diastole. CHF is a condition where primary diseases such as coronary heart disease， hypertension and pulmonary heart disease recur frequently and persist for a long time， presenting blood stasis in meridians and collaterals， stagnation of water and dampness， and accumulation of Qi in collaterals. Its pathogenesis is complex and may involve myocardial energy metabolism disorders， oxidative stress responses， myocardial cell apoptosis， autophagy， inflammatory responses， etc. According to the theory of restraining hyperactivity to acquire harmony， we believe that under normal circumstances， the adenosine monophosphate-activated protein kinase （AMPK） signaling pathway functions normally， maintaining human physiological activities and energy metabolism. Under pathological conditions， the AMPK signaling pathway is abnormal， causing energy metabolism disorders， inflammatory responses， and myocardial fibrosis. Traditional Chinese medicine （TCM） can regulate the AMPK signaling pathway through multiple mechanisms， targets， and effects， effectively curbing the occurrence and development of CHF. It has gradually become a research hotspot in the prevention and treatment of this disease. Guided by the theory of TCM， our research group， through literature review， summarized the relationship between the AMPK pathway and CHF and reviewed the research progress in the prevention and control of CHF with TCM active ingredients， TCM compound prescriptions， and Chinese patent medicines via regulating the AMPK pathway. The review aims to clarify the mechanism and targets of TCM in the treatment of CHF by regulating the AMPK pathway and guide the clinical treatment and drug development for CHF.

Chronic heart failure （CHF） refers to a clinical syndrome in which the function or structure of the heart is changed due to damage to the original myocardium， resulting in reduced pumping and/or filling functions of the heart. In recent years， the mechanisms， pathways， and targets of traditional Chinese medicine （TCM） in the treatment of CHF have been continuously confirmed， and the application of TCM theories in guiding the syndrome differentiation and precise treatment of CHF is currently a research hotspot. On the basis of the syndrome differentiation and treatment in TCM， Professor LI Candong innovatively proposed the thinking of five differentiation： Disease differentiation， syndrome differentiation， pathogenesis differentiation， symptom differentiation， and individual differentiation. This article explores the clinical diagnosis and treatment of CHF from this thinking， emphasizing comprehensive syndrome differentiation， objective analysis， dynamic assessment， and individualized treatment. In terms of diagnosis， the first is to identify the disease name， cause， location， severity， and type of CHF， determine the type and its evolution， and clarify the process of transmission and transformation between deficiency and excess. Secondly， it is necessary to distinguish the authenticity， severity， primary and secondary， urgency and complexity of CHF syndromes， providing scientific guidance for syndrome differentiation and treatment. Thirdly， according to the symptoms and the principles of deficiency and excess， the physician should identify the core pathogenesis of CHF from the perspectives of Qi， blood， Yin， Yang， deficiency， stasis， phlegm， water， and toxins. Fourthly， from the macro， meso and micro levels， the physician should carefully distinguish the presence or absence， severity， authenticity， and completeness of the symptoms to guide the diagnosis and treatment process of CHF. Finally， personalized medication for CHF should be promoted based on the patient's gender， age， constitution， and living habits. In terms of treatment， based on the thinking of five differentiation， we propose that the treatment of CHF should integrate the disease and syndrome， clarify the pathogenesis， and apply precise treatment. The treatment should be people-oriented， staged， and typed， and the medication should be adjusted according to symptoms. This diagnostic and therapeutic approach is based on the holistic concept and syndrome differentiation and treatment， and combines the three causes for appropriate treatment， providing new ideas and insights for the diagnosis and treatment of CHF.

