Alzheimer’s disease (AD) is a prevalent neurodegenerative condition characterized by progressive cognitive decline and memory loss. As the incidence of AD continues to rise annually, researchers have shown keen interest in the active components found in natural plants and their neuroprotective effects against AD. Quercetin, a flavonol widely present in fruits and vegetables, has multiple biological effects including anticancer, anti-inflammatory, and antioxidant. Oxidative stress plays a central role in the pathogenesis of AD, and the antioxidant properties of quercetin are essential for its neuroprotective function. Quercetin can modulate multiple signaling pathways related to AD, such as Nrf2-ARE, JNK, p38 MAPK, PON2, PI3K/Akt, and PKC, all of which are closely related to oxidative stress. Furthermore, quercetin is capable of inhibiting the aggregation of β‑amyloid protein (Aβ) and the phosphorylation of tau protein, as well as the activity of β‑secretase 1 and acetylcholinesterase, thus slowing down the progression of the disease.The review also provides insights into the pharmacokinetic properties of quercetin, including its absorption, metabolism, and excretion, as well as its bioavailability challenges and clinical applications. To improve the bioavailability and enhance the targeting of quercetin, the potential of quercetin nanomedicine delivery systems in the treatment of AD is also discussed. In summary, the multifaceted mechanisms of quercetin against AD provide a new perspective for drug development. However, translating these findings into clinical practice requires overcoming current limitations and ongoing research. In this way, its therapeutic potential in the treatment of AD can be fully utilized.

Objective To analyze the medication rules of Chinese herbal concentrated-granule for the treatment of hypertension nationwide using data mining and knowledge graph methods,thus to provide evidence for expanding its application in treating hypertension.Methods From January 2022 to March 2023,Chinese herbal concentrated-granule prescriptions for hypertension prescribed by traditional Chinese medicine experts nationwide were collected.Microsoft Excel was used to analyze the frequency,properties and flavors,meridian tropism,and efficacy categories of the medicinals.Hierarchical clustering was applied for cluster analysis,and the Neo4j graph database was utilized to construct an information knowledge graph illustrating the relationships between regions and medicinals.Results A total of 2 600 Chinese herbal concentrated-granule prescriptions were included,involving 370 medicinals.The top six frequently-used medicinals were Poria(Fuling),Glycyrrhizae Radix et Rhizoma(Gancao),Atractylodis Macrocephalae Rhizoma(Baizhu),Citri Reticulatae Pericarpium(Chenpi),Paeoniae Radix Alba(Baishao),and Angelicae Sinensis Radix(Danggui).The properties of the medicinals were mainly warm and mild,and their flavors were usually sweet,pungent,and bitter.The medicinals frequently have the meridian tropism of the spleen,lung,and liver meridians.Hierarchical clustering yielded seven clusters.The information knowledge graph of region-medicinals relationships revealed that medicinals used in five or more regions were Baishao,Baizhu,Chenpi,Pinelliae Rhizoma(Banxia),Fuling,Gastrodiae Rhizoma(Tianma),Bupleuri Radix(Chaihu),Chuanxiong Rhizoma(Chuanxiong),Salviae Miltiorrhizae Radix et Rhizoma(Danshen),Danggui,Gancao,and Astragali Radix(Huangqi).Conclusion Chinese herbal concentrated-granule for hypertension usually consist of tonifying medicinals,with sweet and warm properties,and having the meridian tropism of the spleen meridian.And the medicinals composed of the prescriptions often have the actions of calming the liver and suppressing yang,strengthening the spleen and removing dampness,and nourishing the liver and kidney.

