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.Comparison of Therapeutic Effect of Different Preparation Processes of Baihe Dihuangtang on Depressed Mice Based on Q-Marker
Yan LIU ; Jiameng LIU ; Jiahui PENG ; Dan LI ; Shengjun MA ; Jingfan YANG ; Yu FU ; Guangwei ZHU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):159-167
ObjectiveBased on modern analytical techniques and a depressed mouse model established by chronic unpredictable mild stress(CUMS), to evaluate the quality marker(Q-Marker) and pharmacodynamic difference of Baihe Dihuangtang prepared by different processes. MethodsHigh performance liquid chromatography(HPLC) was used to establish the characteristic profiles of Baihe Dihuangtang, and determine the content of Q-Marker in the samples prepared by ancient and modern processes. Seventy C57BL/6J mice were randomly divided into the normal group, model group, fluoxetine group(3 mg·kg-1), low and high dose groups of ancient process(6.5, 26 g·kg-1), and low and high dose groups of modern process(6.5, 26 g·kg-1), with 10 mice in each group. Except for the normal group, CUMS was used to induce depression in mice from the other groups for 28 d. After successful modeling, administration groups were given the corresponding drugs by gavage every day, and the normal and model groups were given an equal volume of pure water by gavage for 21 consecutive days. Change in body mass of mice was recorded, tail suspension test and open field test were used to evaluate the depressive behavior of mice, and enzyme-linked immunosorbent assay(ELISA) was employed to determine the contents of tumor necrosis factor-α(TNF-α), interleukin(IL)-1β and IL-6 in serum. ResultsCharacteristic profiles of Baihe Dihuangtang prepared by the two processes were established, the similarity between the two was 0.951, and 8 characteristic peaks were recognized with the reference peak of regaloside A. The results of quantitative analysis showed that the Q-Marker content was similar in Baihe Dihuangtang prepared by ancient and modern processes. The results of pharmacodynamics showed that, compared with the normal group, the model group showed increased immobility time in the tail suspension test, reduced total movement distance in the open field test, and elevated IL-1β, IL-6 and TNF-α levels in the serum(P<0.01). Compared with the model group, the behavioral indicators of mice in the Baihe Dihuangtang treatment group were significantly improved in terms of tail suspension time and open field exercise, and the levels of IL-1β, IL-6 and TNF-α in serum were significantly reduced(P<0.05, P<0.01). Baihe Dihuangtang prepared by the two processes both had antidepressant effects, and the difference between the two was not statistically significant in improving depressive symptoms. ConclusionQ-Marker of Baihe Dihuangtang prepared by modern and ancient methods are equivalent in content, and the pharmacological effects are consistent, indicating that dried Lilii Bulbus can replace fresh products in the preparation of Baihe Dihuangtang. This study provides a scientific basis for the development of new drugs of Baihe Dihuangtang and a reference for its rational application and clinical use.
3.Comparison of Therapeutic Effect of Different Preparation Processes of Baihe Dihuangtang on Depressed Mice Based on Q-Marker
Yan LIU ; Jiameng LIU ; Jiahui PENG ; Dan LI ; Shengjun MA ; Jingfan YANG ; Yu FU ; Guangwei ZHU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):159-167
