[摘 要] 目的：探讨lncRNA DLEU2通过EZH2/H3K27me3途径调控IKKα介导甲状腺癌（TC）放射性碘抵抗的作用机制。方法：利用TCGA数据库分析TC中DLEU2的表达及其与EZH2的相关性。构建放射性碘抵抗的TPC-1细胞（RR-TPC-1细胞）模型及裸鼠移植瘤模型，通过敲低或过表达DLEU2（si-DLEU2/OE-DLEU2）、抑制EZH2（UNC1999）、过表达IKKα（OE-IKKα）进行干预，采用qPCR、WB、RIP、ChIP、CCK-8、流式细胞术、TUNEL染色及体内成瘤实验检测基因与蛋白表达、表观修饰、细胞增殖、凋亡及肿瘤生长。结果：TCGA分析显示，DLEU2在TC组织中显著上调（P < 0.001），与患者不良预后相关（P = 0.008 4），且与EZH2表达呈正相关（r = 0.390, P < 0.001）；RIP证实EZH2与DLEU2存在相互作用/结合（P < 0.05）。体外实验表明，敲低DLEU2可显著下调RR-TPC-1细胞中EZH2、IKKα表达及H3K27me3修饰水平，抑制NF-κB通路活化（P < 0.05或P < 0.01），抑制细胞增殖、促进凋亡（均P < 0.05）。联合敲低DLEU2与抑制EZH2进一步增强上述效应，而过表达IKKα则可部分逆转上述效应（P < 0.05或P < 0.01）。体内实验进一步证实，敲低DLEU2联合抑制EZH2可显著抑制移植瘤生长，增加肿瘤细胞凋亡（均P < 0.01）；IKKα过表达则部分逆转上述抗肿瘤效应（P < 0.05或P < 0.01）。结论：lncRNA DLEU2通过招募EZH2催化H3K27me3修饰，间接激活IKKα/NF-κB信号并形成正反馈环路，介导TPC-1细胞131I抵抗。

ObjectiveTo systematically compare the effects of diverse electromagnetic stimulation protocols on hand function and activities of daily living (ADL) in stroke patients using network meta-analysis (NMA), and screen the optimal stimulation strategy for post-stroke hand dysfunction rehabilitation. MethodsNMA was performed in accordance with the PRISMA-NMA statement. Databases of CNKI, Wanfang data, VIP, CBM, PubMed, Web of Science and Embase were searched from database inception to April, 2026 for eligible randomized controlled trials (RCTs) comparing different electromagnetic stimulation protocols for post-stroke hand impairment. The Cochrane Risk of Bias tool and PEDro scale were used to assess methodological quality of included studies, while the GRADE system was adopted to grade evidence quality of primary outcomes of Fugl-Meyer Assessment-Upper Extremities (FMA-UE) and modified Barthel Index (MBI). After literature screening, data extraction and bias evaluation, RevMan 5.4 and Stata 17.0 were used for meta-analysis and NMA. ResultsA total of 22 RCT involving 17 electromagnetic stimulation protocols were finally included. The PEDro scores ranged from six to ten. The top five protocols for improving FMA-UE score were repetitive peripheral magnetic stimulation (rPMS) + repetitive transcranial magnetic stimulation (rTMS), intermittent theta-burst stimulation (iTBS) + rPMS, iTBS + transcranial direct current stimulation (tDCS), transcutaneous electrical acupoint stimulation (TEAS) and contralaterally controlled functional electrical stimulation (CCFES). tDCS was the most effective on MBI, followed by TEAS and iTBS+rPMS. Evidence quality for FMA-UE and MBI was moderate. Funnel plots suggested low risk of publication bias, and consistency tests verified good coherence between direct and indirect comparisons in network models. ConclusionElectromagnetic stimulation significantly facilitates upper limb and hand functional recovery, and improves ADL in stroke patients. The combined central-peripheral magnetic stimulation protocol may be the most effective on motor rehabilitation, whereas tDCS on ADL.