ObjectiveTo examine the influences of Shenfu injection on the endogenous metabolic byproducts in the myocardium of the rat model exhibiting chronic heart failure， thus deciphering the therapeutic mechanism of the Qi-reinforcing and Yang-warming method. MethodsSD rats were randomly allocated into a control group and a modeling group. Chronic heart failure with heart-Yang deficiency syndrome in rats was modeled by multi-point subcutaneous injection of isoproterenol， and the rats were fed for 14 days after modeling. The successfully modeled rats were randomized into model， Shenfu injection （6.0 mL·kg^-1）， and trimetazidine （10 mg·kg^-1） groups and treated with corresponding agents for 15 days. The control group and the model group were injected with equal doses of normal saline， and the samples were collected after the intervention was completed. Cardiac color ultrasound was performed. Hematoxylin-eosin （HE） staining was used to observe histopathological morphology， and the serum level of N-terminal pro-brain natriuretic peptide （NT-proBNP） was assessed by enzyme-linked immunosorbent assay （ELISA）. The mitochondrial morphological and structural changes of cardiomyocytes were observed by transmission electron microscopy， and the metabolic profiling was carried out by ultra high performance liquid chromatography-quantitative exactive-mass spectrometry （UHPLC-QE-MS）. Differential metabolites were screened and identified by orthogonal partial least squares-discriminant analysis （OPLS-DA） and other methods， and then the MetaboAnalyst database was used for further screening. The relevant biological pathways were obtained through pathway enrichment analysis. The receiver operating characteristic （ROC） curve was established to evaluate the diagnostic value of each potential biomarker for myocardial injury and the evaluation value for drug efficacy. ResultsThe results of color ultrasound showed that Shenfu Injection improved the cardiac function indexes of model rats （P<0.05）. The results of HE staining showed that Shenfu injection effectively alleviated the pathological phenomena such as myocardial tissue structure disorder and inflammatory cell infiltration in model rats. The results of ELISA showed that Shenfu injection effectively regulated the serum NT-proBNP level in the model rats. Transmission electron microscopy （TEM） showed that Shenfu injection effectively restored the mitochondrial morphological structure. The results of metabolomics showed that the metabolic phenotypes of myocardial samples presented markedly differences between groups. Nine differential metabolites could be significantly reversed in the Shenfu injection group， involving three metabolic pathways： pyruvate metabolism， histidine metabolism， and citric acid cycle （TCA cycle）. The results of ROC analysis showed that the area under the curve （AUC） values of all metabolites were between 0.75 and 1.0， indicating that the differential metabolites had high diagnostic accuracy for myocardial injury， and the changes in their expression levels could be used as potential markers for efficacy evaluation. ConclusionShenfu injection significantly alleviated the damage of cardiac function， myocardium， and mitochondrial structure in the rat model of chronic heart failure with heart-Yang deficiency syndrome by ameliorating energy metabolism remodeling. Reinforcing Qi and warming Yang is a key method for treating chronic heart failure with heart-Yang deficiency syndrome.

Objective To develop an artificial intelligence (AI)-driven lung cancer database by structuring and standardizing clinical data, enabling advanced data mining for lung cancer research, and providing high-quality data for real-world studies. Methods Building on the extensive clinical data resources of the Department of Thoracic Surgery at Peking Union Medical College Hospital, this study utilized machine learning techniques, particularly natural language processing (NLP), to automatically process unstructured data from electronic medical records, examination reports, and pathology reports, converting them into structured formats. Data governance and automated cleaning methods were employed to ensure data integrity and consistency. Results As of September 2024, the database included comprehensive data from 18 811 patients, encompassing inpatient and outpatient records, examination and pathology reports, physician orders, and follow-up information, creating a well-structured, multi-dimensional dataset with rich variables. The database’s real-time querying and multi-layer filtering functions enabled researchers to efficiently retrieve study data that meet specific criteria, significantly enhancing data processing speed and advancing research progress. In a real-world application exploring the prognosis of non-small cell lung cancer, the database facilitated the rapid analysis of prognostic factors. Research findings indicated that factors such as tumor staging and comorbidities had a significant impact on patient survival rates, further demonstrating the database’s value in clinical big data mining. Conclusion The AI-driven lung cancer database enhances data management and analysis efficiency, providing strong support for large-scale clinical research, retrospective studies, and disease management. With the ongoing integration of large language models and multi-modal data, the database’s precision and analytical capabilities are expected to improve further, providing stronger support for big data mining and real-world research of lung cancer.

