1.EGCG Promotes Aβ Clearance of Microglia Through Blockage of the HDAC6-PI3K/AKT/mTOR Signalling Axis Followed by Autophagy Activation
Yu LIN ; Kaiwen HUANG ; Honghai HONG ; Dan ZHU ; Yousheng MO ; Dongli LI ; Shuhuan FANG
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(3):486-497
ObjectiveTo clarify whether epigallocatechin gallate (EGCG) is involved in the clearance of amyloid β-protein (Aβ) and autophagy induction by microglia, so as to explore the potential mechanisms of EGCG in the prevention and treatment of Alzheimer's disease (AD). MethodsSix-month-old APP/PS1 mice were randomly divided into model and EGCG groups, with some additional wild type (WT) mice as the control group, each group consisting of 15 mice. The EGCG group received continuous gavage administration[5 mg/(kg·d)] for 8 weeks, followed by the open field test and Y-maze to assess the learning and memory abilities of the mice. Thioflavin-S staining was used to evaluate the content and distribution of amyloid β-protein (Aβ)in the brain parenchyma of the mice, and immunofluorescence was employed to detect the expression levels of Aβ1-42, glial fibrillary acidic protein (GFAP), and ionized calcium-binding adapter molecule 1 (Iba1) in the hippocampal tissue of the mice. Additionally, N9 mouse microglial cells were induced with 20 µmol/L Aβ1-42, and the cell viability was measured after treatment with different concentrations of EGCG (5 µmol/L, 10 µmol/L, 20 µmol/L). Western blotting was used to detect the levels of Aβ1-42, low density lipoprotein receptor-related protein 1(LRP1), receptor for advanced glycation endproducts (RAGE), amyloid precursor protein (APP), insulin degrading enzyme (IDE), neprilysin (NEP), microtubule associated protein 1 hydrogen chain 3(LC3)-Ⅱ/LC3-Ⅰ, phosphatidylinositol 3-hydroxy kinase(PI3K), p-PI3K, protein kinase B (AKT), p-AKT, mammalian target of rapamycin (mTOR), p-mTOR, and histone deacetylase 6(HDAC6). Finally, through the co-culture of microglial cells and neuronal SH-SY5Y cells, cell viability and Caspase-3 levels were measured to verify the protective effect of EGCG-mediated Aβ clearance on neurons. ResultsEGCG increased the activity time and frequency of APP/PS1 mice in the central area of the open field (P<0.05), and enhanced the percentage of alternation in the Y-maze test (P<0.01); EGCG reduced Aβ deposition in the hippocampal tissue of APP/PS1 mice and increased the number of microglia; in vitro experiments showed that EGCG improved the survival rate of Aβ-induced N9 cells (P<0.01), upregulated RAGE activity (P<0.05), and promoted the internalization and phagocytosis of Aβ (P<0.01). ECGC activated microglial autophagy by downregulating the level of HDAC6 (P<0.05), inhibiting the phosphorylation of PI3K, AKT, mTOR (P<0.001), and increasing the LC3-Ⅱ/LC3-I ratio (P<0.001); EGCG improved the survival rate of SH-SY5Y cells (P<0.05) and reduced the activity of Caspase-3 (P<0.01) by clearing Aβ1-42 through microglia, and had a protective effect on neurons. ConclusionEGCG activates microglial autophagy to clear Aβ by targeting and inhibiting the HDAC6-PI3K/AKT/mTOR axis.
2.Expert consensus on the positioning of the "Three-in-One" Registration and Evaluation Evidence System and the value of orientation of the "personal experience"
Qi WANG ; Yongyan WANG ; Wei XIAO ; Jinzhou TIAN ; Shilin CHEN ; Liguo ZHU ; Guangrong SUN ; Daning ZHANG ; Daihan ZHOU ; Guoqiang MEI ; Baofan SHEN ; Qingguo WANG ; Xixing WANG ; Zheng NAN ; Mingxiang HAN ; Yue GAO ; Xiaohe XIAO ; Xiaobo SUN ; Kaiwen HU ; Liqun JIA ; Li FENG ; Chengyu WU ; Xia DING
Journal of Beijing University of Traditional Chinese Medicine 2025;48(4):445-450
Traditional Chinese Medicine (TCM), as a treasure of the Chinese nation, plays a significant role in maintaining public health. In 2019, the Central Committee of the Communist Party of China and the State Council proposed for the first time the establishment of a TCM registration and evaluation evidence system that integrates TCM theory, "personal experience" and clinical trials (referred to as the "Three-in-One" System) to promote the inheritance and innovation of TCM. Subsequently, the National Medical Products Administration issued several guiding principles to advance the improvement and implementation of this system. Owing to the complexity of its implementation, there are still differing understandings within the TCM industry regarding the positioning of the "Three-in-One" Registration and Evaluation Evidence System, as well as the connotation and value orientation of the "personal experience." To address this, Academician WANG Qi, President of the TCM Association, China International Exchange and Promotion Association for Medical and Healthcare and TCM master, led a group of academicians, TCM masters, TCM pharmacology experts and clinical TCM experts to convene a "Seminar on Promoting the Implementation of the ′Three-in-One′ Registration and Evaluation Evidence System for Chinese Medicinals." Through extensive discussions, an expert consensus was formed, clarifying the different roles of the TCM theory, "personal experience" and clinical trials within the system. It was further emphasized that the "personal experience" is the core of this system, and its data should be derived from clinical practice scenarios. In the future, the improvement of this system will require collaborative efforts across multiple fields to promote the high-quality development of the Chinese medicinal industry.
