OBJECTIVE To investigate the improvement mechanism of hyperoside （HYP） on non-alcoholic fatty liver disease （NAFLD）. METHODS Male C57BL/6 mice were randomly divided into normal （NFD） group， model （HFD） group and HYP group， with 8 mice in each group. Except for NFD group， the mice in other groups were fed with HF60 high-fat diet to establish NAFLD model； HYP group was simultaneously given HYP 100 mg/kg intragastrically every day， for 16 consecutive weeks. The body weight and liver weight of mice in each group were recorded 16 h after the last medication； the histopathological changes and lipid accumulation in the liver were observed， and the contents of triglyceride （TAG） in liver tissue and serum contents of TAG， aspartate transaminase （AST） and alanine transaminase （ALT） were measured； LC-MS/MS method was adopted to detect lipid changes in the liver tissue of mice for lipidomics analysis， and protein expressions of lipid synthesis-associated proteins peroxisome proliferator-activated receptor α （PPARα） were also tested. Human hepatocellular carcinoma cell line HepG2 was divided into normal control group， model group， HYP low-concentration group （50 μmol/L）， HYP high-concentration group （100 μmol/L）， HYP low-concentration+GW6471 （PPARαinhibitor） group， and HYP high-concentration+GW6471 group. Except for normal control group， the remaining cells were induced with oleic acid and palmitic acid to establish a high-fat cell model. The accumulation of lipid droplets in each group of cells was observed， and the TAG content was detected. RESULTS Compared with HFD group， HYP group exhibited significant reductions in liver fat vacuoles， lipid accumulation， liver weight， and TAG content in liver tissue， as well as serum contents of ALT， AST and TAG （P＜0.05）. Additionally， the expression of PPARα protein in liver tissue was significantly increased （P＜0.05）， and the pathological morphological changes associated with NAFLD were alleviated. Lipidomic analysis revealed that HYP significantly reduced the levels of TAG， diacylglycerol and other lipids in the liver. Compared with model group， cellular lipid droplet accumulation and TAG content decreased significantly in HYP low- and high-concentration groups （P＜0.05）； GW6471 could significantly reverse the improvement effect of HYP on above indicators （P＜0.05）. CONCLUSIONS HYP can effectively ameliorate NAFLD induced by a high-fat diet in mice， and the mechanism may be related to the activation of PPARα to regulate hepatic lipid synthesis.

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.

To promote the development of extracellular vesicles of herbal medicine especially the establishment of standardization, led by the National Expert Committee on Research and Application of Chinese Herbal Vesicles, research experts in the field of herbal medicine and extracellular vesicles were invited nationwide with the support of the Expert Committee on Research and Application of Chinese Herbal Vesicles, Professional Committee on Extracellular Vesicle Research and Application, Chinese Society of Research Hospitals and the Guangdong Engineering Research Center of Chinese Herbal Vesicles. Based on the collation of relevant literature, we have adopted the Delphi method, the consensus meeting method combined with the nominal group method to form a discussion draft of "Consensus statement on research and application of Chinese herbal medicine derived extracellular vesicles-like particles (2023)". The first draft was discussed in online and offline meetings on October 12, 14, November 2, 2022 and April and May 2023 on the current status of research, nomenclature, isolation methods, quality standards and research applications of extracellular vesicles of Chinese herbal medicines, and 13 consensus opinions were finally formed. At the Third Academic Conference on Research and Application of Chinese Herbal Vesicles, held on May 26, 2023, Kewei Zhao, convenor of the consensus, presented and read the consensus to the experts of the Expert Committee on Research and Application of Chinese Herbal Vesicles. The consensus highlights the characteristics and advantages of Chinese medicine, inherits the essence, and keeps the righteousness and innovation, aiming to provide a reference for colleagues engaged in research and application of Chinese herbal vesicles at home and abroad, decode the mystery behind Chinese herbal vesicles together, establish a safe, effective and controllable accurate Chinese herbal vesicle prevention and treatment system, and build a bridge for Chinese medicine to the world.

