Objective To explore the mechanism by which puerarin alleviates the cardiotoxicity induced by doxorubicin in myocardial cells. Methods Cells in the logarithmic growth phase were divided into normal control group,model group,low-(20 mmol·L-1),medium-(40 mmol·L-1) and high-(80 mmol·L-1) dose puerarin groups,and positive control group(captopril,1 mmol·L-1). Except for the normal control group,the other groups were co-incubated with 5 mmol·L-1 doxorubicin. Cell viability was assessed using CCK-8 and lactate dehydrogenase (LDH) assays. ROS levels were detected using a ROS probe. Autophagy flux was detected by transfection with HBAD-mcherry-EGFP-LC3 adenovirus. Western Blot was used to measure the protein expression levels of Beclin-1,LC3,p62,p-AMPKα,and AMPKα. Lysosomal function was assessed using a lysosomal probe. Immunofluorescence was used to detect the relative intensity and co-localization of ASMase and LAMP1. Molecular docking analysis was performed to predict the binding capacity of PUE with ASMase. Differential gene expression was analyzed by gene set enrichment analysis. Results Compared to the normal control group,the model group showed reduced cell viability (P<0.01),increased release levels of LDH and ROS (P<0.05,P<0.01),increased number of autophagosomes (P<0.01),and decreased number of autophagic lysosomes (P<0.05). Beclin-1 protein expression and LC3-II/LC3-I ratio decreased(P<0.01),but p62 protein expression increased(P<0.01). Fluorescence intensity of lysosome decreased(P<0.01),whereas fluorescence intensity of ASMase increased(P<0.01). Immunofluorescence co-localization of ASMase and LAMP1 increased (P<0.01),the ratio of p-AMPKα/AMPKα decreased(P<0.05). Compared to the model group,the high-dose puerarin group showed a rebound in cell viability (P<0.05). The medium-and high-dose puerarin groups showed a decreasing trend in LDH level (P<0.05),and all puerarin groups showed a decreasing trend in ROS level (P<0.01). The number of autophagosomes in high-dose puerarin group reduced (P<0.01). The number of autophagic lysosomes in all puerarin groups increased (P<0.05,P<0.01). The high-dose puerarin group showed increased expression of Beclin-1 (P<0.05) and LC3-II/LC3-I ratio,and decreased p62 expression (P<0.01). All puerarin groups showed increased lysosomal fluorescence intensity (P<0.05,P<0.01). The medium-and high-dose puerarin groups showed a decrease in ASMase fluorescence intensity(P<0.05),a reduction in the immunofluorescence co-localization of ASMase with LAMP1 (P<0.01),and an increase in the p-AMPKα/AMPKα ratio (P<0.01). Molecular docking analysis discovered puerarin showed a binding energy of-8.6 kcal·mol-1 with ASMase. Gene enrichment analysis indicated that the differentially expressed genes in the doxorubicin cardiotoxicity model were related to apoptosis,autophagy,and lysosomal function. Conclusion Puerarin can alleviate doxorubicin-induced cardiotoxicity in myocardial cells and protect myocardial cells by regulating autophagy through AMPK/ASMase,as well as restoring autophagic flux.

