ObjectiveTo systematically compare the differential regulation of the maternal-fetal interface cell lineages and communication networks in the CBA/J×DBA/2 mouse model of recurrent pregnancy loss （RPL） by the two classic therapeutic methods-tonifying the kidney to stabilize the fetus and invigorating the spleen to stabilize the fetus （Shoutai Wan， Juyuan Jian）-of traditional Chinese medicine （TCM） at the single-cell resolution and clarify their modern scientific connotations. MethodsFemale non-pregnant CBA/J mice were caged with male BALB/c （blank group） and DBA/2 （modeling group） mice separately. Pregnant mice in the modeling group were randomly grouped as follows： high/low-dose Shoutai Wan， high/low-dose Juyuan Jian， model （RPL）， and positive control （dydrogesterone）， with 10 mice in each group. Starting from the day after the detection of the vaginal plug， mice were administrated with drugs or an equal volume of normal saline by gavage for 10 consecutive days. After the intervention， the following indicators were measured. ① Macroscopic evaluation： general conditions， uterine wet weight， embryo loss rate， four coagulation parameters ［prothrombin time （PT）， activated partial thromboplastin time （APTT）， fibrinogen （FIB）， and thrombin time （TT）］， and peripheral blood estradiol （E₂） and progesterone （Pg） levels. The decidua with embryos was stained with hematoxylin-eosin （HE） and evaluated by transmission electron microscopy （TEM）. The expression of B-cell lymphoma-2 （Bcl-2）， vascular endothelial growth factor （VEGF）， angiotensin Ⅱ （AngⅡ）， matrix metalloproteinase-2 （MMP-2）， interleukin-6 （IL-6）， leukemia inhibitory factor （LIF）， CXC chemokine ligand 12 （CXCL12）， and microtubule-associated protein 1 light chain 3 homolog （LC3）Ⅰ/Ⅱ was quantified by Western blot. ② Mechanism analysis at the single-cell level： The decidua with embryos from the blank， model， high-dose Shoutai Wan， and high-dose Juyuan Jian groups （6 mice per group， with 3 single-cell samples per group， totaling 24 mice） were analyzed by the BD Rhapsody™ platform， and the whole-cell atlas was drawn by uniform manifold approximation and projection （UMAP） dimensionality reduction clustering combined with the single-cell mouse cell atlas （scMCA）. The differentially expressed genes （DEGs） and cell interaction networks were analyzed via Gene Ontology （GO）， Kyoto Encyclopedia of Genes and Genomes （KEGG）， and CellChat， and the protein-protein interaction （PPI） map of subtype cells was constructed. The CytoTRACE pseudo-temporal analysis was performed to explore the developmental trajectories of core immune cells （natural killer cells， NK cells） from maternal and fetal sources. Results① Pathological and Western blot results indicated that compared with the blank group， the RPL group showed an increase in the embryo loss rate （P<0.01）， down-regulated expression of Bcl-2， LIF， MMP-2， and Vegf in the decidua with embryos （P<0.05）， up-regulated protein levels of CXCL-12， AngⅡ， and IL-6 （P<0.05）， blocked angiogenesis， apoptosis-inflammation imbalance， and coagulation dysfunction. Both prescriptions dose-dependently reduced the abortion rate and restored the angiogenesis-inflammation balance， and Shoutai pill showed superior performance in restoring the E₂ level to the Pg level （P<0.05）. ② Single-cell transcriptome analysis indicated that compared with the blank group， the RPL group showed differences in multiple key cell populations such as decidual cells， trophoblast cells， endothelial cells， erythroblasts， NK cells， and macrophages at the maternal-fetal interface. Immunity and angiogenesis were the key links in RPL. Compared with the RPL group， high-dose Shoutai Wan reversed the changes of NK cells in the embryonic layer （upregulating the mRNA levels of 17 genes and downregulating the mRNA levels of 29 genes） and macrophages （upregulating the mRNA levels of 117 genes and downregulating the mRNA levels of 53 genes） through the regulation of gene expression. High-dose Shoutai pill regulated the immune cells to affect unfolded proteins， cell adhesion， and programmed cell death， thereby promoting decidualization and angiogenesis and modulating embryo-membrane development. High-dose Juyuan Jian regulated the key subgroups of NK cells （up-regulating the mRNA levels of 9 genes and down-regulating the mRNA levels of 17 genes） and macrophages （up-regulating the mRNA levels of 110 genes and down-regulating the mRNA levels of 81 genes）， which affected decidual inflammation and apoptosis and intervened in glycolysis. ③ The pseudo-temporal analysis and communication network indicated that the communication frequency of the RPL group decreased. High-dose Shoutai Wan restored maternal-fetal tolerance through pathways such as NKG2D， CDH5， GDF， and FASLG. High-dose Juyuan Jian enhanced the IL-6/LIFR/JAK/signal transducer and activator of transcription 3 （STAT3） and desmosome/SEMA6/tumor necrosis factor-like weak inducer of apoptosis （TWEAK） signaling to improve endometrial receptivity. The RPL group showed an increased proportion of toxic dNK7， a decreased proportion of reparative dNK4， and blocked embryo fNK1. High-dose Shoutai Wan down-regulated dNK7 and up-regulated dNK4. High-dose Juyuan Jian inhibited the terminal differentiation of dNK7 and up-regulated LILRB1， thus restoring the balance of cytotoxicity and repair. ConclusionBoth the kidney-tonifying and spleen-invigorating methods are effective in treating RPL. NK and macrophages are the key immune cells in the interaction between the embryo and the membrane. The kidney-tonifying method （Shoutai Wan） has an advantage in regulating the phenotypes of unfolded protein， cell adhesion， and programmed cell death， and shows expression characteristics closer to the physiological state in the regulation of NKG2D and CDH5 signals. The spleen-invigorating method （Juyuan Jian） has an advantage in regulating epithelial-mesenchymal transition （EMT）， angiogenesis， and glycolysis and shows higher communication intensity in the IL-6 and LIFR pathways.