Under the backdrop of smart health management technology development, this article reviews research advances in smart monitoring, assessment and intervention technologies for older people with mild cognitive impairment, including the types, typical applications and results of monitoring, assessment and intervention technologies.In addition, from the perspective of community-dwelling older adults' cognitive health management, a model for innovative management of community-dwelling older adults' cognitive function taking advantage of smart health management technologies is proposed, aiming to enhance the acceptance of smart health technologies among older people with cognitive impairment and to provide policy advice on developing friendly communities for older people with cognitive impairment.

OBJECTIVE To study the effects of bergapten in the treatment of liver fibrosis and its mechanism based on serum metabolomics. METHODS Forty mice were divided into normal control group （0.5% carboxymethyl cellulose sodium solution）， model group （0.5% carboxymethyl cellulose sodium solution）， and BP low-dose and high-dose groups （50， 100 mg/kg）， with 10 mice in each group. Except for the normal control group， the other three groups were all treated with carbon tetrachloride to induce liver fibrosis model； they were given relevant medicine/solution intragastrically， once a day， for consecutive 8 weeks. After the last medication， the levels of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） in serum were detected， and liver pathological changes were observed； the expressions of α-smooth muscle actin （α-SMA） and Collagen Ⅰ were detected in liver tissue； the serum of the mice was collected for metabolomics analysis. RESULTS Compared with the model group， serum levels of ALT and AST and protein expressions of α-SMA and Collagen Ⅰ in liver tissue were decreased significantly in BP high-dose and low-dose groups （P＜0.05）， while liver fibrosis was improved significantly. Meanwhile， metabolomics analyses showed that there were a total of 175 serum differential metabolites in the BP high-dose group and model group， of which 18 substances were upregulated and 157 substances were downregulated； the main metabolic pathways involved in bergapten intervention were pyrimidine metabolism， butanoate metabolism， fatty acid synthesis， tyrosine metabolism， β-alanine metabolism， nicotinic acid and nicotinamide metabolism， glutathione metabolism， etc. CONCLUSIONS BP is effective in the treatment of liver fibrosis by regulating pyrimidine metabolism， butanoate metabolism， glutathione metabolism and so on in rats with liver fibrosis.

Objective : To investigate the drug resistance and pathogenicity of six clinical isolates of Klebsiella pneu- moniae (Kp) ，and to provide a basis for prevention and treatment of Kp infection． Methods : The six strains from different hospitals were isolated ，cultured ，and identified by species-specific gene khe． Their whole genome se- quences (WGS) were obtained using next-generation sequencing technology (NGS) ．Based on the WGS，the cap- sular serotypes，sequence types (ST) and drug-resistance genes of six strains were identified．The capsular sero- type genes and virulence genes were validated or identified using PCR. Broth microdilution tests were conducted to validate their drug susceptibility，and mice were challenged with Kp aerosols by MicroSprayer aerosolizer to evaluate their pathogenicity. Results : The six strains were all serotype K2 but belonged to four ST types ( ST14 ，ST65， ST700，and ST86) ，and collectively carried six virulence genes and 23 drug-resistance genes．All the six strains were resistant to ampicillin，but only one strain was multidrug-resistant．Four strains exhibited high mucoid charac- teristics．Five strains could cause mortality in mice，which were preliminary identified as high virulence strains. Conclusion For the six Kp clinical isolates from different sources，only one strain named NY 13294 is both multi- drug-resistant and highly virulent，and other four highly virulent strains are resistant to one or two types of antibiot- ics.