ObjectiveBased on modern analytical techniques and a depressed mouse model established by chronic unpredictable mild stress(CUMS), to evaluate the quality marker(Q-Marker) and pharmacodynamic difference of Baihe Dihuangtang prepared by different processes. MethodsHigh performance liquid chromatography(HPLC) was used to establish the characteristic profiles of Baihe Dihuangtang, and determine the content of Q-Marker in the samples prepared by ancient and modern processes. Seventy C57BL/6J mice were randomly divided into the normal group, model group, fluoxetine group(3 mg·kg-1), low and high dose groups of ancient process(6.5, 26 g·kg-1), and low and high dose groups of modern process(6.5, 26 g·kg-1), with 10 mice in each group. Except for the normal group, CUMS was used to induce depression in mice from the other groups for 28 d. After successful modeling, administration groups were given the corresponding drugs by gavage every day, and the normal and model groups were given an equal volume of pure water by gavage for 21 consecutive days. Change in body mass of mice was recorded, tail suspension test and open field test were used to evaluate the depressive behavior of mice, and enzyme-linked immunosorbent assay(ELISA) was employed to determine the contents of tumor necrosis factor-α(TNF-α), interleukin(IL)-1β and IL-6 in serum. ResultsCharacteristic profiles of Baihe Dihuangtang prepared by the two processes were established, the similarity between the two was 0.951, and 8 characteristic peaks were recognized with the reference peak of regaloside A. The results of quantitative analysis showed that the Q-Marker content was similar in Baihe Dihuangtang prepared by ancient and modern processes. The results of pharmacodynamics showed that, compared with the normal group, the model group showed increased immobility time in the tail suspension test, reduced total movement distance in the open field test, and elevated IL-1β, IL-6 and TNF-α levels in the serum(P<0.01). Compared with the model group, the behavioral indicators of mice in the Baihe Dihuangtang treatment group were significantly improved in terms of tail suspension time and open field exercise, and the levels of IL-1β, IL-6 and TNF-α in serum were significantly reduced(P<0.05, P<0.01). Baihe Dihuangtang prepared by the two processes both had antidepressant effects, and the difference between the two was not statistically significant in improving depressive symptoms. ConclusionQ-Marker of Baihe Dihuangtang prepared by modern and ancient methods are equivalent in content, and the pharmacological effects are consistent, indicating that dried Lilii Bulbus can replace fresh products in the preparation of Baihe Dihuangtang. This study provides a scientific basis for the development of new drugs of Baihe Dihuangtang and a reference for its rational application and clinical use.
4.Study on the characteristic chromatogram of Shexiang Jiegu Capsule and determination of seven components by HPLC
Xiaocui YU ; Xiwen WANG ; Guiying ZHANG ; Junwei XU ; Yuwei ZHU ; Dan HU
Journal of Pharmaceutical Practice and Service 2025;43(8):395-399
Objective To establish the characteristic atlas of Shexiang Jiegu Capsule and determine the contents of seven active components (hydroxysafflor Yellow A, paeoniflorin, ferulic acid, naringin, ligustilide, catechin, epicatechin). Methods Octadecyl silane bonded silica gel was used as the filling agent, the mobile phase was composed of methanol-0.05% phosphoric acid by gradient elution, the detection wavelength was 245 nm, flow rate was 1.0 ml/min, column temperature was 30℃. The similarity of the fifteen batches of sample was evaluated in line with the TCM Chromatographic Fingerprint (2012 edition), and the contents of seven active components were determined. Results The HPLC fingerprint of Shexiang Jiegu Capsules was established. The similarity of fingerprint between fifteen batches of samples and control fingerprint was between 0.893 and 0.992. The results of methodological investigation for the determination of seven active components in fifteen batches of samples all met the requirements. Conclusion The established characteristic atlas of Shexiang Jiegu Capsules had high specificity and good repeatability, which could provide scientific basis for quality control of Shexiang Jiegu Capsules.