[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 analyze the current research status, hotspots and future trends of the application of digital health technology (DHT) in the rehabilitation of upper limb motor function after stroke. MethodsRelevant literature on the application of DHT in upper limb motor rehabilitation for stroke patients published between January, 2015 and December, 2025 was retrieved from Web of Science Core Collection, CNKI and Wanfang database. CiteSpace 6.4.R1 was used for visualized bibliometric analysis. ResultsA total of 1 295 publications were included, comprising 454 in Chinese and 841 in English. The annual number of publications generally showed an upward trend. China ranked first in publication output in English literature. The institutions with the highest numbers of publications were Huashan Hospital Affiliated to Fudan University and Swiss Federal Institute of Technology in Zurich. Both Chinese and English keywords formed ten clustering groups. Chinese clusters mainly involved occupational therapy, neural mechanisms and home-based rehabilitation, whereas English clusters focused on virtual reality, brain-computer interfaces and machine learning. High-frequency keywords included virtual reality, brain-computer interface, machine learning and deep learning. Chinese keywords with a strong burst included rehabilitation training, while deep learning showed a strong burst in English keywords. Stroke was the most frequently cited journal. Highly cited journals covered multiple disciplines, including rehabilitation medicine, neuroscience and computer science, reflecting the interdisciplinary characteristics of this field. ConclusionResearches on DHT for upper limb motor function rehabilitation in stroke are increasing annually, focusing on core interaction technologies, neural mechanism and artificial intelligence. Future research trends may include inter-disciplinary integration of artificial intelligence with core rehabilitation technologies, neuroimaging-guided targeted interventions, optimisation of home-based rehabilitation systems, and development of multidimensional quantitative assessment models.

AIM:To analyze the efficacy of modified Zhujing formula combined with intravitreal ranibizumab(IVR)injection in the treatment of wet age-related macular degeneration(wARMD).METHODS: A prospective study was conducted on wARMD patients at the Ophthalmology Department of Yulin Hospital of Traditional Chinese Medicine from September 2022 to October 2024. The study subjects were divided into the experimental group and the control group according to the random number table method. The control group received IVR treatment, while the experimental group was treated with modified Zhujing formula in addition to IVR injection. The clinical efficacy, TCM symptom scores, central retinal thickness(CRT), best corrected visual acuity(BCVA), macular hemorrhage area, choroidal neovascularization area(CNV), ocular hemodynamic parameters [resistance index(RI), maximum diastolic blood flow(EDV), maximum systolic blood flow(PSV)], and 1-year recurrence rate were compared between the two groups.RESULTS: This study included 60 eyes from 60 wARMD patients. Among them, the control group consisted of 30 patients and 30 eyes, while the experimental group consisted of 30 patients and 30 eyes. The age of the control group was 67.52±3.12 y, with 17 males and 13 females. The age of the experimental group was 67.62±3.04 y, with 18 males and 12 females.The clinical efficacy of the experimental group(97%)was higher than that of the control group(73%)(P<0.05). After treatment, the scores of blurred vision, soreness and weakness of the waist and knees, restlessness and insomnia, dizziness and tinnitus in the experimental group were all lower than those in the control group(all P<0.05); the EDV and PSV in the experimental group were both higher than those in the control group(both P<0.05); the BCVA, CRT, macular hemorrhage area, CNV and RI of the experimental group were all lower than those of the control group(all P<0.05), and the 1-year recurrence rate in the experimental group(3%)was lower than that in the control group(27%)(P<0.05). CONCLUSION:The combined use of modified Zhujing formula and IVR can effectively alleviate symptoms such as blurred vision and retinal hemorrhage in wARMD patients, improve vision and ocular hemodynamic conditions, and reduce the recurrence rate. This suggests that there may be a synergistic enhancing effect.