Objective:To explore the clinical application value of a deep learning algorithm-based ultrasound biomicroscopy (UBM) image analysis system for primary angles-closure glaucoma (PACG) anterior located ciliary body.Methods:A diagnostic test study was conducted.A total of 2 132 UBM images from 726 eyes of 378 PACG patients who underwent UBM examination were collected at Renmin Hospital of Wuhan University from August 2022 to December 2023.The dataset was divided into a training set of 1 599 images and a test set of 533 images, and a deep learning algorithm was employed to construct a model.An additional 334 UBM images from 101 eyes of 69 PACG patients treated at Huangshi Aier Eye Hospital were selected to conduct external testing.A separate set of another 110 UBM images were selected for a human-machine competition to compare the accuracy and speed between anterior located ciliary body evaluation system and three senior ophthalmologists.Furthermore, eight junior ophthalmologists assessed the 110 UBM images independently without and with the assistance of the model, and the differences between the two evaluations were analyzed to assess the assisstance effect of the model.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Renmin Hospital of Wuhan University (No.WDRY-2022-K109).Results:The model achieved an accuracy of 93.43% for anterior located ciliary body identification in the internal test set, with a sensitivity of 84.30% and a specificity of 97.78%.The model also performed well on the external test set with an accuracy of 92.81%.In the human-machine competition, the model's accuracy was comparable to that of the senior ophthalmologists and outperformed two of the three senior ophthalmologists.The average total time of the three senior ophthalmologists was 726.73 seconds, approximately 12.47 times longer than the model's 58.30 seconds.With model assistance, the diagnostic accuracy of the eight junior ophthalmologists was 86.71%, which was significantly higher than 76.25% without model assistance ( χ2=-7.550, P<0.001).And the image evaluation time was (714.91±213.82)seconds, which was significantly lower than (987.90±238.56)seconds without model assistance ( t=2.774, P<0.05). Conclusions:The UBM image analysis system based on a deep learning algorithm demonstrates high accuracy in diagnosing anterior located ciliary body in PACG and provides a strong support for the UBM image recognition training of junior ophthalmologists.

Demyelination of the central nervous system often occurs in neurodegenerative diseases， such as multiple sclerosis （MS）. The myelin sheath， a layer of myelin membrane wrapping the axon， plays a role in the rapid conduction and metabolic coupling of impulses for neurons. The exposure of the axon will lead to axonal degeneratio， and further neuronal degeneration， which is the main cause of dysfunction and even disability in patients with demyelinating neurodegenerative diseases. In addition to the demyelination of mature myelin sheath， remyelination disorder is also one of the major reasons leading to the development of the diseases. The myelin sheath is composed of oligodendrocytes （OLs） derived from oligodendrocyte progenitor cells （OPCs） which are differentiated from neural stem cells （NSCs）. The process of myelin regeneration， i.e.， remyelination， is the differentiation of NSCs into OLs. Recent studies have shown that this process is regulated by a variety of genes. MicroRNAs， as important regulators of neurodegenerative diseases， form a complex regulatory network in the process of myelin regeneration. This review summarizes the main molecular pathways of myelin regeneration and microRNAs involved in this process and classifies the mechanisms and targets. This review is expected to provide a theoretical reference for the future research on the treatment of demyelinating diseases by targeting the regulation of microRNAs.

Objective:To construct an artificial intelligence (AI)-assisted system based on deep learning for corneal in vivo confocal microscopy (IVCM) image recognition and to evaluate its value in clinical applications. Methods:A diagnostic study was conducted.A total of 18 860 corneal images were collected from 331 subjects who underwent IVCM examination at Renmin Hospital of Wuhan University and Zhongnan Hospital of Wuhan University from May 2021 to September 2022.The collected images were used for model training and testing after being reviewed and classified by corneal experts.The model design included a low-quality image filtering model, a corneal image diagnosis model, and a 4-layer identification model for corneal epithelium, Bowman membrane, stroma, and endothelium, to initially determine normal and abnormal corneal images and corresponding corneal layers.A human-machine competition was conducted with another 360 database-independent IVCM images to compare the accuracy and time spent on image recognition by three senior ophthalmologists and the AI system.In addition, 8 trainees without IVCM training and with less than three years of clinical experience were selected to recognize the same 360 images without and with model assistance to analyze the effectiveness of model assistance.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Renmin Hospital of Wuhan University (No.WDRY2021-K148).Results:The accuracy of this diagnostic model in screening high-quality images was 0.954.Its overall accuracy in identifying normal/abnormal corneal images was 0.916 and 0.896 in the internal and external test sets, respectively.Its accuracy reached 0.983, 0.925 in the internal test sets and 0.988, 0.929 in the external test sets in identifying corneal layers of normal and abnormal images, respectively.In the human-machine competition, the overall recognition accuracy of the model was 0.878, which was similar to the average accuracy of the three senior physicians and was approximately 300 times faster than the experts in recognition speed.Trainees assisted by the system achieved an accuracy of 0.816±0.043 in identifying corneal layers of normal and abnormal images, which was significantly higher than 0.669±0.061 without model assistance ( t=6.304, P<0.001). Conclusions:A deep learning-based assistant system for corneal IVCM image recognition is successfully constructed.This system can discriminate normal/abnormal corneal images and diagnose the corresponding corneal layer of the images, which can improve the efficiency of clinical diagnosis and assist doctors in training and learning.