3.Application of CAD/CAM Technology in the Teaching of Inlay Production
Yingying XIANG ; Hao HUANG ; Xuelin LI ; Zhigang XIA ; Kaiwen DUAN ; Fei SONG
Journal of Kunming Medical University 2024;45(2):166-169
Objective To study the application value of CAD/CAM technology in the teaching of inlay manufacturing.Methods A total of 60 undergraduates interned in the Department of Stomatology,Yan'an Hospital,Kunming Medical University were randomly divided into an experimental group(n=30)and a control group(n=30).We selected appropriate clinical cases for students to prepare for mandibular molar's proximal occlusal inlays.The instructor guided the results of the first preparation in different ways,and the students made the second modification and preparation,and the assessment team scored and evaluated the five aspects of the final preparation,the shape of the preparation,the shape of the occlusal surface,the dovetail retention,and the adjacent surface.Results The scores of all detection indexes in the experimental group were higher than those in the control group(P<0.05).Conclusion The application of CAD/CAM technology in inlay manufacturing teaching can effectively improve students'clinical hands-on ability and achieve better teaching effects than traditional teaching methods.
4.Application of metal-organic frameworks in implant surface modification
Chinese Journal of Tissue Engineering Research 2024;28(5):783-788
BACKGROUND:In recent years,metal-organic frameworks have been widely used in the biomedical field because of their unique properties,and metal-organic frameworks can be applied to implant surface modification for improving their biological properties and the surgery's success rate. OBJECTIVE:To introduce metal-organic frameworks commonly used in implant surface modification and the preparation and action mechanism of surgical implants modified by metal-organic frameworks. METHODS:The articles concerning metal-organic frameworks used in implant surface modification published from 2010 to 2023 were searched on PubMed,Web of Science and CNKI.Finally,64 articles were included for review. RESULTS AND CONCLUSION:(1)Metal-organic frameworks have the properties of high porosity,large specific surface area,and diverse spatial structure.As bioactive material,metal-organic frameworks have attracted much attention in tissue engineering and regenerative medicine.(2)The metal-organic frameworks commonly used in the field of implant surface modification include three types.Zeolitic imidazolate frameworks are commonly used as carriers,carrying various drugs and biomolecules.The MIL series are suitable for drug carriers and nanoenzymes.Bio-metal-organic frameworks have many applications because of their diverse structure and are characterized by excellent biosafety.(3)The preparation of implant materials modified by metal-organic frameworks can be mainly divided into two types:one is to incorporate metal-organic frameworks into pretreated implants;the other is to synthesize metal-organic frameworks in situ on pretreated implants.(4)Metal-organic frameworks on the implant surface could release their components,load drugs,catalyze active reactions,or combine with other materials,giving implants antibacterial and anti-inflammatory characteristics and promoting osseointegration.The preparation method of metal-organic framework coatings needs further improvement,and the metabolism and distribution of metal-organic framework coatings should be deeply explored,and its clinical application should be actively promoted.
5.Three laboratory direct test methods for maximal oxygen uptake:Comparison,regression analysis and applications
Ling LIN ; Wenteng WU ; Jiaming LUO ; Kaiwen FAN ; Huaye WANG ; Zhiguang LI ; Xiaoping DUAN
Chinese Journal of Sports Medicine 2024;43(1):29-38
Objective To compare the discrepancies among results of three commonly used laboratory direct test methods for maximal oxygen uptake(VO2max),explore their linear regression relationships,mutual predictability and comparability.Methods Using a quasi-experimental design of cluster sampling and within-group interaction design,20 male cross-country skiers were tested for VO2max using the Bruce protocol(Method 1),90-second incremental load exercise on power bicycle(Method 2),and 1-minute incremental load exercise on treadmill(Method 3),with an interval of one week.The indepen-dent and dependent variable were the three VO2max test methods and the VO2max,respectively.Results Significant differences were found in the average VO2max of the three test results,with the value mea-sured by Method 1 ranking the first,followed by that assessed by Method 3 and Method 2(P<0.05).Moreover,the frequency of individual differences in the results of the three methods showed that the VO2max of Method 1 was about 6 and 3 ml/min·kg higher than that measured by Method 2 and 3.However,at the same treadmill speed,the average blood lactate evaluated using Method 3 was higher than Method 1,and the speed reached aerobic and anaerobic thresholds about one speed unit(1 km/h)lower than Method 1.Meanwhile,linear regression analyses of the test results between Method 1 and 2,as well as Method 1 and 3 showed that both the regression models and coefficients were statis-tically significant(P<0.001),with the R-squared values of 9.25 and 9.05,respectively.Conclusion The Bruce protocol performs best in assessing the maximum value of the athlete's VO2max phase,whose results have linear regression relationships with the other two methods,and can be used for pre-dicting their results.Moreover,athletes of different events and levels can choose different VO2max test methods accordingly.Lastly,the speed and heart rate ranges corresponding to the aerobic and anaero-bic thresholds can serve as an effective and convenient method to control the training intensity.