Metabolic diseases characterized by an imbalance in energy homeostasis represent a significant global health challenge. Individuals with metabolic diseases often suffer from complications related to disorders in lipid metabolism, such as obesity and non-alcoholic fatty liver disease (NAFLD). Understanding core genes involved in lipid metabolism can advance strategies for the prevention and treatment of these conditions. Stearoyl-CoA desaturase 1 (SCD1) is a key enzyme in lipid metabolism that converts saturated fatty acids into monounsaturated fatty acids. SCD1 plays a crucial regulatory role in numerous physiological and pathological processes, including energy homeostasis, glycolipid metabolism, autophagy, and inflammation. Abnormal transcription and epigenetic activation of Scd1 contribute to abnormal lipid accumulation by regulating multiple signaling axes, thereby promoting the development of obesity, NAFLD, diabetes, and cancer. This review comprehensively summarizes the key role of SCD1 as a metabolic hub gene in various (patho)physiological contexts. Further it explores potential translational avenues, focusing on the development of novel SCD1 inhibitors across interdisciplinary fields, aiming to provide new insights and approaches for targeting SCD1 in the prevention and treatment of metabolic diseases.
Stearoyl-CoA Desaturase/metabolism* ; Humans ; Metabolic Diseases/physiopathology* ; Lipid Metabolism/physiology* ; Animals ; Obesity/enzymology* ; Non-alcoholic Fatty Liver Disease

Aromatic immunity in traditional Chinese medicine(TCM) is the medical knowledge accumulated in the process of people's struggling with diseases. It plays an important role in plague prevention, disease treatment, health preservation, and rehabilitation, and has profound TCM basic theoretical support and abundant modern scientific evidence. With the in-depth promotion of the Healthy China initiative and the succession of health needs in the post-COVID-19 era, how to practice the health concept of aromatic immunity in TCM and develop its health service resources with high quality has become an important proposition to be discussed urgently. This paper summarizes the cognitive process, puts forward the basic concept, discusses the scientific connotation and clinical application value, and looks forward to the future development trend of aromatic immunity in TCM, aiming to provide guidance for the development of great health products and promote the application of aromatic immunity in TCM in serving people's health.
Medicine, Chinese Traditional/methods* ; Humans ; COVID-19/immunology* ; China ; Drugs, Chinese Herbal/therapeutic use* ; SARS-CoV-2

This research investigated the impact of Ganoderma lucidum polysaccharides(GLP) on hepatoblastoma HepG2 and Huh6 cell models, as well as KM mouse model with in situ transplanted tumors, so as to provide a theoretical basis for the clinical application of GLP. Cell viability was assessed through the CCK-8 assay, whereas cell proliferation was evaluated by using the BeyoClick~(TM)EdU-488 test. Cell apoptosis was visualized via Hochest 33258 staining, and autophagy was detected through Mrfp-GFP-LC3 dual fluorescence staining. An in situ tumor transplantation model was created by using HepG2 cells in mice, and mice were treated with normal saline and GLP of 100, 200, and 300 mg·kg~(-1) for tumor count calculation and size assessment. Hematoxylin-eosin(HE) staining was used to observe pathological changes in tumor tissue and vital organs(liver, kidney, lung, spleen, and heart). Western blot analysis was conducted to measure the protein expressions of tumor protein P53(P53), B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), cleaved-caspase-3, Beclin-1, autophagy related protein-5(Atg-5), microtubule-associated protein-light chain-3Ⅰ(LC3Ⅰ)/LC3Ⅱ, autophagy adapter protein 62(P62), protein kinase B(Akt), p-Akt, mammalian target of rapamycin(mTOR), and p-mTOR. The in vitro experiment revealed that compared with the control group, after GLP treatment, tumor cell viability decreased significantly; apoptosis rate increased in a dose-dependent manner, and autophagic flux was inhibited. The in vivo experiments showed that compared with the model group, mice treated with GLP exhibited significantly fewer and smaller tumors. Western blot results showed that compared with the control group or model group, levels of P53, Bax, cleaved-caspase-3, Beclin-1, Atg-5, and LC3-Ⅱ/LC3-Ⅰ were significantly increased after GLP treatment, and the levels of Bcl-2, P62, p-Akt/Akt, and p-mTOR/mTOR were significantly decreased. These outcomes suggest that GLP promotes apoptosis and autophagy in hepatoblastoma cells by regulating the Akt/mTOR pathway.
Animals ; Humans ; Autophagy/drug effects* ; Reishi/chemistry* ; Mice ; Apoptosis/drug effects* ; TOR Serine-Threonine Kinases/genetics* ; Proto-Oncogene Proteins c-akt/genetics* ; Liver Neoplasms/genetics* ; Hepatoblastoma/genetics* ; Polysaccharides/pharmacology* ; Cell Line, Tumor ; Signal Transduction/drug effects* ; Male ; Cell Proliferation/drug effects* ; Hep G2 Cells

