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.Exploration and practice of multi-campus hospital-associated infection management from the perspective of symbiosis theory
Qun LU ; Tong TONG ; Xiaoyi LI ; Hong WANG ; Kaiwen NI
Chinese Journal of Nosocomiology 2025;35(12):1761-1764
In the multi-campus development and construction of public hospitals,hospital-associated infection man-agement has consistently faced escalating difficulties and challenges.Throughout the long-term exploration and practice,the Second Affiliated Hospital Zhejiang University School of Medicine has adhered to the principles of"integrated planning and deployment,homogeneous and homologous training,information and data sharing,and a focus on professional features".By continuously addressing emerging infection control risk points and weak points,overcoming barriers posed by dispersed human resources,and balancing homogeneity with individualization,the hospital has actively promoted integration and collaborative development across its campuses.This approach has significantly contributed to the sustained improvement of healthcare service capacity and quality across multiple campuses.From the novel perspective of symbiosis theory,this paper analyzes the symbiotic dilemmas in multi-campus hospital-associated infection management,summarizes practical experiences,and explores future direc-tions,aiming to provide references for other public hospitals in multi-campus hospital-associated infection manage-ment.
4.The relationship between urinary arsenic methylation metabolic patterns and the transformation of skin keratinization and pigmentation abnormalities in population exposed to arsenic through drinking water
Xinye LI ; Zhiwei GUO ; Fan ZHAO ; Yuchen GUO ; Mengxin LI ; Lingling HE ; Zhen DI ; Wei SONG ; Kaiwen LIU ; Yu MA ; Yijun LIU ; Chang KONG ; Binggan WEI ; Zhongbing ZHANG
Chinese Journal of Endemiology 2025;44(6):439-444
Objective:To study the relationship between urinary arsenic methylation metabolism patterns and skin keratinization and pigmentation abnormalities in population exposed to arsenic through drinking water.Methods:Using a cross-sectional study method, a survey on endemic arsenic poisoning was conducted among permanent residents of drinking water endemic arsenic poisoning areas in Bayannur City, Inner Mongolia Autonomous Region in 2004 (before water improvement). In 2017 (after water improvement), 71 arsenic exposed individuals were followed up as survey subjects. According to the "Diagnosis of Endemic Arsenism" (WS/T 211-2015), the clinical grading of skin injuries (skin keratinization, pigmentation abnormalities) in the survey subjects was evaluated. Urine samples were collected for detection of arsenic methylation metabolite levels by high-performance liquid chromatography inductively coupled plasma mass spectrometry and calibrated with urinary creatinine. The changes and amplitudes of urinary arsenic methylation indicators before and after water improvement were calculated and analyzed according to the outcome of skin keratinization and pigmentation abnormalities which were divided into reduced, unchanged, and added groups.Results:(1) The changes in urinary total arsenic (TAs), inorganic arsenic (iAs), monomethyl arsenic (MMA), and dimethyl arsenic (DMA) levels in different outcome groups of skin keratinization were compared, and the differences were statistically significant ( H = 9.08, 8.77, 9.28, 8.57, P < 0.05). The changes in urinary TAs, iAs, MMA, DMA levels, iAs percentage (iAs%), DMA percentage (DMA%), and primary methylation index (PMI) in different outcome groups of skin pigmentation abnormalities were compared, and the differences were statistically significant ( H = 8.04, 10.67, 8.29, 9.14, 6.30, 9.10, 7.20, P < 0.05). (2) The comparison of amplitudes in urinary TAs, iAs, MMA, and DMA levels in different outcome groups of skin keratinization showed statistically significant differences ( H = 6.92, 7.34, 6.66, 6.16, P < 0.05). The amplitudes in urinary iAs level, iAs%, DMA%, and PMI in different outcome groups of skin pigmentation abnormalities were compared, and the differences were statistically significant ( H = 7.94, 7.61, 9.95, 7.22, P < 0.05). Conclusion:The changes pattern of urinary TAs, iAs, MMA, DMA, iAs%, DMA%, and PMI in population exposed to arsenic through drinking water is related to the transformation of skin keratinization and pigmentation abnormalities.