5.Ameliorative effects of Liangxue Heying Formula on vascular inflammatory injury in a rat model of thromboangiitis obliterans via JAK2/STAT3 signaling pathway
Xia FENG ; Yu-Zhen WANG ; Yan-Dan ZHU ; Cheng ZHAO ; Ji LI ; Ye-Min CAO
Chinese Traditional Patent Medicine 2024;46(9):2915-2922
AIM To study the effects of Liangxue Heying Formula on vascular inflammatory injury in a rat model of thromboangiitis obliterans(TAO).METHODS The rats were randomly divided into the sham operation group,the model group and the low,medium and high dose Liangxue Heying Formula groups(2.25,4.5,9 g/kg).With the rat TAO model successfully established by injection of 0.1 mL sodium laurate(10 mg/mL)into the femoral artery of hind limbs,corresponding doses of drugs by gavage were administered upon the rats.Subsequently,the rats had their morphological changes of the affected limbs observed and assessed;their changes of blood flow in hind limbs scanned by laser Doppler flowmetry;their plasma levels of TNF-α,IL-6,ICAM-1 and VCAM-1 detected by ELISA;their histopathological changes of femoral artery and vein observed by HE staining;and their protein expressions of TNF-α,IL-6,JAK2,p-JAK2,STAT3,p-STAT3,ICAM-1 and VCAM-1 in femoral artery detected by Western blot.RESULTS Compared with the sham operation group,the model group displayed increased morphological score of the affected limb(P<0.01);decreased blood perfusion ratio of the affected side/healthy side(P<0.01);increased plasma levels of TNF-α,IL-6,ICAM-1 and VCAM-1(P<0.01);more existence of thrombotic infiltration containing a larger number of inflammatory cells in femoral artery and femoral vein tissue,and increased protein expressions of TNF-α,IL-6,p-JAK2,p-STAT3,ICAM-1 and VCAM-1 in femoral artery(P<0.01).Compared with the model group,the medium and high dose Liangxue Heying Formula groups demonstrated decreased morphological score of the affected limb(P<0.01);increased blood perfusion ratio of the affected side/healthy side(P<0.01);reduced infiltration of thrombus and inflammatory cells in femoral artery and femoral vein tissue,and decreased protein expressions of IL-6 and p-STAT3 in femoral artery tissue(P<0.01).All Liangxue Heying Formula groups shared decreased plasma levels of TNF-α,IL-6,ICAM-1 and VCAM-1(P<0.05,P<0.01);and reduced protein expressions of TNF-α,ICAM-1,VCAM-1 and p-JAK2 in femoral artery(P<0.01).CONCLUSION Liangxue Heying Formula can improve the systemic inflammatory state of TAO rats by inhibiting the activation of endothelial cells and reducing vascular inflammatory injury possibly due to the mechanism associated with the regulation of the JAK2/STAT3 signaling pathway.
6.Construction and implementation of a bed resource allocation management model based on lean man-agement principles
Dan HU ; Yongmei JIN ; Shuangshuang LI ; Hanchen NI ; Lingli XU ; Zhu JIN ; Baoqing YU
Modern Hospital 2024;24(10):1557-1559
Objective To construct a rational and efficient bed resource allocation management model to reduce pre-hos-pital waiting times,ensure patient safety,and improve satisfaction.Methods Based on lean management principles,a bed re-source allocation management model was developed and continuously optimized.The study compared bed turnover rates and effi-ciency indices,as well as preoperative waiting times for surgical patients,average length of stay,patient satisfaction,and anxiety incidence before and after the implementation of the lean model to evaluate its effectiveness.Results After implementing the lean bed resource allocation model,the bed efficiency index increased by 14.29%,and bed turnover rates improved by 3.34%.The average preoperative waiting time for surgical patients decreased by 100%,and the average length of stay reduced by 87.71%.Patient satisfaction increased by 2.4%,while anxiety incidence dropped by 28.1%.Conclusion The implementa-tion of a lean bed resource allocation model can enhance hospital bed efficiency,shorten preoperative waiting times for surgical patients,reduce average length of stay,and improve patient satisfaction.