Immobilized enzyme-based enzyme electrode biosensors, characterized by high sensitivity and efficiency, strong specificity, and compact size, demonstrate broad application prospects in life science research, disease diagnosis and monitoring, etc. Immobilization of enzyme is a critical step in determining the performance (stability, sensitivity, and reproducibility) of the biosensors. Random immobilization (physical adsorption, covalent cross-linking, etc.) can easily bring about problems, such as decreased enzyme activity and relatively unstable immobilization. Whereas, directional immobilization utilizing amino acid residue mutation, affinity peptide fusion, or nucleotide-specific binding to restrict the orientation of the enzymes provides new possibilities to solve the problems caused by random immobilization. In this paper, the principles, advantages and disadvantages and the application progress of enzyme electrode biosensors of different directional immobilization strategies for enzyme molecular sensing elements by specific amino acids (lysine, histidine, cysteine, unnatural amino acid) with functional groups introduced based on site-specific mutation, affinity peptides (gold binding peptides, carbon binding peptides, carbohydrate binding domains) fused through genetic engineering, and specific binding between nucleotides and target enzymes (proteins) were reviewed, and the application fields, advantages and limitations of various immobilized enzyme interface characterization techniques were discussed, hoping to provide theoretical and technical guidance for the creation of high-performance enzyme sensing elements and the manufacture of enzyme electrode sensors.

BACKGROUND:Ossification of the ligamentum flavum was previously considered to be rare in the population.As research has progressed,its incidence rate is increasing gradually,which has aroused the interest of a large number of researchers. OBJECTIVE:To visualize and analyze the research results on ossification of the ligamentum flavum from the Web of Science Core Collection since 1999 using bibliometric methods,and to review the research history of ossification of the ligamentum flavum,highlighting important literature,summarizing research hotspots,and providing ideas for researchers to find research directions. METHODS:Using the Web of Science Core Collection as the data source,relevant papers on ossification of the ligamentum flavum were searched and screened.VOSviewer 1.6.19 and CiteSpace 6.2.R6 were used to conduct the visual analysis of annual publication volume,research countries,institutions,citations,journals,authors,and keywords. RESULTS AND CONCLUSION:(1)A total of 347 papers were included.Since 1999,the number of published papers has increased in a spiral pattern.China's research started later than Japan's,but the number of publications has come up later,with Peking University being the institution with the most publications,and Prof.Chen Zhongqiang from Peking University being the scholar with the most publications.(2)Five of the 10 most frequently cited publications were related to the surgical treatment of the disease.(3)Excluding keywords directly related to the research topic and synthetically analyzing frequencies and betweenness centralities of key words,terms such as"thoracic myelopathy,""dural ossification,""minimally invasive surgery,"and"ossification of the posterior longitudinal ligament"occupied a central position in this field.(4)Keywords clustering analysis showed that clinical manifestations and surgical treatment of ossification of the ligamentum flavum accounted for a large proportion of study.(5)The timeline and burst analysis of keywords revealed that"minimally invasive surgery"appeared as a keyword around 2015,with the highest burst strength and the latest burst start time,and began to receive extensive attention from researchers in 2019.The burst of the keyword"dural ossification"has not yet ended.(6)Surgical treatment for ossification of the ligamentum flavum has been at the forefront of research.Development and research of minimally invasive surgery and research on dural ossification secondary to ossification of the ligamentum flavum are both current research hotspots and possible future research trends.

Objective This study aims to investigate the effects of varying durations of light exposure on body weight and learning and memory abilities of pubertal NIH mice. Methods Forty pubertal NIH mice, evenly split by gender and with similar initial weights, were subjected to a 12 h light-dark cycle for one week. They were then randomly assigned to groups with daily light exposure durations of 0, 6, 12, 18, and 24 hours, with 8 mice in each group. The experimental period lasted for 7 weeks, with the first 5 weeks as the feeding phase under different light exposure conditions, and the last 2 weeks as the behavioral testing phase. Their body weight was monitored, and learning and memory abilities were assessed using the T-maze, object location test, and eight-arm maze tests. Results During the light exposure period, there were no significant differences in body weight among groups (P>0.05). However, the weight gain of mice in the 24 h group was significantly higher than that of the 0 h group and the 6 h group during the second and third weeks of light exposure (P<0.05). After five weeks of light exposure, in the T-maze test, the latency time of the 0 h light exposure group was significantly longer than that of the 12 h group (P<0.01), and the latency time of the 24 h light exposure group was significantly longer than that of the 12 h group (P<0.05). In the object location test, the mice in 12 h group exhibited a higher discrimination index and spent more time observing the new location compared to the other groups, with significant differences in comparison to the 18 h group (P<0.01) and the 24 h group (P<0.05). In the eight-arm maze test, the time to find food, the reference memory error rate, and the working memory error rate in the 12 h group were all lower than those in the 0 h group, with significant differences (P<0.05). Moreover, the working memory error rate in the 24 h group was higher than that in the 12 h group, with significant differences (P<0.05). Conclusion Continuous 24 h light exposure affects body weight gain, while light exposure durations exceeding 18 h or below 6 h per day weaken the learning and memory abilities of NIH mice.