Objective To establish a rat model of acclimatization to motion sickness(MS)induced by rotational stimulation.Methods To determine the stimulation conditions of MS,SD rats were divided into a static control group(SCG)and a single rotation stimulation group(SRG)before being subjected to the motion sickness index(MSI)measurement,open-field experiment and Morris water maze experiment after rotational stimulation to verify the feasibility of MS being induced in rats.Morris water maze experiments were performed to find out whether rotational stimulation could be used to induce MS in rats.During experiments on acclimatization,the SD rats were divided into the control group(Ctrl),one day of rotational stimulation group(Day1),three days of continuous rotational stimulation group(Day3),and seven days of continuous rotational stimulation group(Day7)before the changes in the MSI and behavior of these rats were recorded so as to explore the relationship between continuous stimulation and MS acclimatization in rats.Results After rotational stimulation,the rats showed a significant increase in the number of fecal pellets(P<0.0001)and in the MSI(P<0.0001)compared with the SCG.In the open field experiment,the rats showed a significant decrease in the spontaneous activity time(AT)(P<0.0001),total spontaneous activity distance(TD)(P<0.001)and distance moved by the center point per second(DMCPS)(P<0.001).The time taken to climb onto the platform(latency to find the platform,LP)(P<0.0001)and the total distance to the platform(distance to the platform,DP)(P<0.001)were significantly increased during the Morris water maze experiment.Acclimatization experiments revealed a significant increase in MSI and in the number of fecal pellets in the Day1 and Day3 groups of rotational stimulation compared to the Ctrl group(P<0.0001).AT(P<0.01),TD(P<0.05)and DMCPS(P<0.01)were significantly decreased,while LP and DP were significantly increased(P<0.0001),but there was no statistically significant difference in indices compared with the Day7 group(P>0.05).Conclusion Sinusoidal stimulation can induce MS in rats,and twice-a-day,continuous rotational stimulation for seven days can lead to acclimatization.The rat MS model can be assessed via behavioral experiments.

Objective To understand the current situation of reprocessing reusable sterilized items in the central sterile supply departments(CSSD)of hospitals and provide a scientific basis for further standardized management.Methods Using the convenience sampling method,a self-designed questionnaire on the current situation of reprocessing of reusable disinfection items in CSSDs was used to conduct a survey in 31 provinces(autonomous regions and municipalities)from June 11th to 23rd,2024.The questionnaire covered 2 aspects,including the basic situation of the hospital and the reprocessing of disinfection items.Results A total of 1 835 questionnaires were distributed,and 1 603 valid questionnaires were retrieved.Regarding the use of reusable disinfection items,with the most frequently used items being humidification bottles,tourniquets,breathing bags and their accessories,and ventilator tubing systems etc.Among them,1 558 hospitals(97.19％)established standardized disposal procedures,and 996 hospitals(62.13％)assigned dedica-ted personnel to be responsible.In terms of the reprocessing procedures of reusable disinfection items,all 1 603 hospitals carried out drying process for the items;the main packaging method was plastic self-sealing bags(59.95％),and 541 hospitals(33.75％)sterilized the packaging materials.Additionally,935 hospitals(58.33％)used oil-free air compressors;among them,51 hospitals(58.62％)installed activated carbon filters at the end of the compressors.Conclusion The current situation of reprocessing reusable sterilized items in CSSDs of nationwide hospitals needs improvement.It is recommended to strengthen the training of professional disinfection knowledge,unify the sterilization standards for plastic self-sealing bags,develop a storage management system,and adopt a medical air compressor system without oil and water to reduce the risk of hospital infections.

Objective To study the epidemiological characteristics of special pathogenic infection in Wenchang area following the super typhoon"Yagi"disaster,and provide basis for the diagnosis,treatment,prevention and control of infectious diseases in disaster-affected areas.Methods Clinical characteristics and pathogenic data of 7 groups of patients infected with 9 species of zoonotic pathogens and opportunistic pathogens were analyzed retrospectively.The 7 groups included:pre-typhoon landfall group(August 6 to September 5,2024),post-typhoon landfall group(September 6 to October 5,2024),and groups in the past years of the same period(A2023,B2022,C2021,D2020,E2019,September 6 to October 5 of each year in 2019-2023).Epidemiological characteristics of patients as well as distribution and resistance of pathogens were compared and analyzed.Results In post-typhoon landfall group,26 patients were infected.The overall infection rate of the post-typhoon landfall group was higher than all groups except B2022 group(all P＜0.05).The infected cases mainly distributed in coastal areas.The main route of infection was outside the hospital(88.5％).Male accounted for 80.8％,agricultural workers accounted for 53.9％,and 69.2％of the cases occurred within 10 days after the typhoon.The major infection sites were multiple site co-infection,bloodstream infection,and soft tissue infection.The main pathogens maintained high sensitivity to commonly used antimicrobial agents.The accuracy of clinical initial empirical antimicrobial use was relatively low(45.5％in post-typhoon landfall group vs 62.8％in the groups of the same period in the past).The clinical cure rate decreased to 76.9％,and mortality increased to 7.7％.The mortality of patients infected with Burkholderia pseudomallei and kidney infected with Leptospira were 25.0％and 50.0％,respectively.Conclusion After ty-phoon disaster,special pathogen infection significantly increases and the prognosis is poor.It is recommended to emphasize blood culture and molecular biology testing to facilitate early diagnosis and precise treatment,optimize prevention and control measures,and enhance the accuracy of clinical empirical medication.