7.Analysis of risk factors for clinical use of artificial intelligence-aided medical detection devices
Xiao-Yan ZHANG ; Yu-Tian LIU ; Tong-Cai WANG ; Dan-Dan ZHU ; Yue-Fei LI
Chinese Medical Equipment Journal 2024;45(11):77-82
The common risks of artificial intelligence-aided medical detection devices during the clinical application were analyzed.Some measures were put forward such as improving the design of the devices,ensuring data security and enhancing social and legal supervision,and references were provided for efficiently integrating clinical and data resources and achieving safety during the clinical application of medical devices.[Chinese Medical Equipment Journal,2024,45(11):77-82]
8.Association of nitric oxide/endothelin-1 ratio and low-density lipoprotein/apolipoprotein B ratio with early neuro-logical deterioration after acute ischemic stroke
Hong YU ; Dan LIU ; Lungang ZHU
Journal of Apoplexy and Nervous Diseases 2024;41(6):539-543
Objective To investigate the association of nitric oxide(NO)/endothelin-1(ET-1)ratio and low-density lipoprotein(LDL)/apolipoprotein B(ApoB)ratio with early neurological deterioration(END)after acute ischemic stroke(AIS).Methods A retrospective analysis was performed for the clinical data of 108 AIS patients who were admit-ted to Mianyang Hospital Affiliated to University of Electronic Science and Technology School of Medicine&Mianyang Central Hospital from March 2021 to March 2023,and the incidence rate of END within 24 hours after disease onset was analyzed.Laboratory data were collected to calculate NO/ET-1 ratio and LDL/ApoB ratio.A binary logistic regression analysis was used to analyze the influencing factors for END after AIS,and the receiver operating characteristic(ROC)curve was used to investigate the value of NO/ET-1 ratio and LDL/ApoB ratio in identifying END after AIS.Results END was observed in 23 patients,and the END group had significantly lower NO/ET-1 ratio and LDL/ApoB ratio than the non-END group(P<0.05).High NHISS score on admission and diabetes were risk factors for END after AIS(P<0.05),while NO/ET-1 ratio and LDL/ApoB ratio were protective factors(P<0.05).NO/ET-1 ratio and LDL/ApoB ratio had and area under the ROC curve(AUC)of 0.737 and 0.753,respectively,in predicting END after AIS,and NO/ET-1 ratio com-bined with LDL/ApoB ratio had an AUC of 0.900 in predicting END after AIS,suggesting that NO/ET-1 ratio combined with LDL/ApoB ratio had a significantly higher AUC than NO/ET-1 ratio or LDL/ApoB ratio alone(P<0.05).Conclusion The reductions in NO/ET-1 ratio and LDL/ApoB ratio in AIS patients are associated with the onset of END,and the combination of NO/ET-1 ratio and LDL/ApoB ratio has a higher value in predicting END after AIS.
9.Current status of health economic evaluation on the effectiveness of influ-enza vaccination
Dan-Ni ZHU ; Yao-Gang WANG ; Xin-Yu ZHANG
Chinese Journal of Infection Control 2024;23(10):1319-1325
Influenza is an acute respiratory infectious disease caused by influenza virus,which poses a serious risk to human health.People are generally susceptible to influenza virus.There is an international consensus that influ-enza vaccination is the most effective way to prevent and control influenza.In China,influenza vaccination is a non-immunization programme vaccine that is vaccinated voluntarily and at one's own expense.In some regions,immuni-zation policies are implemented for priority groups.In recent years,a number of health economic evaluations on in-fluenza vaccination have been conducted both at home and abroad,especially for key and high-risk populations such as pregnant women,children,elderly people aged ≥60 years old,people suffering from one or more chronic disea-ses,and health care workers.This paper analyzed the current status of researches on health economic evaluation of influenza vaccination through collating relevant literatures published at home and abroad in recent years,so as to provide a scientific basis for the formulation of influenza vaccination strategies in China.
