ObjectiveTo investigate the therapeutic effects of the Anemarrhenae Rhizoma water extract （AR） on Alzheimer's disease （AD） model rats and to explore its potential underlying mechanisms. MethodsMale rats were intraperitoneally injected with D-galactose （100 mg·kg^-1） for 42 days， and on day 14， 1 μL of β-amyloid （Aβ_25-35， 2 g·L^-1） solution was injected into the hippocampus. Rats were randomly divided into a model group， low-dose AR （0.6 g·kg^-1）， medium-dose AR （1.2 g·kg^-1）， high-dose AR （2.4 g·kg^-1）， and a positive control group （donepezil， 5 mg·kg^-1）. Healthy rats receiving only a hippocampal injection of 1 μL of sterile saline served as the sham-operated group. From day 21， rats in the treatment groups were administered the corresponding drugs by gavage once daily for 21 consecutive days， while the blank control and model groups received an equal volume of saline. Learning and memory abilities were assessed using the Morris water maze. Brain tissue damage was observed by hematoxylin and eosin （HE） staining， and neuronal apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick-end labeling （TUNEL） staining. Levels of interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， and interleukin-10 （IL-10） in brain tissues were measured by enzyme-linked immunosorbent assay （ELISA）. BV2 microglial cells were co-cultured with Aβ_25-35 （40 μmol·L^-1） for 2 h， and cell viability was determined by the CCK-8 assay to screen the optimal concentration of AR-containing serum （S-AR）. Cells were divided into blank control， Aβ_25-35， S-AR， EX527 ［silent information regulator 1 （SIRT1） inhibitor］， and S-AR+EX527 groups. Immunofluorescence staining was used to detect the expression of CD16， CD206， and high-mobility group box 1 （HMGB1）. Western blot analysis was performed to measure the protein expression of CD16， inducible nitric oxide synthase （iNOS）， CD206， arginase （Arg）， and proteins related to the SIRT1/HMGB1/nuclear factor-κB （NF-κB） signaling pathway. ResultsIn vivo experiments showed that， compared with the sham-operated group， the model group exhibited reduced platform crossings and time spent in the target quadrant （P<0.01）， prolonged escape latency， increased hippocampal neuronal apoptosis （P<0.01）， and obvious hippocampal damage. The expression levels of IL-6， TNF-α， IL-10， CD16， and iNOS in brain tissues were significantly elevated （P<0.01）， while CD206 and Arg protein expression showed an increasing trend without statistical significance. Compared with the model group， all AR-treated groups significantly increased platform crossings and target quadrant time （P<0.05， P<0.01）， alleviated hippocampal damage， reduced escape latency and neuronal apoptosis， downregulated the expression of TNF-α， IL-6， CD16， and iNOS （P<0.05， P<0.01）， and upregulated the expression of IL-10， CD206 and Arg （P<0.05， P<0.01）. In vitro experiments demonstrated that， compared with the blank control group， the Aβ_25-35 group showed increased fluorescence intensity of CD206， CD16， and HMGB1， as well as elevated protein expression of iNOS and CD16 （P<0.01）， while CD206 and Arg protein expression exhibited an increasing trend without statistical significance. After S-AR intervention， CD206 fluorescence intensity and the protein expression of Arg and CD206 were significantly increased （P<0.01）， whereas the fluorescence intensity of CD16 and HMGB1 and the protein expression of iNOS and CD16 were significantly decreased （P<0.01）. These effects were reversed by EX527 （P<0.05， P<0.01）. Furthermore， compared with the blank control group， the Aβ_25-35 group showed significantly increased cytoplasmic HMGB1 expression and p-p65/p65 ratio （P<0.01）， along with significantly decreased SIRT1 and nuclear HMGB1 expression （P<0.01）. In contrast， the S-AR group exhibited opposite trends compared with the Aβ_25-35 group， and the regulatory effects of S-AR on these proteins were reversed by EX527 （P<0.01）. ConclusionAR exerts neuroprotective effects in AD model rats by regulating microglial polarization and alleviating neuroinflammation， potentially through modulation of the SIRT1/HMGB1/NF-κB signaling pathway.