ObjectiveTo investigate the effects of Jiaohong pills （JHP） and its prescription， Pericarpium Zanthoxyli （PZ） and Rehmanniae Radix （RR） cognitive dysfunction in scopolamine-induced Alzheimer's disease （AD） mice and its mechanism through pharmacodynamic and metabolomics study. MethodThe animal model of AD induced by scopolamine was established and treated with PZ， RG and JHP， respectively. The effects of JHP and its formulations were investigated by open field test， water maze test， object recognition test， avoidance test， cholinergic system and oxidative stress related biochemical test. Untargeted metabolomics analysis of cerebral cortex was performed by ultra-performance liquid chromatography-Quadrupole/Orbitrap high resolution mass spectrometry （UPLC Q-Exactive Orbitrap MS）. ResultThe behavioral data showed that， compared with the model group， the discrimination indexes of the high dose of JHP， PZ and RR groups was significantly increased （P<0.05）. The staging rate of Morris water maze test in the PZ， RR， high and low dose groups of JHP was significantly increased （P<0.05， P<0.01）， the crossing numbers in the PZ， JHP high and low dose groups were significantly increased （P<0.05， P<0.01）； the number of errors in the avoidance test were significantly reduced in the PZ and high-dose JHP groups （P<0.01）， and the error latencies were significantly increased in the JHP and its prescription drug groups （P<0.01）. Compared with the model group， the activities of acetylcholinesterase in the cerebral cortex of the two doses of JHP group and the PZ group were significantly increased （P<0.05， P<0.01）， and the activity of acetylcholinesterase in the high-dose JHP group was significantly decreased （P<0.05）， and the level of acetylcholine was significantly increased （P<0.01）. At the same time， the contents of malondialdehyde in the serum of the two dose groups of JHP decreased significantly （P<0.05， P<0.01）. The results of metabolomics study of cerebral cortex showed that 149 differential metabolites were identified between the JHP group and the model group， which were involved in neurotransmitter metabolism， energy metabolism， oxidative stress and amino acid metabolism. ConclusionJHP and its prescription can antagonize scopolamine-induced cognitive dysfunction， regulate cholinergic system， and reduce oxidative stress damage. The mechanism of its therapeutic effect on AD is related to the regulation of neurotransmitter， energy， amino acid metabolism， and improvement of oxidative stress.

Dementia in traditional Chinese medicine （TCM） mainly presents amnesia and dullness. Alzheimer's disease and vascular dementia belong to the category of dementia in TCM. These progressive neurological diseases have a complex etiology and a long course， and the drugs that can reverse the disease course remain to be developed. Therefore， early intervention plays a vital role in delaying the disease progression. Apathy refers to a lack of motivation that leads to the attenuation or disappearance of goal-directed behaviors， cognitive functions， and emotional responses. Clinical studies have suggested that apathy exists in the early stage of a variety of neurodegenerative diseases， being one of the key symptoms to the early diagnosis of dementia. The severity of apathy is related to the severity of dementia. Therefore， early diagnosis and treatment of apathy are of great significance to the prevention and treatment of dementia. The preclinical research on apathy in dementia is still in its infancy， and the systematic evaluation method has not been prescribed. The clinical diagnosis and treatment are also in the exploratory stage， and the complex pathophysiological mechanisms of apathy and dementia development have not been fully elucidated. This article reviews the research progress of apathy in dementia， the apathetic behaviors of dementia animal models， the behaviors of patients with apathy， and the treatment methods in recent years and summarizes the research status of apathy in dementia. This review aims to provide a theoretical basis for exploring the behavior of apathy in dementia and conducting preclinical research and evaluation of the pathogenesis and to lay a foundation for the treatment of apathy in dementia.