10.Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients (version 2024)
Yao LU ; Yang LI ; Leiying ZHANG ; Hao TANG ; Huidan JING ; Yaoli WANG ; Xiangzhi JIA ; Li BA ; Maohong BIAN ; Dan CAI ; Hui CAI ; Xiaohong CAI ; Zhanshan ZHA ; Bingyu CHEN ; Daqing CHEN ; Feng CHEN ; Guoan CHEN ; Haiming CHEN ; Jing CHEN ; Min CHEN ; Qing CHEN ; Shu CHEN ; Xi CHEN ; Jinfeng CHENG ; Xiaoling CHU ; Hongwang CUI ; Xin CUI ; Zhen DA ; Ying DAI ; Surong DENG ; Weiqun DONG ; Weimin FAN ; Ke FENG ; Danhui FU ; Yongshui FU ; Qi FU ; Xuemei FU ; Jia GAN ; Xinyu GAN ; Wei GAO ; Huaizheng GONG ; Rong GUI ; Geng GUO ; Ning HAN ; Yiwen HAO ; Wubing HE ; Qiang HONG ; Ruiqin HOU ; Wei HOU ; Jie HU ; Peiyang HU ; Xi HU ; Xiaoyu HU ; Guangbin HUANG ; Jie HUANG ; Xiangyan HUANG ; Yuanshuai HUANG ; Shouyong HUN ; Xuebing JIANG ; Ping JIN ; Dong LAI ; Aiping LE ; Hongmei LI ; Bijuan LI ; Cuiying LI ; Daihong LI ; Haihong LI ; He LI ; Hui LI ; Jianping LI ; Ning LI ; Xiying LI ; Xiangmin LI ; Xiaofei LI ; Xiaojuan LI ; Zhiqiang LI ; Zhongjun LI ; Zunyan LI ; Huaqin LIANG ; Xiaohua LIANG ; Dongfa LIAO ; Qun LIAO ; Yan LIAO ; Jiajin LIN ; Chunxia LIU ; Fenghua LIU ; Peixian LIU ; Tiemei LIU ; Xiaoxin LIU ; Zhiwei LIU ; Zhongdi LIU ; Hua LU ; Jianfeng LUAN ; Jianjun LUO ; Qun LUO ; Dingfeng LYU ; Qi LYU ; Xianping LYU ; Aijun MA ; Liqiang MA ; Shuxuan MA ; Xainjun MA ; Xiaogang MA ; Xiaoli MA ; Guoqing MAO ; Shijie MU ; Shaolin NIE ; Shujuan OUYANG ; Xilin OUYANG ; Chunqiu PAN ; Jian PAN ; Xiaohua PAN ; Lei PENG ; Tao PENG ; Baohua QIAN ; Shu QIAO ; Li QIN ; Ying REN ; Zhaoqi REN ; Ruiming RONG ; Changshan SU ; Mingwei SUN ; Wenwu SUN ; Zhenwei SUN ; Haiping TANG ; Xiaofeng TANG ; Changjiu TANG ; Cuihua TAO ; Zhibin TIAN ; Juan WANG ; Baoyan WANG ; Chunyan WANG ; Gefei WANG ; Haiyan WANG ; Hongjie WANG ; Peng WANG ; Pengli WANG ; Qiushi WANG ; Xiaoning WANG ; Xinhua WANG ; Xuefeng WANG ; Yong WANG ; Yongjun WANG ; Yuanjie WANG ; Zhihua WANG ; Shaojun WEI ; Yaming WEI ; Jianbo WEN ; Jun WEN ; Jiang WU ; Jufeng WU ; Aijun XIA ; Fei XIA ; Rong XIA ; Jue XIE ; Yanchao XING ; Yan XIONG ; Feng XU ; Yongzhu XU ; Yongan XU ; Yonghe YAN ; Beizhan YAN ; Jiang YANG ; Jiangcun YANG ; Jun YANG ; Xinwen YANG ; Yongyi YANG ; Chunyan YAO ; Mingliang YE ; Changlin YIN ; Ming YIN ; Wen YIN ; Lianling YU ; Shuhong YU ; Zebo YU ; Yigang YU ; Anyong YU ; Hong YUAN ; Yi YUAN ; Chan ZHANG ; Jinjun ZHANG ; Jun ZHANG ; Kai ZHANG ; Leibing ZHANG ; Quan ZHANG ; Rongjiang ZHANG ; Sanming ZHANG ; Shengji ZHANG ; Shuo ZHANG ; Wei ZHANG ; Weidong ZHANG ; Xi ZHANG ; Xingwen ZHANG ; Guixi ZHANG ; Xiaojun ZHANG ; Guoqing ZHAO ; Jianpeng ZHAO ; Shuming ZHAO ; Beibei ZHENG ; Shangen ZHENG ; Huayou ZHOU ; Jicheng ZHOU ; Lihong ZHOU ; Mou ZHOU ; Xiaoyu ZHOU ; Xuelian ZHOU ; Yuan ZHOU ; Zheng ZHOU ; Zuhuang ZHOU ; Haiyan ZHU ; Peiyuan ZHU ; Changju ZHU ; Lili ZHU ; Zhengguo WANG ; Jianxin JIANG ; Deqing WANG ; Jiongcai LAN ; Quanli WANG ; Yang YU ; Lianyang ZHANG ; Aiqing WEN
Chinese Journal of Trauma 2024;40(10):865-881
Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

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