5.The relationship between multiple elements in urine and arsenic poisoning in populations exposed to drinking water arsenic in Inner Mongolia Autonomous Region
Yuchen GUO ; Binggan WEI ; Fan ZHAO ; Xinye LI ; Rui WANG ; Shuhui YIN ; Nan WU ; Lingling HE ; Zhen DI ; Kaiwen LIU ; Wei SONG ; Hui WANG ; Zhongbing ZHANG ; Danyu DENG ; Zhiwei GUO
Chinese Journal of Endemiology 2025;44(7):535-542
Objective:To study the relationship between the levels of multiple elements in urine and the risk of arsenic poisoning in populations exposed to drinking water arsenic in Inner Mongolia Autonomous Region (Inner Mongolia).Methods:From April 2023 to January 2024, a case-control study method was used to select 128 individuals with a residence time of ≥10 years in drinking water arsenic exposed areas in Inner Mongolia as study subjects. Eighty-one individuals diagnosed with arsenic poisoning were selected as the case group, and 47 healthy individuals were selected as the control group for urine sample collection and questionnaire survey. Inductively coupled plasma mass spectrometry was employed to determine the levels of 10 elements (chromium, manganese, cobalt, nickel, copper, zinc, arsenic, molybdenum, cadmium and lead) in urine. The levels of each element in urine were divided into four groups ( Q1, Q2, Q3, and Q4 groups) based on quartiles. The associations between the levels of various elements in urine and the risk of arsenic poisoning were studied using binary logistic regression model and restricted cubic spline (RCS). Results:The age of the control group and the case group [ M ( Q1, Q3)] were 61 (53, 69) and 61 (56, 67) years old, respectively. There were 19 and 43 males, and 28 and 38 females, respectively. There was no statistically significant differences in age and and gender composition between the two groups ( Z = - 0.39, P = 0.700; χ 2 = 1.91, P = 0.167). The levels of urinary copper and cadmium of the case group were higher than those of the control group, and the differences were statistically significant ( Z = - 2.66, - 2.16, P < 0.05). The results of univariate logistic regression analysis showed that urinary copper was an influencing factor for arsenic poisoning ( P = 0.017). The results of multivariate logistic regression analysis revealed that after adjusting for covariates, urinary copper and arsenic were independent influencing factors of arsenic poisoning ( P < 0.05). Taking Q1 group as a reference, urinary copper in Q3 group [ OR (95% CI) = 8.23 (1.81, 37.39), P = 0.006] increased the risk of arsenic poisoning, while urinary arsenic in Q2, Q3, and Q4 groups [ OR (95% CI) = 0.24 (0.06, 0.92), 0.12 (0.03, 0.53), 0.15 (0.04, 0.63), P < 0.05] decreased the risk of arsenic poisoning. After adjusting for covariates, RCS did not show a dose-response relationship between urinary copper, urinary arsenic, and arsenic poisoning ( P > 0.05). Conclusion:Urinary arsenic and copper are associated with the risk of arsenic poisoning in the drinking water arsenic exposed areas of Inner Mongolia, copper exposure may contribute significantly to arsenic poisoning.