Objective To investigate the epidemiological characteristics of local visceral leishmaniasis in Beijing Municipality from 2021 to 2023, so as to provide insights into formulation of the visceral leishmaniasis control strategy. Methods Epidemiological data of visceral leishmaniasis cases reported in Beijing Municipality from 2021 to 2023 were collected from the National Health Informatization Disease Prevention and Control Information System, and the epidemiological characteristics of local visceral leishmaniasis cases were analyzed using a descriptive epidemiological method. In November 2021 and 2023, 50 to 100 permanent residents were voluntarily selected within a 100 meter radius of sites where patients lived or acquired Leishmania infections, and venous blood was sampled for anti-Leishmania antibody testing. Venous blood was sampled from dogs for anti-Leishmania antibody testing in natural villages where patients lived or acquired Leishmania infections, or in districts where Leishmania infected dogs were reported. In addition, sandflies were captured with CO₂ mosquito traps and fine mesh nets in natural villages where patients lived or acquired Leishmania infections from May to September, 2021 and 2023, for sandfly species identification. Results A total of 4 local visceral leishmaniasis cases were reported in Beijing Municipality from 2021 to 2023, with ages of 2 to 77 years, and acquiring Leishmania infections in Mentougou District (2 cases), Changping District (1 case), and Yanqing District (1 case). The anti-Leishmania antibody testing was all negative in 73 human blood samples and the sero-prevalence of anti-Leishmania antibody was 25.00% in 36 venous blood samples from domestic dogs in 2021, with a total of 4 520 Phlebotomus chinensis captured. The sero-prevalence of anti-Leishmania antibody was 0.51% in 198 human blood samples and 13.58% in 243 venous blood samples from domestic dogs in 2023, with 16.10%, 25.00%, 17.78% and 3.13% sero-prevalence in dogs sampled from Mentougou District, Changping District, Yanqing District and Haidian District, respectively (P = 0.011), while a total of 1 712 Ph. chinensis were captured, including 1 421 female sandflies (86.54%). Conclusions The prevalence of local visceral leishmaniasis was low in Beijing Municipality from 2021 to 2023; however, there is a risk of further spread in the epidemic foci. Intensified visceral leishmaniasis surveillance and control is recommended.

Purpose To explore the clinicopathological features,diagnosis and differential diagnosis of large B-cell lym-phoma with IRF4 rearrangement(LBCL-IRF4r).Methods Clinical data of 8 cases of LBCL-IRF4r were collect,hematoxy-lin-eosin and immunohistochemical of EnVision two-step stains,in situ hybridization and FISH was used to study the histology,immunotypes and molecular genetic characteristics.The rele-vant literatures were reviewed.Results Among 8 cases of LBCL-IRF4r,the male to female ratio was 1.67:1,with age range 10-53 years(mean 25.8 years).Five cases occurred in tonsils,2 cases in nasopharynx and 1 cases in inguinal lymph node.Microscopically,the tumors presented with a purely follic-ular,purely diffuse or a combined follicular and diffuse architec-ture.The tumor cells were typical centroblasts and less frequent-ly medium-sized blastic cells with smaller nucleoli,apoptosis and nuclear fragmentation were easily seen.Immunophenotypi-cally,the tumor cells of the eight cases of LBCL-IRF4r diffuse strongly expressed CD20(8/8),PAX5(2/2),CD79a(3/3),BCL6(8/8)and MUM-1(8/8),mostly expressed CD10(7/8),partially expressed BCL2(5/8)and CD5(4/8),and did not express Cyclin D1,CD23 and CD30.The percentage of Ki67 index ranged from 70％to 95％.EBER in situ hybridiza-tion was negative in all cases.IRF4 rearrangements were detec-ted in all cases(8/8).BCL6 rearrangements were detected in one case(1/2).MYC(0/4)and BCL2(0/3)rearrangements were not detected in all cases.Conclusion LBCL-IRF4r is more common in children and adolescents with characteristic IG::IRF4 rearrangement and a good prognosis,which needs to be differentiated from other types of large B-cell lymphoma.