OBJECTIVE: Circadian rhythm disruption (CRD) is a risk factor that correlates with poor prognosis across multiple tumor types, including hepatocellular carcinoma (HCC). However, its mechanism remains unclear. This study aimed to define HCC subtypes based on CRD and explore their individual heterogeneity. METHODS: To quantify CRD, the HCC CRD score (HCCcrds) was developed. Using machine learning algorithms, we identified CRD module genes and defined CRD-related HCC subtypes in The Cancer Genome Atlas liver HCC cohort (n = 369), and the robustness of this method was validated. Furthermore, we used bioinformatics tools to investigate the cellular heterogeneity across these CRD subtypes. RESULTS: We defined three distinct HCC subtypes that exhibit significant heterogeneity in prognosis. The CRD-related subtype with high HCCcrds was significantly correlated with worse prognosis, higher pathological grade, and advanced clinical stages, while the CRD-related subtype with low HCCcrds had better clinical outcomes. We also identified novel biomarkers for each subtype, such as nicotinamide n-methyltransferase and myristoylated alanine-rich protein kinase C substrate-like 1. CONCLUSION We classify the HCC patients into three distinct groups based on circadian rhythm and identify their specific biomarkers. Within these groups greater HCCcrds was associated with worse prognosis. This approach has the potential to improve prediction of an individual's prognosis, guide precision treatments, and assist clinical decision making for HCC patients. Please cite this article as: Li XJ, Chang L, Mi Y, Zhang G, Zhu SS, Zhang YX, et al. Integrated-omics analysis defines subtypes of hepatocellular carcinoma based on circadian rhythm. J Integr Med. 2025; 23(4): 445-456.
Humans ; Carcinoma, Hepatocellular/pathology* ; Liver Neoplasms/pathology* ; Circadian Rhythm/genetics* ; Prognosis ; Male ; Female ; Biomarkers, Tumor/genetics* ; Middle Aged ; Machine Learning ; Computational Biology

AIM:To investigate the role of SET and MYND domain-containing protein 3(SMYD3)-mediated histone H3 lysine 4 trimethylation(H3K4me3)dysregulation in pulmonary vascular remodeling in a rat model of pulmo-nary arterial hypertension associated with atrial septal defect(PAH-ASD).METHODS:The PAH-ASD rat model was created using transseptal puncture and radiofrequency ablation techniques.The rats were randomly assigned to 5 groups:normal,sham,PAH-ASD,PAH-ASD+vehicle(Veh),and PAH-ASD+BCI-121(SMYD3 inhibitor).Four weeks after modeling,lung tissues and pulmonary vessels were harvested for subsequent analysis.Western blot analysis was conducted to evaluate the protein levels of SMYD3,H3K4me3,transforming growth faction-β1(TGF-β1),and collagen type Ⅲ(Col Ⅲ).The mRNA expression of TGF-β1 was quantified using RT-qPCR.Histological assessment of pulmonary vascu-lar fibrosis,vascular wall thickness and smooth muscle proliferation was executed through Masson's trichrome and HE staining.Co-immunoprecipitation(Co-IP)assay was performed to investigate the interactions among SMYD3,H3K4me3,and TGF-β1.Hemodynamic parameters,including mean pulmonary artery pressure(mPAP),were quantified using a computerized physiological signal acquisition system.RESULTS:The Western blot analysis indicated a significant in-crease in the protein levels of SMYD3,TGF-β1,Col Ⅲ,and H3K4me3 in the PAH-ASD group compared with the sham group(P<0.05).RT-qPCR corroborated the elevation of TGF-β1 mRNA expression in the PAH-ASD group(P<0.05).Furthermore,Masson's trichrome and HE staining techniques revealed more pronounced pulmonary vascular fibrosis,an augmented vascular wall area,and an elevated vascular area index within the PAH-ASD group(P<0.05).Additionally,the right ventricular hypertrophy index(RVHI)and mPAP were significantly elevated in the PAH-ASD group(P<0.05).The administration of BCI-121 resulted in a significant reduction of SMYD3,TGF-β1,Col Ⅲ,and H3K4me3 levels(P<0.05),while also mitigating pulmonary vascular fibrosis,RVHI,mPAP,pulmonary vascular area,and area index(P<0.05).Co-IP confirmed direct interactions among SMYD3,H3K4me3,and TGF-β1.CONCLUSION:Histone methyl-transferase SMYD3-mediated histone H3K4me3 modification plays a role in the pulmonary vascular remodeling of PAH-ASD model rats.The underlying mechanism may involve the regulation of pulmonary vascular proliferation and fibrosis me-diated by the overexpression of TGF-β1 and Col Ⅲ.