6.Changes of cardiac structure and function in patients with thoracic lordosis and clinical significance
Quan LI ; Ying ZHANG ; Kaiwen GU
Chinese Journal of Spine and Spinal Cord 2025;35(6):598-605
Objectives:To retrospectively analyze the preoperative imaging and echocardiographic data of pa-tients with thoracic lordosis,and to investigate the relationship between thoracic lordosis and the cardiac structure and function by comparing with normal people.Methods:The imaging and echocardiographic data of patients with thoracic lordosis and normal people obtained between January 2013 and December 2023 were collected and analyzed.According to thoracic angle,the patients were divided into group A of 27 cases[tho-racic lordosis(TL)group,T5-T12≤0°]and group B of 29 cases[red uced thoracic kyphotic(TK)group,0°<T5-T12≤20°].A control group of 29 normal people was set up as group C(normal group,20°<T5-T 12 ≤ 40°).General clinical data including gender,age,height,weight,body mass index(BMI),body surface area(BSA),imaging parameters on X-ray films such as thoracic sagittal and coronal Cobb angles,imaging findings on CT such as spinal penetration index volume(SPIV)and cardiac volume ratio in apical vertebra region(CVRA)were collected,as well as the echocardiographic parameters including left ventricular end-diastolic diameter(LVDd),right ventricular end-diastolic diameter(RVDd),left atrial diameter(LAD),right atrial diameter(RAD),right ven-tricular outflow tract(RVOT),aortic diameter(AO),ascending aortic diameter(AAO),main pulmonary artery diam-eter(MPA),end-diastolic interventricular septal thickness(IVST),left ventricular posterior wall thickness(LVPWT),ejection fraction(EF),fraction shortening(FS),stroke volume(SV),cardiac output(CO),cardiac index(CI),systolic pulmonary artery pressure(SPAP).Statistical analysis was conducted using SPSS 25.0 software for data comparison and correlation analysis between the three groups.Results:SPIV was negatively correlated with sagittal Cobb angle and not correlated with coronal Cobb angle;SPIV was negatively correlated with LVDd,RVDd,LAD,RAD,RVOT,AO,AAO,MPA,IVST,and LVPWT;SPIV wasn't correlated with EF,FS,SV,CO,CI,and SPAP;CVRA was negatively correlated with sagittal Cobb angle and not correlated with coronal Cobb angle;CVRA was negatively correlated with RVDd,IVST,and LVPWT;There was no correla-tion between CVRA and LVDd,LAD,RAD,RVOT,AO,AAO,MPA;CVRA wasn't correlated with EF,FS,SV,CO,CI,and SPAP.Conclusions:SPIV can more effectively reflect the impact of thoracic lordosis on cardiac structure and function than CVRA,and a reduction in thoracic kyphosis angle may exacerbate the workload on cardiac blood vessels.During the orthopedic surgery for patients with thoracic lordosis,significant changes may occur in the structural and functional parameters of the thoracic cavity and cardiac chambers due to factors such as general anesthesia,prone positioning,compression of the sternum and thoracic cage,and muscle relaxant administration,therefore particular attention should be paid to the risks of airway ob-struction and hemodynamic instability.
7.Research progress on assessment tools for health behavior motivation in patients with cardiovascular diseases
Zhifeng ZHANG ; Lei LIU ; Yikang XU ; Daqiu WANG ; Jiayu WANG ; Yu TIAN ; Kaiwen ZHAN ; Siqi SUN ; Manman LI
Journal of Shenyang Medical College 2025;27(2):198-201
Health behavior motivation significantly affects the quality of life of patients with cardiovascular diseases.Assessing the level of health behavior motivation can measure the health behavior of individuals,help to promote the participation rate of cardiac rehabilitation,reduce the readmission rate of patients,and promote patients'healthy lifestyles.This article reviews the content,characteristics and application of assessment tools for health behavior motivation of patients with cardiovascular diseases at home and abroad,with the aim of providing references for the development and application of such tools in China,and offering a basis for scientifically assessing their health behavior motivation level and formulating effective strategies to promote health behavior motivation.
8.Research progress on assessment tools for the treatment burden of patients with chronic diseases
Kaiwen ZHAN ; Lei LIU ; Daqiu WANG ; Jiayu WANG ; Yu TIAN ; Manman LI ; Siqi SUN ; Zhifeng ZHANG
Journal of Shenyang Medical College 2025;27(1):74-78
The number of patients with chronic diseases in China has been increasing year by year,followed by the increase of treatment burden.It is particularly important to effectively evaluate the treatment burden of patients with chronic diseases.This paper reviews the main contents,application scope,advantages and disadvantages of the assessment tools for the treatment burden of patients with chronic diseases at home and abroad,so as to provide references and basis for medical staff to reasonably select assessment tools and conduct relevant clinical research.