6.Theory and Analysis of Pharmacokinetic and Chromatokinetics Dose-time Characterization Methods in Traditional Chinese Medicine
Ru QIAO ; Peng HE ; Qijun HE ; Haiying LI ; Meifeng XIAO ; Kaiwen DENG ; Fuyuan HE
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(22):178-186
ObjectiveTo establish a theoretical system of pharmacokinetic and spectrokinetic dose-time characterization of traditional Chinese medicine(TCM). By analyzing the pharmacokinetic and spectrokinetic behaviors of Lonicerae Flos, Houttuyniae Herba injection, Lonicerae Japonicae Flosand Buyang Huanwutang, this paper compared the similarities and differences of the three methods for characterizing the dose-time relationship, namely half-life, statistical moment and statistics, in order to find the most suitable method for characterizing the relationship. MethodTen mice were randomly selected from 100 Kunming mice as the blank group, and the remaining mice were coated with xylene in the auricle to establish the acute inflammation model of ear swelling. After successful modeling, the mice were gavaged with aqueous extract of Lonicerae Flos(30 g∙kg-1), and the blank group was gavaged with an equal volume of normal saline. The plasma of mice was collected at different time points to determine the content changes of components. At the same time, the pharmacokinetic results of Houttuyniae Herba injection, Lonicerae Japonicae Flos and Buyang Huanwutang were included, and the pharmacokinetic and spectrokinetic parameters were calculated. Then the difference in the time of calculating 95% total component content of metabolism by half-life method, statistical moment method and statistical method was compared. ResultOn the basis of the half-life method, the mathematical expressions of statistical moment method and statistical method suitable for the characterization of dose-time relationship of multi-component system of TCM were established. The results showed that the pharmacokinetic parameters of the individual components in Lonicerae Flos varied, with cryptochlorogenic acid and rutin showing a two-compartment model and the other components showing a one-compartment model. After calculation of spectrokinetic similarity, the metabolic patterns among the components contained in Houttuyniae Herba injection, Lonicerae Japonicae Flos, Lonicerae Flos and Buyang Huanwutang were different and varied greatly in vivo. The time to metabolize 95% of the total components of the four research subjects in vivo was calculated by the half-life method, statistical moment method and statistical method, and it was found that the difference between statistical moment method and half-life method was large, and the difference between statistical moment method and statistical method was small. ConclusionStatistical method not only reflects the characteristics of statistical moment method, characterizes the dispersion degree of each component, but also can be associated with fingerprint to form spectrokinetics, characterizing the dose-time relationship of 95% of drug components, which is a more desirable method to characterize the dose-time relationship of the component groups in TCM.
7.Progress in the application of deep learning in prognostic models for non-small cell lung cancer
Ruikang ZHONG ; Jinghua LI ; Ximing LIN ; Xueni FANG ; Kaiwen HU ; Tian ZHOU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(09):1345-1350
Non-small cell lung cancer is one of the cancers with the highest incidence and mortality rate in the world, and precise prognostic models can guide clinical treatment plans. With the continuous upgrading of computer technology, deep learning as a breakthrough technology of artificial intelligence has shown good performance and great potential in the application of non-small cell lung cancer prognosis model. The research on the application of deep learning in survival and recurrence prediction, efficacy prediction, distant metastasis prediction, and complication prediction of non-small cell lung cancer has made some progress, and it shows a trend of multi-omics and multi-modal joint, but there are still shortcomings, which should be further explored in the future to strengthen model verification and solve practical problems in clinical practice.