Traditional Chinese medicine （TCM） has a long history of application in China and has consistently played a vital role in treating diseases and saving lives. TCM prescriptions （compounds） constitute the primary form of clinical TCM treatment and significantly differ from western medicine （chemicals） due to the diverse composition and chemical constituents of TCM （compounds）. Nevertheless， the potential multi-component， multi-target， and multi-pathway action characteristics of TCM prescriptions also demonstrate their possible （complementary） therapeutic advantages when compared with single-component chemical drugs. Therefore， driven by the development of modern science and technology and the demands of the modernization and internationalization of TCM， modern theories regarding the complexity of TCM prescription effects have been continuously proposed： Different from the abstract language of traditional prescription theory， the modern TCM prescription theory is more inclined to illustrate the connotation of prescription compatibility concretely and vividly from an experimental and scientific perspective. In this paper， new theories on the complexity of TCM prescriptions proposed in recent years are summarized to provide research references and ideas for the greater role of TCM prescriptions and a better scientific understanding.

In order to understand the knowledge, attitude and practice (KAP) of vaccination against influenza, pneumonia, human papillomavirus (HPV), herpes zoster (HZ), COVID-19, and hepatitis B among staff of vaccination units in Shandong Province, a sample survey was conducted among 797 staffs of adult vaccination units in 12 counties (cities and districts) of Shandong Province from August to September 2022. The results showed that the respondents had the highest total score of knowledge and attitude for the COVID-19 vaccine, with the M ( Q1, Q3) of 23 (20, 25) and 10 (10, 10), respectively, and had the lowest score of knowledge and attitude for the herpes zoster vaccine, with the M ( Q1, Q3) of 19 (15, 22) and 8 (8, 10), respectively. The vaccine-related knowledge point"vaccine applicable population"had the highest score, with the M (Q1, Q3) of 26 (23, 30). The "contraindications/adverse reactions" and "adverse reaction management" had the lowest score, with the M (Q1, Q3) of 24 (20, 29) and 24 (20, 28), respectively. About 89.71% of respondents received one adult vaccine within two years at least. The principal driver for vaccination of 53.58% of recipients was their understanding of vaccines, which was"it was necessary to receive the vaccine". About 66.00% of respondents who had not received any adult vaccine in the past two years had insufficient awareness of the necessity of vaccination and believed that they were in good health and did not need to receive it. In summary, the staff of adult vaccination units in Shandong Province have a poor understanding of the herpes zoster vaccine in terms of vaccines and a relatively poor understanding of"contraindications/adverse reaction and management"in adult vaccination knowledge points.

In order to understand the knowledge, attitude and practice (KAP) of vaccination against influenza, pneumonia, human papillomavirus (HPV), herpes zoster (HZ), COVID-19, and hepatitis B among staff of vaccination units in Shandong Province, a sample survey was conducted among 797 staffs of adult vaccination units in 12 counties (cities and districts) of Shandong Province from August to September 2022. The results showed that the respondents had the highest total score of knowledge and attitude for the COVID-19 vaccine, with the M ( Q1, Q3) of 23 (20, 25) and 10 (10, 10), respectively, and had the lowest score of knowledge and attitude for the herpes zoster vaccine, with the M ( Q1, Q3) of 19 (15, 22) and 8 (8, 10), respectively. The vaccine-related knowledge point"vaccine applicable population"had the highest score, with the M (Q1, Q3) of 26 (23, 30). The "contraindications/adverse reactions" and "adverse reaction management" had the lowest score, with the M (Q1, Q3) of 24 (20, 29) and 24 (20, 28), respectively. About 89.71% of respondents received one adult vaccine within two years at least. The principal driver for vaccination of 53.58% of recipients was their understanding of vaccines, which was"it was necessary to receive the vaccine". About 66.00% of respondents who had not received any adult vaccine in the past two years had insufficient awareness of the necessity of vaccination and believed that they were in good health and did not need to receive it. In summary, the staff of adult vaccination units in Shandong Province have a poor understanding of the herpes zoster vaccine in terms of vaccines and a relatively poor understanding of"contraindications/adverse reaction and management"in adult vaccination knowledge points.

Financial toxicity has a significant impact on the material, psychological, health, and behavior of colorectal cancer patients, leading to poor prognosis and even death. This article reviews the generation, current status, evaluation tools, influencing factors, and response strategies of financial toxicity in colorectal cancer patients, in order to provide reference for domestic research on financial toxicity.