Aging has emerged as a cutting edge and hotspot in global life science field， with anti-aging and geriatric disease prevention and treatment becoming critical issues urgently demanding solutions in international medical communities. In the face of the challenge of accelerating global population aging， in-depth exploration of aging mechanisms and the development of effective intervention strategies hold significant scientific and clinical value. This study supported by the national key research and development program of China， employed the essence-Qi-spirit theory of Qiluo doctrine as its guiding framework， focusing on the key scientific issue of the core traditional Chinese pathogenesis of aging， namely "depletion of kidney essence， deficiency of primordial Qi， and impairment of body and spirit". The treatment principle of "tonifying the kidney to replenish essence， harmonizing Yin and Yang， warming and invigorating primordial Qi， and nourishing the body and spirit" was established. Centered on holistic aging， systemic aging， and aging-related diseases， the research integrated multidisciplinary research approaches to construct multi-modal aging models and a multi-dimensional evaluation system， and it utilized multi-omics technologies to deeply analyze aging mechanisms. By systematically reviewing historical kidney-tonifying and anti-aging formulas and combining big data with artificial intelligence technologies， an information database of anti-aging traditional Chinese medicine substance was developed to reveal the differences and synergistic effects of various treatment methods and formulas on anti-aging. Based on this treatment method， the research integrated two millennia of kidney-tonifying medicinal experience to develop the innovative anti-aging traditional Chinese medicine， namely Bazhi Bushen capsules. It was validated that this capsule can delay holistic and systemic aging through multiple targets and mechanisms， thereby elucidating the scientific connotation of the essence-Qi-spirit theory of Qiluo doctrine in guiding anti-aging research from multiple dimensions and providing robust support for leveraging the advantages of traditional Chinese medicine to occupy the commanding heights of international anti-aging research.

ObjectiveThe nucleolar protein PES1 (Pescadillo homolog 1) plays critical roles in ribosome biogenesis and cell cycle regulation, yet its involvement in cellular senescence remains poorly understood. This study aimed to comprehensively investigate the functional consequences of PES1 suppression in cellular senescence and elucidate the molecular mechanisms underlying its regulatory role. MethodsInitially, we assessed PES1 expression patterns in two distinct senescence models: replicative senescent mouse embryonic fibroblasts (MEFs) and doxorubicin-induced senescent human hepatocellular carcinoma HepG2 cells. Subsequently, PES1 expression was specifically downregulated using siRNA-mediated knockdown in these cell lines as well as additional relevant cell types. Cellular proliferation and senescence were assessed by EdU incorporation and SA-β-gal staining assays, respectively. The expression of senescence-associated proteins (p53, p21, and Rb) and SASP factors (IL-6, IL-1β, and IL-8) were analyzed by Western blot or qPCR. Furthermore, Northern blot and immunofluorescence were employed to evaluate pre-rRNA processing and nucleolar morphology. ResultsPES1 expression was significantly downregulated in senescent MEFs and HepG2 cells. PES1 knockdown resulted in decreased EdU-positive cells and increased SA‑β‑gal-positive cells, indicating proliferation inhibition and senescence induction. Mechanistically, PES1 suppression activated the p53-p21 pathway without affecting Rb expression, while upregulating IL-6, IL-1β, and IL-8 production. Notably, PES1 depletion impaired pre-rRNA maturation and induced nucleolar stress, as evidenced by aberrant nucleolar morphology. ConclusionOur findings demonstrate that PES1 deficiency triggers nucleolar stress and promotes p53-dependent (but Rb-independent) cellular senescence, highlighting its crucial role in maintaining nucleolar homeostasis and regulating senescence-associated pathways.

Objective To explore the association of diabetes status with the development of tuberculosis (TB) among the community population in Shanghai, and to provide evidence for the formulation of tuberculosis prevention and control strategies. Methods This population-based cohort study was based on Shanghai Suburban Adult Cohort and Biobank (SSACB) in China. The baseline data were acquired by questionnaires, physical examinations and blood biochemistry tests. TB incidence was obtained by matching with TB management information system data. A Cox proportional risk model was established to assess the risk of tuberculosis. Results A total of 36 014 research subjects were included, with an average age of 56.3±11.3 years, of which 14 587 (40.5%) were male. Over 6 years of follow-up, 47 individuals progressed to tuberculosis (incidence rate: 19.8 per 100 000 person-year, 95% CI: 14.6 -26.4). An increased risk of TB was observed in participants with newly diagnosed diabetes compared with those without diabetes (adjusted hazard ratio [aHR], 2.73; 95% CI, 1.19 - 6.28). Conclusion The risk of tuberculosis in newly diagnosed diabetic patients is significantly increased, and strengthening tuberculosis screening for this population should be considered in practical work.