Type 1 diabetes mellitus is a chronic autoimmune disease caused by the destruction of pancreatic islet β cells. Pancreatic islet transplantation provides a treatment method for patients with type 1 diabetes mellitus to restore endogenous insulin secretion. However, some problems limit the widespread application of islet transplantation, such as the shortage of donors and post-transplantation rejection damage. Mesenchymal stem cell-derived exosome (MSC-Exo) has become a potential tool for islet transplantation therapy due to their immunomodulatory and tissue repair capabilities. MSC-Exo shows great promise for application, because of low immunogenicity, easily being stored and transported, and the potential as drug delivery vehicles. However, challenges such as preparation, purification, standardization and safety verification need to be overcome before converting MSC-Exo into clinical practice. Therefore, this article reviews the application and potential advantages of MSC-Exo in islet transplantation, aiming to providing more effective and safer treatment options for patients with type 1 diabetes mellitus.

Purpose: Corneal melanoma (CM) is a rare malignancy that develops from melanocytes within the cornea, constituting a minority of all ocular tumors. In this study, we sought to investigate the clinicopathological characteristics correlated with the prognosis of CM patients. Methods: We collected patients with CM between 1983 and 2018 from the Surveillance, Epidemiology, and End Results (SEER) database. Cox proportional hazards regression was used for univariate analysis to value hazard ratio of malignant CM versus spindle cell melanoma and nodular melanoma subgroups. Kaplan-Meier survival analysis and log-rank test were also performed to identify additional prognostic markers and confirm the findings of the Cox hazard ratio. Results: A total of 29 eligible patients were collected in our study. Age at diagnosis, laterality, primary site, tumor size, the extent of disease, marital status, income, residential area, and treatment showed no significant prognostic factors for CM patients (p > 0.05). However, when concerned with the primary site of malignant melanoma, spindle cell melanoma and nodular melanoma were found to show significantly poorer prognosis in CM patients (both p < 0.05). Conclusions Age at diagnosis, laterality, primary site, tumor size, the extent of disease, and treatment were not significant prognostic indicators for CM patients. Spindle cell melanoma and nodular melanoma were notable for showing worse survival outcomes than malignant melanoma. Although the sample size in the SEER database was limited, our findings may provide motivation for tailoring individualized treatments for patients with CM with different primary sites.

Purpose: Corneal melanoma (CM) is a rare malignancy that develops from melanocytes within the cornea, constituting a minority of all ocular tumors. In this study, we sought to investigate the clinicopathological characteristics correlated with the prognosis of CM patients. Methods: We collected patients with CM between 1983 and 2018 from the Surveillance, Epidemiology, and End Results (SEER) database. Cox proportional hazards regression was used for univariate analysis to value hazard ratio of malignant CM versus spindle cell melanoma and nodular melanoma subgroups. Kaplan-Meier survival analysis and log-rank test were also performed to identify additional prognostic markers and confirm the findings of the Cox hazard ratio. Results: A total of 29 eligible patients were collected in our study. Age at diagnosis, laterality, primary site, tumor size, the extent of disease, marital status, income, residential area, and treatment showed no significant prognostic factors for CM patients (p > 0.05). However, when concerned with the primary site of malignant melanoma, spindle cell melanoma and nodular melanoma were found to show significantly poorer prognosis in CM patients (both p < 0.05). Conclusions Age at diagnosis, laterality, primary site, tumor size, the extent of disease, and treatment were not significant prognostic indicators for CM patients. Spindle cell melanoma and nodular melanoma were notable for showing worse survival outcomes than malignant melanoma. Although the sample size in the SEER database was limited, our findings may provide motivation for tailoring individualized treatments for patients with CM with different primary sites.