This study investigates the mechanism by which Xintong Granules improve myocardial ischemia-reperfusion injury(MIRI) through the regulation of gut microbiota and their metabolites, specifically short-chain fatty acids(SCFAs). Rats were randomly divided based on body weight into the sham operation group, model group, low-dose Xintong Granules group(1.43 g·kg~(-1)·d~(-1)), medium-dose Xintong Granules group(2.86 g·kg~(-1)·d~(-1)), high-dose Xintong Granules group(5.72 g·kg~(-1)·d~(-1)), and metoprolol group(10 mg·kg~(-1)·d~(-1)). After 14 days of pre-administration, the MIRI rat model was established by ligating the left anterior descending coronary artery. The myocardial infarction area was assessed using the 2,3,5-triphenyltetrazolium chloride(TTC) staining method. Apoptosis in tissue cells was detected by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL) assay. Pathological changes in myocardial cells and colonic tissue were observed using hematoxylin-eosin(HE) staining. The levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), interleukin-6(IL-6), creatine kinase MB isoenzyme(CK-MB), and cardiac troponin T(cTnT) in rat serum were quantitatively measured using enzyme-linked immunosorbent assay(ELISA) kits. The activities of lactate dehydrogenase(LDH), creatine kinase(CK), and superoxide dismutase(SOD) in myocardial tissue, as well as the level of malondialdehyde(MDA), were determined using colorimetric assays. Gut microbiota composition was analyzed by 16S rDNA sequencing, and fecal SCFAs were quantified using gas chromatography-mass spectrometry(GC-MS). The results show that Xintong Granules significantly reduced the myocardial infarction area, suppressed cardiomyocyte apoptosis, and decreased serum levels of pro-inflammatory cytokines(TNF-α, IL-1β, and IL-6), myocardial injury markers(CK-MB, cTnT, LDH, and CK), and oxidative stress marker MDA. Additionally, Xintong Granules significantly improved intestinal inflammation in MIRI rats, regulated gut microbiota composition and diversity, and increased the levels of SCFAs(acetate, propionate, isobutyrate, etc.). In summary, Xintong Granules effectively alleviate MIRI symptoms. This study preliminarily confirms that Xintong Granules exert their inhibitory effects on MIRI by regulating gut microbiota imbalance and increasing SCFA levels.
Animals ; Gastrointestinal Microbiome/drug effects* ; Rats ; Male ; Myocardial Reperfusion Injury/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Apoptosis/drug effects* ; Humans ; Tumor Necrosis Factor-alpha/metabolism* ; Interleukin-6/genetics* ; Malondialdehyde/metabolism*

Osteoporotic fractures(OPF) refer to the fractures caused by minor violence in the state of osteoporosis, seriously threatening the life and health of elderly patients. Drug and surgical therapies have limitations such as single targets, diverse adverse reactions, and poor prognosis. Kidney-tonifying traditional Chinese medicine(TCM) has good potential in the treatment of OPF. TCM can promote the healing of OPF by promoting angiogenesis in the early stage of bone healing, promoting osteogenic differentiation of bone marrow mesenchymal stem cells in the stage of bone repair, maintaining the balance of osteogenic and osteoclastic system in the stage of bone remodeling, and regulating the oxidative stress responses throughout the process of OPF healing. TCM can alleviate the pathological state of osteoporosis and promote fracture healing in OPF patients via multiple pathways and targets, demonstrating the advantages and potential of biphasic regulation.
Humans ; Drugs, Chinese Herbal/therapeutic use* ; Osteoporotic Fractures/metabolism* ; Animals ; Fracture Healing/drug effects* ; Medicine, Chinese Traditional ; Kidney/metabolism* ; Osteogenesis/drug effects*

Cytotoxic CD4⁺ T cells (CD4⁺ CTLs) represent a novel subset of T cells with cytotoxic effects. They recognize target cells in an antigen-specific manner, relying on class II major histocompatibility complex (MHC-II) interactions. CD4⁺ CTLs exert cytotoxic effects on target cells by secreting cytotoxic molecules such as granzymes, perforin, and granulysin. Recent studies have revealed their significant roles in various autoimmune diseases. This review focuses on the differentiation, phenotypic characteristics, and roles of CD4⁺ CTLs in different types of autoimmune disorders, aiming to provide new insights for the prevention and treatment of these diseases.
Humans ; Autoimmune Diseases/immunology* ; CD4-Positive T-Lymphocytes/immunology* ; Animals ; T-Lymphocytes, Cytotoxic/immunology* ; Perforin/immunology* ; Granzymes/immunology*