Quantum dots (QDs), nanoscale semiconductor crystals, have emerged as a revolutionary class of nanomaterials with unique optical and electrochemical properties, making them highly promising for applications in disease diagnosis and treatment. Their tunable emission spectra, long-term photostability, high quantum yield, and excellent charge carrier mobility enable precise control over light emission and efficient charge utilization, which are critical for biomedical applications. This article provides a comprehensive review of recent advancements in the use of quantum dots for disease diagnosis and therapy, highlighting their potential and the challenges involved in clinical translation. Quantum dots can be classified based on their elemental composition and structural configuration. For instance, IB-IIIA-VIA group quantum dots and core-shell structured quantum dots are among the most widely studied types. These classifications are essential for understanding their diverse functionalities and applications. In disease diagnosis, quantum dots have demonstrated remarkable potential due to their high brightness, photostability, and ability to provide precise biomarker detection. They are extensively used in bioimaging technologies, enabling high-resolution imaging of cells, tissues, and even individual biomolecules. As fluorescent markers, quantum dots facilitate cell tracking, biosensing, and the detection of diseases such as cancer, bacterial and viral infections, and immune-related disorders. Their ability to provide real-time, in vivo tracking of cellular processes has opened new avenues for early and accurate disease detection. In the realm of disease treatment, quantum dots serve as versatile nanocarriers for targeted drug delivery. Their nanoscale size and surface modifiability allow them to transport therapeutic agents to specific sites, improving drug bioavailability and reducing off-target effects. Additionally, quantum dots have shown promise as photosensitizers in photodynamic therapy (PDT). When exposed to specific wavelengths of light, quantum dots interact with oxygen molecules to generate reactive oxygen species (ROS), which can selectively destroy malignant cells, vascular lesions, and microbial infections. This targeted approach minimizes damage to healthy tissues, making PDT a promising strategy for treating complex diseases. Despite these advancements, the translation of quantum dots from research to clinical application faces significant challenges. Issues such as toxicity, stability, and scalability in industrial production remain major obstacles. The potential toxicity of quantum dots, particularly to vital organs, has raised concerns about their long-term safety. Researchers are actively exploring strategies to mitigate these risks, including surface modification, coating, and encapsulation techniques, which can enhance biocompatibility and reduce toxicity. Furthermore, improving the stability of quantum dots under physiological conditions is crucial for their effective use in biomedical applications. Advances in surface engineering and the development of novel encapsulation methods have shown promise in addressing these stability concerns. Industrial production of quantum dots also presents challenges, particularly in achieving consistent quality and scalability. Recent innovations in synthesis techniques and manufacturing processes are paving the way for large-scale production, which is essential for their widespread adoption in clinical settings. This article provides an in-depth analysis of the latest research progress in quantum dot applications, including drug delivery, bioimaging, biosensing, photodynamic therapy, and pathogen detection. It also discusses the multiple barriers hindering their clinical use and explores potential solutions to overcome these challenges. The review concludes with a forward-looking perspective on the future directions of quantum dot research, emphasizing the need for further studies on toxicity mitigation, stability enhancement, and scalable production. By addressing these critical issues, quantum dots can realize their full potential as transformative tools in disease diagnosis and treatment, ultimately improving patient outcomes and advancing biomedical science.

Artificial intelligence (AI), particularly deep learning, has demonstrated remarkable performance in medical imaging across a variety of modalities, including X-ray, computed tomography (CT), magnetic resonance imaging (MRI), ultrasound, positron emission tomography (PET), and pathological imaging. However, most existing state-of-the-art AI techniques are task-specific and focus on a limited range of imaging modalities. Compared to these task-specific models, emerging foundation models represent a significant milestone in AI development. These models can learn generalized representations of medical images and apply them to downstream tasks through zero-shot or few-shot fine-tuning. Foundation models have the potential to address the comprehensive and multifactorial challenges encountered in clinical practice. This article reviews the clinical applications of both task-specific and foundation models, highlighting their differences, complementarities, and clinical relevance. We also examine their future research directions and potential challenges. Unlike the replacement relationship seen between deep learning and traditional machine learning, task-specific and foundation models are complementary, despite inherent differences. While foundation models primarily focus on segmentation and classification, task-specific models are integrated into nearly all medical image analyses. However, with further advancements, foundation models could be applied to other clinical scenarios. In conclusion, all indications suggest that task-specific and foundation models, especially the latter, have the potential to drive breakthroughs in medical imaging, from image processing to clinical workflows.
Humans ; Artificial Intelligence ; Deep Learning ; Diagnostic Imaging/methods* ; Magnetic Resonance Imaging ; Tomography, X-Ray Computed ; Positron-Emission Tomography

The development of bone in human body and the maintenance of bone mass in adulthood are regulated by a variety of biological factors. Myocyte enhancer factor 2C (MEF2C), as one of the many factors regulating bone tissue development and balance, has been shown to play a key role in bone development and metabolism. However, there is limited systematic analysis on the effects of MEF2C on bone tissue. This article reviews the role of MEF2C in bone development and metabolism. During bone development, MEF2C promotes the development of neural crest cells (NC) into craniofacial cartilage and directly promotes cartilage hypertrophy. In terms of bone metabolism, MEF2C exhibits a differentiated regulatory model across different types of osteocytes, demonstrating both promoting and other potential regulatory effects on bone formation, with its stimulating effect on osteoclasts being determined. In view of the complex roles of MEF2C in bone tissue, this paper also discusses its effects on some bone diseases, providing valuable insights for the physiological study of bone tissue and strategies for the prevention of bone diseases.
Humans ; MEF2 Transcription Factors/physiology* ; Bone and Bones/metabolism* ; Animals ; Bone Development/physiology* ; Osteogenesis/physiology* ; Myogenic Regulatory Factors/physiology*