Objective:To investigate the pollution levels and influencing factors of polybrominated diphenyl ethers (PBDEs) in household dust in five cities in northern China.Methods:Based on the "Chinese Indoor Environment and Health Surveillance" project carried out by the National Institute of Environmental Health, Chinese Center for Disease Control and Prevention in 2018-2019, during the warm season (April 2018 to September 2018) and the cold season (November 2018 to March 2019), Lanzhou in Northwest China, Shijiazhuang in North China, Panjin in Northeast China, Luoyang in Central China, and Qingdao in East China were selected as the research sites. A total of 87 families were recruited to study residences in real-life scenarios. At the same time, dust samples were collected to detect the concentration of PBDEs. The level of household environmental indicators was measured, and the residential building characteristics and family behavior habits were collected through questionnaires. A total of 142 valid dust samples and 140 valid questionnaires were obtained. The differences in PBDE concentrations across seasons, wind zones, residential building characteristics, and family habits were analyzed. The exploratory factor analysis was performed to investigate the possible sources of PBDEs, and multivariate linear regression was used to explore the factors influencing PBDEs in household dust.Results:The M ( Q1,Q3) of total PBDE concentrations in 142 household dust samples in five cities was 144.51 (106.61, 222.65) ng/g in the warm season and 145.10 (98.57, 180.65) ng/g in the cold season, respectively. There were seasonal differences in the concentration of ∑ 12PBDEs in Luoyang and Shijiazhuang ( P<0.01). The concentration of BDE-71 was highest among PBDE homologues, followed by BDE-66 and BDE-47. Three factors were extracted by exploratory factor analysis in the warm season, and the cumulative variance contribution rate was 67.90%. The multivariate linear regression showed that the house completion less than ten years [ β (95% CI): 0.186 (0.013, 0.359)], infrequent home cooking [ β (95% CI):-0.342 (-0.570, -0.114)], and increased residential PM 10 concentration [ β (95% CI): 0.001 (0.000, 0.002)] during the warm season, as well as the house far from driveway [ β (95% CI): 0.093 (0.013, 0.172)], house area less than 90 m 2 [ β (95% CI):-0.138 (-0.264, -0.013)], and lower residential xylene concentration [ β (95% CI):-0.006 (-0.011, -0.001)] during the cold season might be related to the elevated concentrations of ∑ 12PBDEs in household dust. Conclusion:The pollution of PBDEs in household dust in five northern cities is at a medium to high level. Years of house completion, frequency of cooking at home, residential PM 10 concentration, distance from house to driveway, house area, and residential xylene concentration may influence household PBDE concentrations.

AIM:To investigate the mechanism of chronic stress-induced myocardial injury in atherosclerotic(AS)mice.METHODS:Eight-week-old SPF-grade male ApoE-/-mice and C57BL/6J mice used in this study.The mice received dietary intervention for 10 weeks followed by pathological examination to test the successful AS modeling.After AS establishment,the mice were exposed to chronic unpredictable mild stress(CUMS)for 6 weeks and then divided into five groups:control,CUMS,AS-regular diet(AS-r)+CUMS,AS-high-fat diet(AS-h),and AS-h+CUMS.During CUMS,open-field test and sucrose preference test were performed on mice in all groups.Blood lipids were characterized using an automatic biochemical analyzer.Hematoxylin-eosin(HE)and oil red O staining were performed to evaluate pathological changes in the aortic root.Cardiac function was assessed using echocardiography.The serum concentration of myocardial injury markers and ATP content was detected by ELISA.Transmission electron microscopy was employed to observe the ul-trastructure of myocardial mitochondria.Myocardial mitochondrial oxygen consumption rate was determined using the Oxy-graph-2k high-resolution respiratory energy metabolism analyzer.Western blot was conducted to quantify the expression of B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),and cleaved caspase-3.RESULTS:compared with the Control group,the total distance traveled,the number of entries into the central area,and the sucrose preference rate were significantly decreased in all CUMS groups(P<0.05).All AS groups exhibited varying levels of lipid deposition and endo-thelial damage in the aortic root,along with a significant reduction in cardiac function(P<0.05)and varying degrees of myocardial injury(P<0.05).In the AS-h+CUMS and AS-r+CUMS groups,myocardial mitochondrial structure was signifi-cantly disrupted.ATP content was significantly reduced(P<0.05),and the rates of oxygen consumption associated with mitochondrial respiratory chain complex I,mitochondrial respiratory chain complexes I+II,and the maximum respiratory capacity of the electron transport system were all significantly decreased(P<0.05).Moreover,the protein levels of Bax and cleaved caspase-3 were significantly increased(P<0.05),while that of Bcl-2 protein was significantly decreased(P<0.05).CONCLUSION:Chronic stress triggers mitochondrial non-steady-state load by disrupting myocardial structure and energy metabolism in AS mice,promoting myocardial cell apoptosis and myocardial injury.