Objective Based on 25 indicators including immune factors, cell count classification, and smear results of the knee joint fluid, machine learning models were established to distinguish between osteoarthritis (OA) and rheumatoid arthritis (RA). Methods 100 OA and 40 RA patients scheduled for total knee arthroplasty were enrolled respectively. Each patient's knee joint fluid was collected preoperatively. Nucleated cells were counted and classified. The expression levels of immune factors, including tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), IL-6, IL-8, IL-15, matrix metalloproteinase 3 (MMP3), MMP9, MMP13, rheumatoid factor (RF), serum amyloid A (SAA), C-reactive protein (CRP), and others were measured. Smears and microscopic classification of all the immune factors were performed. Independent influencing factors for OA or RA were identified using univariate binary logistic regression, Lasso regression, and multivariate binary logistic regression. Based on the independent influencing factors, three machine learning models were constructed which are logistic regression, random forest, and support vector machine. Receiver operating characteristic curve (ROC), calibration curve and decision curve analysis (DCA) were used to evaluate and compare the models. Results A total of 5 indicators in the knee joint fluid were screened out to distinguish OA and RA, which were IL-1β(odds ratio(OR)=10.512, 95× confidence interval (95×CI) was 1.048-105.42, P=0.045), IL-6 (OR=1.007, 95×CI was 1.001-1.014, P=0.022), MMP9 (OR=3.202, 95×CI was 1.235-8.305, P=0.017), MMP13 (OR=1.002, 95× CI was 1-1.004, P=0.049), and RF (OR=1.091, 95×CI was 1.01-1.179, P=0.026). According to the results of ROC, calibration curve and DCA, the accuracy (0.979), sensitivity (0.98) and area under the curve (AUC, 0.996, 95×CI was 0.991-1) of the random forest model were the highest. It has good validity and feasibility, and its distinguishing ability is better than the other two models. Conclusion The machine learning model based on immune factors in the knee joint fluid holds significant value in distinguishing OA and RA. It provides an important reference for the clinical early differential diagnosis, prevention and treatment of OA and RA.
Humans ; Arthritis, Rheumatoid/metabolism* ; Machine Learning ; Male ; Female ; Middle Aged ; Aged ; Synovial Fluid/immunology* ; Osteoarthritis, Knee/metabolism* ; Knee Joint/metabolism* ; ROC Curve ; Diagnosis, Differential

OBJECTIVES: To investigate the chain mediating role of family care and emotional management in the relationship between social support and anxiety among rural primary school students. METHODS: A questionnaire survey was conducted among students in grades 4 to 6 from four counties in Hunan Province. Data were collected using the Social Support Rating Scale, Family Care Index Scale, Emotional Intelligence Scale, and Generalized Anxiety Disorder -7. Logistic regression analysis was used to explore the influencing factors of anxiety symptoms. Mediation analysis was conducted to assess the chain mediating effects of family care and emotional management between social support and anxiety. RESULTS: A total of 4 141 questionnaires were distributed, with 3 874 valid responses (effective response rate: 93.55%). The prevalence rate of anxiety symptoms among these students was 9.32% (95%CI: 8.40%-10.23%). Significant differences were observed in the prevalence rates of anxiety symptoms among groups with different levels of social support, family functioning, and emotional management ability (P<0.05). The total indirect effect of social support on anxiety symptoms via family care and emotional management was significant (β=-0.137, 95%CI: -0.167 to -0.109), and the direct effect of social support on anxiety symptoms remained significant (P<0.05). Family care and emotional management served as significant chain mediators in the relationship between social support and anxiety symptoms (β=-0.025,95%CI:-0.032 to -0.018), accounting for 14.5% of the total effect. CONCLUSIONS Social support can directly affect anxiety symptoms among rural primary school students and can also indirectly influence anxiety symptoms through the chain mediating effects of family care and emotional management. These findings provide scientific evidence for the prevention of anxiety in primary school students from multiple perspectives.
Humans ; Female ; Male ; Social Support ; Anxiety/etiology* ; Child ; Students/psychology* ; Emotions ; Logistic Models