This study aims to explore the medication rules and mechanisms of treating chronic renal failure(CRF) by Jinling medical school based on data mining, network pharmacology, and experimental validation systematically and deeply. Firstly, the study selected the papers published by the inherited clinicians in Jinling medical school in Chinese journals using the subject headings named "traditional Chinese medicine(TCM) + chronic renal failure", "TCM + chronic renal inefficiency", or "TCM + consumptive disease" in China National Knowledge Infrastructure, Wanfang, and VIP Chinese Science and Technology Periodical Database and screened TCM formulas for treating CRF according to inclusion and exclusion criteria. The study analyzed the frequency of use of single TCM and the four properties, five tastes, channel tropism, and efficacy of TCM used with high frequency and performed association rule and clustering analysis, respectively. As a result, a total of 215 TCM formulas and 235 different single TCM were screened, respectively. The TCM used with high frequency included Astragali Radix, Rhei Radix et Rhizoma, Salviae Miltiorrhizae Radix et Rhizoma, Poria, and Atractylodis Macrocephalae Rhizoma(top 5). The single TCM characterized by "cold properties, sweet flavor, and restoring spleen channel" and the TCM with the efficacy of tonifying deficiency had the highest frequency of use, respectively. Then, the TCM with the rules of "blood-activating and stasis-removing" and "diuretic and dampness-penetrating" appeared. In addition, the core combination of TCM [(Hexin Formula, HXF)] included "Astragali Radix, Rhei Radix et Rhizoma, Poria, Salviae Miltiorrhizae Radix, and Angelicae Sinensis Radix". The network pharmacology analysis showed that HXF had 91 active compounds and 250 corresponding protein targets including prostaglandin-endoperoxide synthase 2(PTGS2), PTGS1, sodium voltage-gated channel alpha subunit 5(SCN5A), cholinergic receptor muscarinic 1(CHRM1), and heat shock protein 90 alpha family class A member 1(HSP90AA1)(top 5). Gene Ontology(GO) function analysis revealed that the core targets of HXF predominantly affected biological processes, cellular components, and molecular functions such as positive regulation of transcription by ribonucleic acid polymerase Ⅱ and DNA template transcription, formation of cytosol, nucleus, and plasma membrane, and identical protein binding and enzyme binding. Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis revealed that CRF-related genes were involved in a variety of signaling pathways and cellular metabolic pathways, primarily involving "phosphatidylinositol 3-kinase(PI3K)-protein kinase B(Akt) pathway" and "advanced glycation end products-receptor for advanced glycation end products". Molecular docking results showed that the active components in HXF such as isomucronulatol 7-O-glucoside, betulinic acid, sitosterol, and przewaquinone B might be crucial in the treatment of CRF. Finally, a modified rat model with renal failure induced by adenine was used, and the in vivo experimental confirmation was performed based on the above-mentioned predictions. The results verify that HXF can regulate mitochondrial autophagy in the kidneys and the PI3K-Akt-mammalian target of rapamycin(mTOR) signaling pathway activation at upstream, so as to alleviate renal tubulointerstitial fibrosis and then delay the progression of CRF.
Data Mining ; Drugs, Chinese Herbal/chemistry* ; Network Pharmacology ; Humans ; Kidney Failure, Chronic/metabolism* ; Medicine, Chinese Traditional ; China

Medical institutions, with their clinical practice foundation and abundant human use experience data, have become important carriers for the inheritance and innovation of traditional Chinese medicine(TCM) and the "cradles" of the preparation of new TCM. To effectively promote the transformation of new TCM originating from the TCM clinical practice in medical institutions and establish an effective evaluation index system for the transformation of new TCM conforming to the characteristics of TCM, consensus experts adopted the literature research, questionnaire survey, Delphi method, etc. By focusing on the policy and technical evaluation of new TCM originating from the TCM clinical practice in medical institutions, a comprehensive evaluation from the dimensions of drug safety, efficacy, feasibility, and characteristic advantages was conducted, thus forming a comprehensive evaluation system with four primary indicators and 37 secondary indicators. The expert consensus reached aims to encourage medical institutions at all levels to continuously improve the high-quality research and development and transformation of new TCM originating from the TCM clinical practice in medical institutions and targeted at clinical needs, so as to provide a decision-making basis for the preparation, selection, cultivation, and transformation of new TCM for medical institutions, improve the development efficiency of new TCM, and precisely respond to the public medication needs.
Medicine, Chinese Traditional/standards* ; Humans ; Consensus ; Drugs, Chinese Herbal/therapeutic use* ; Surveys and Questionnaires