8.Research progress in the effective components and mechanism of medicinal and food homologous Chinese materia medica in the prevention and treatment of diabetic cardiomyopathy
Wei LI ; Pengyu YAO ; Ping WANG ; Meng WANG ; Kaiwen DING
International Journal of Traditional Chinese Medicine 2024;46(7):952-956
It is found that medicinal and food homologous Chinese materia medica such as Astragali Radix, Ginseng Radix et Rhizoma, Citri Reticulatae Pericarpium, Citri Fructus, Citri Sarcodactylis Fructus, Citri Exocarpium Rubrum, Curcumae Longae Rhizoma, Gardeniae Fructus, Glycyrrhizae Radix et Rhizoma, Puerariae Lobatae Radix, Portulacae Herba, Lycii Fructus and Piperis Longi Fructus have significant effects on the prevention and treatment of diabetic cardiomyopathy. Active components, including Astragalus polysaccharide, Astragalus agaloside, ginsenoside Rb1, ginsenoside Rg1 and naringin can prevent and treat myocardial damage in diabetes mellitus through mechanisms of anti-inflammation, anti-oxidative stress, inhibition of apoptosis, regulation of autophagy, anti-fibrosis, and regulation of energy metabolism, etc.
9.Policy analysis on the infection prevention and control of medical alliance in China
Qun LU ; Zhenwei LI ; Yuzheng ZHANG ; Feiyu WU ; Kaiwen NI
Chinese Journal of Hospital Administration 2024;40(8):635-639
Objective:To quantitatively analyze infection prevention and control policy texts related to medical alliance, aiming to provide reference for further policy improvement.Methods:with the " medical alliance" and " infection prevention and control" as keywords, relevant policy documents issued from January 2015 to March 2023 were searched on the Chinese government website, the official website of the National Health Commission, and the Peking University law database. Content analysis method was used to quantitatively analyze policy texts from two dimensions: policy tools (supply oriented, environmental oriented, demand oriented) and systems theory (management, service, human resources, and financing systems as internal subsystems, while political, economic, social, and technological systems as external subsystems).Results:A total of 91 infection prevention and control policy documents related to medical alliance were included, and 199 codes were obtained. There were 114, 78, and 7 codes for environmental oriented, supply oriented, and demand oriented policy tools, respectively; among the demand oriented tools, there were only 1 code for government purchases, 1 code for price subsidies, and 5 codes for demonstration project sub tools, respectively. The internal subsystem had a total of 119 codes, with only 2 codes related to the fundraising system; and the external subsystem had a total of 80 codes, with the least 10 codes related to the technical system.Conclusions:The structure of infection prevention and control policy tools in China′s medical alliance needed to be optimized, and the application of demand oriented policy tools was insufficient. It is necessary to strengthen the use of pull tools such as government purchases, price subsidies, and demonstration projects. At the same time, it is necessary to improve the construction of internal and external systems, especially in terms of fundraising and technology systems, to enhance the overall effectiveness of the medical alliance′s infection prevention and control system.
10.Construction of risk prediction model of heart failure in patients with coronary heart disease based on LASSO regression
Yikang XU ; Jingru MA ; Yang YANG ; Lei LIU ; Zhifeng ZHANG ; Siqi SUN ; Manman LI ; Kaiwen ZHAN
China Modern Doctor 2024;62(28):1-5,46
Objective To analyze the risk factors of heart failure in patients with coronary heart disease(CHD),and to construct and verify a nomogram prediction model for the risk of heart failure in patients with CHD.Methods The clinical data of 453 patients with CHD who were hospitalized in the Second Affiliated Hospital of Shenyang Medical College from January to December 2022 were retrospectively analyzed,including 278 patients with CHD combined with heart failure and 175 patients without heart failure.The patients were divided into training group(318 cases)and validation group(135 cases)according to the ratio of 7:3.R software was applied to perform LASSO regression to screen the risk factors,and Logistic regression to establish a prediction model and construct a nomogram.The calibration curve and receiver operating characteristic(ROC)curve were used to evaluate the calibration and discrimination of the model.Results LASSO regression analysis ultimately screened five risk factors from 22 variables,and Logistic regression results showed that age,smoking,history of myocardial infarction,New York Heart Association(NYHA)cardiac function class Ⅳ,and left ventricular ejection fraction(LVEF)were all independent risk factors for heart failure in CHD patients(P<0.05).The model formula was Z=-2.927+0.045 × age+0.886 × smoking+0.808 × history of myocardial infarction-2.829 × NYHA cardiac function class Ⅳ+0.037×LVFF.Internal validation of the model showed that area under the curve was 0.727(95%CI:0.588-0.752),the sensitivity was 40.4%,the specificity was 84.3%,and the Youden index was 0.247.According to the calibration curve,the predicted value of the calibration curve was highly consistent with the actual value,and the Brier score was 0.106.Conclusion The risk prediction model for heart failure in patients with CHD based on LASSO regression has good discrimination and prediction efficiency,which can be used as an evaluation tool for medical staff to predict the risk of patients.


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