Chronic kidney disease(CKD)is a chronic disease characterized by renal structural damage and dysfunction.At present,there is still a lack of effective therapeutic drugs and prevention and treatment methods for CKD in clinical practice.More and more studies have shown that necroptosis,as a new type of programmed cell death,plays a vital role in the onset and progression of CKD.Targeting key molecules in the necroptosis pathway,such as RIPK1,RIPK3 and MLKL,the development of small molecule inhibitors has become an emerging strategy for the treatment of CKD,and has shown significant potential to pro-tect the kidneys and alleviate renal fibrosis in a variety of in vitro and in vivo models.Therefore,this article summarizes the re-search progress of the mechanism of necroptosis in recent years,and focuses on the potential role of necroptosis in the pathogene-sis of CKD and the therapeutic potential of targeting this path-way,providing a new perspective and research direction for the prevention and treatment of CKD in the future.

N⁶-methyladenosine (m⁶A) modification plays a critical role in cell cycle regulation, while the mechanism of m⁶A in regulating mitosis remains underexplored. Here, we found that the total m⁶A modification level in cells increased during mitosis by the liquid chromatography-mass spectrometry/mass spectrometry and m⁶A dot blot assays. Silencing methyltransferase-like 3 (METTL3) or METTL14 results in delayed mitosis, abnormal spindle assembly, and chromosome segregation defects by the immunofluorescence. By analyzing transcriptome-wide m⁶A targets in HeLa cells, we identified polo-like kinase 1 (PLK1) as a key gene modified by m⁶A in regulating mitosis. Specifically, through immunoblotting and RNA pulldown, m⁶A modification inhibits PLK1 translation via YTH N⁶-methyladenosine RNA binding protein 1, thus mediating cell cycle homeostasis. Demethylation of PLK1 mRNA leads to significant mitotic abnormalities. These findings highlight the critical role of m⁶A in regulating mitosis and the potential of m⁶A as a therapeutic target in proliferative diseases such as cancer.
Humans ; Polo-Like Kinase 1 ; Cell Cycle Proteins/metabolism* ; Proto-Oncogene Proteins/metabolism* ; Protein Serine-Threonine Kinases/metabolism* ; Mitosis/physiology* ; HeLa Cells ; Adenosine/genetics* ; Methyltransferases/metabolism* ; RNA, Messenger/metabolism* ; RNA-Binding Proteins/metabolism*

BACKGROUND: Medical informatics accumulated vast amounts of data for clinical diagnosis and treatment. However, limited access to follow-up data and the difficulty in integrating data across diverse platforms continue to pose significant barriers to clinical research progress. In response, our research team has embarked on the development of a specialized clinical research database for cardiology, thereby establishing a comprehensive digital platform that facilitates both clinical decision-making and research endeavors. METHODS: The database incorporated actual clinical data from patients who received treatment at the Cardiovascular Medicine Department of Chinese PLA General Hospital from 2012 to 2021. It included comprehensive data on patients' basic information, medical history, non-invasive imaging studies, laboratory test results, as well as peri-procedural information related to interventional surgeries, extracted from the Hospital Information System. Additionally, an innovative artificial intelligence (AI)-powered interactive follow-up system had been developed, ensuring that nearly all myocardial infarction patients received at least one post-discharge follow-up, thereby achieving comprehensive data management throughout the entire care continuum for high-risk patients. RESULTS: This database integrates extensive cross-sectional and longitudinal patient data, with a focus on higher-risk acute coronary syndrome patients. It achieves the integration of structured and unstructured clinical data, while innovatively incorporating AI and automatic speech recognition technologies to enhance data integration and workflow efficiency. It creates a comprehensive patient view, thereby improving diagnostic and follow-up quality, and provides high-quality data to support clinical research. Despite limitations in unstructured data standardization and biological sample integrity, the database's development is accompanied by ongoing optimization efforts. CONCLUSION The cardiovascular specialty clinical database is a comprehensive digital archive integrating clinical treatment and research, which facilitates the digital and intelligent transformation of clinical diagnosis and treatment processes. It supports clinical decision-making and offers data support and potential research directions for the specialized management of cardiovascular diseases.