9.Characteristics of weight gain during pregnancy and its relationship with gestational diabetes mellitus in women with weight loss in early pregnancy
Kaiwen MA ; Wei ZHENG ; Xianxian YUAN ; Puyang ZHANG ; Lili XU ; Guanghui LI
Chinese Journal of Perinatal Medicine 2025;28(1):36-42
Objective:To investigate the characteristics of weight gain in the mid and late pregnancy of women with early pregnancy weight loss, and the relationship between weight gain and weight gain rate before the diagnosis of gestational diabetes mellitus (GDM) and GDM.Methods:A retrospective study was conducted on 2 614 singleton pregnant women who underwent prenatal care and delivered at Beijing Obstetrics and Gynecology Hospital, Capital Medical University, from January 2014 to December 2021, and whose weight decreased compared to pre-pregnancy weight by 16 weeks of gestation. The rate of weight gain in mid and late pregnancy, also weight gain and weight gain rate at each stage were analyzed. Multivariate logistic regression was used to analyze the impact of total weight gain and weight gain rate at each stage before the diagnosis of GDM on the risk of GDM.Results:The rates of weight gain in mid and late pregnancy for women with early pregnancy weight loss who were underweight, normal weight, overweight, and obese before pregnancy were (0.60±0.15), (0.59±0.18), (0.53±0.20), and (0.42±0.20) kg/week, respectively, all higher than the "Chinese Recommended Standards for Weight Gain During Pregnancy" [which are (0.37-0.56), (0.26-0.48), (0.22-0.37), and (0.15-0.30) kg/week, respectively]. The weight gain rates at each stage of mid and late pregnancy in women with early pregnancy weight loss showed a "bimodal" trend, with the first peak in weight gain rate occurring at 16-20 or 20-24 weeks of gestation [weight gain rates for underweight, normal weight, overweight, and obese women before pregnancy were 0.75 kg/week (0.44-1.00 kg/week), 0.74 kg/week (0.50-1.00 kg/week), 0.63 kg/week (0.39-0.86 kg/week), and 0.50 kg/week (0.25-0.74 kg/week), respectively] and the second peak occurring at 28-32 weeks [weight gain rates for underweight, normal weight, overweight, and obese women before pregnancy were 0.63 kg/week (0.50-1.00 kg/week), 0.63 kg/week (0.38- 0.88 kg/week), 0.60 kg/week (0.25-0.88 kg/week), and 0.50 kg/week (0.22-0.75 kg/week). As of 28 weeks and 36 weeks of gestation, 53.7% (1 404/2 614) and 77.4% (1 946/2 512) of pregnant women, respectively, reached the lower limit of the recommended weight gain for the corresponding gestational weeks. No association was found between insufficient weight gain ( aOR=0.828, 95% CI: 0.639-1.071, P=0.151) or excessive weight gain ( aOR=0.936, 95% CI: 0.598-1.465, P=0.773) before the diagnosis of GDM and the risk of GDM. However, obese women with a weight loss greater than 5% of their pre-pregnancy weight in early pregnancy and a rapid weight gain rate (> P 75) between 16-20 weeks of gestation had an increased risk of developing GDM ( aOR=32.870, 95% CI: 1.625-664.775, P=0.023). Conclusions:In clinical practice, dynamic monitoring of weight changes at various stages of pregnancy in women who lose weight in early pregnancy is recommended. Targeted weight management during mid-pregnancy for women who are obese before pregnancy and experience significant weight loss in early pregnancy may help prevent excessive gestational weight gain and decrease the risk of GDM.
10.Exploration and practice of multi-campus hospital-associated infection management from the perspective of symbiosis theory
Qun LU ; Tong TONG ; Xiaoyi LI ; Hong WANG ; Kaiwen NI
Chinese Journal of Nosocomiology 2025;35(12):1761-1764
In the multi-campus development and construction of public hospitals,hospital-associated infection man-agement has consistently faced escalating difficulties and challenges.Throughout the long-term exploration and practice,the Second Affiliated Hospital Zhejiang University School of Medicine has adhered to the principles of"integrated planning and deployment,homogeneous and homologous training,information and data sharing,and a focus on professional features".By continuously addressing emerging infection control risk points and weak points,overcoming barriers posed by dispersed human resources,and balancing homogeneity with individualization,the hospital has actively promoted integration and collaborative development across its campuses.This approach has significantly contributed to the sustained improvement of healthcare service capacity and quality across multiple campuses.From the novel perspective of symbiosis theory,this paper analyzes the symbiotic dilemmas in multi-campus hospital-associated infection management,summarizes practical experiences,and explores future direc-tions,aiming to provide references for other public hospitals in multi-campus hospital-associated infection manage-ment.


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