Background Prenatal chronic psychological stress may increase the risk of allergic diseases in children, and eczema is the most common allergic disease in children, the pathogenesis of which is not yet fully understood. Objective To preliminarily clarify the changes in offspring intestinal flora after chronic stress exposure during pregnancy in rats that increases offspring immune imbalance and eczema susceptibility. Methods Thirty SPF-grade adult female SD rats were selected and randomly divided into a model group and a control group (n=15). Sixteen male rats were randomly divided into a model mating group and a control mating group (n=8). A 28-day chronic unpredictable mild stress (CUMS) model during pregnancy was established. On the 7th day of stress, male and female rats were caged in a ratio of 3:1. Blood samples were collected from female rats in each group via angular vein on the 1st day before stress, and on the 7th, 14th, 21st, and 28th days after stress. The content of plasma corticosterone during pregnancy was determined by enzyme-linked immunosorbent assay (ELISA). For the offspring rats, an eczema model was constructed using 2,4-dinitrochlorobenzene (DNCB). The number of scratching times of the offspring rats within 5 min was recorded. The offspring rats were divided into 4 groups: DNCB-CUMS group (MM), DNCB-control group (MC), solvent control-CUMS group (CM), and blank control group (CC), with 8 rats in each group. The eczema was induced once every 3 days, and the induction period was 12 d. The expression level of immunoglobulin E (IgE) in the serum of offspring rats after the eczema induction experiment were determined by ELISA. The concentrations of tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-2 (IL-2), interleukin-4 (IL-4), and interleukin-13 (IL-13) in the serum were quantified by multi-parameter flow cytometry. The composition and abundance of intestinal microbiota in the feces of offspring rats were detected by 16S rRNA high-throughput sequencing technology. Results The plasma corticosterone concentrations in the model group were higher than those in the control group on the 7th and 21st days of stress (P<0.05). On the 14th and 21st days of stress, the 1% sucrose preference percentages of female rats in the model group were lower than that in the control group. On the 7th, 14th, and 21st days of stress, the horizontal movement scores of female rats in the model group and the vertical movement scores on the 7th and 14th days were lower than those in the control group (P<0.05). After 6, 9, and 12 d of model building, the scratching frequencies in the MC group and MM group were significantly higher than those in the CC group and CM group (P<0.05). Moreover, there were differences in the contents of cytokines including IFN-γ, IL-2, TNF-α, IL-4, IL-13, and IgE among the offspring rat groups (P<0.05). The CM group and MM group led to an increase in the contents of TNF-α, IL-4, IL-13, and IgE cytokines (P<0.05), while the MM group caused a decrease in the contents of IFN-γ and IL-2 (P<0.05). After the eczema induction experiment, the α-diversity analysis showed that the Simpson index and Shannon index in the CM were higher than those in the CC (P<0.05), indicating that CUMS during the pregnancy of female rats could increase the species abundance of their offspring. The abundances of Prevotella and Lactobacillus in the CM group decreased (P<0.05). Conclusion Intestinal dysbiosis in offspring due to chronic prenatal psychological stress, which may be one of the mechanisms linking maternal stress to immune imbalance and increased susceptibility to eczema in offspring.

Glucagon-like peptide-1 （GLP-1） receptor agonists are a novel class of antidiabetic drugs that also possess lipid- lowering and cardiovascular protective effects， with liraglutide and semaglutide being their representative medications. Based on a systematic literature search， this review summarizes the lipid-lowering mechanisms by which liraglutide and semaglutide exert direct effects on the liver and kidney （regulating autophagy， key lipid metabolism pathways， reverse cholesterol transport， etc.）， direct actions on adipose tissue （affecting adipocyte proliferation and differentiation， expression of lipid metabolism proteins， and gene transcription）， activation of sympathetic pathways through the central nervous system， and modulation of the gut microbiota. Additionally， it summarizes the clinical evidence of their lipid-lowering effects in populations with type 2 diabetes mellitus， overweight individuals， and others. These findings indicate that GLP-1 receptor agonists exert lipid-lowering effects by acting on multiple tissues or systems， providing crucial evidence for further elucidating the molecular mechanisms of these drugs in lipid regulation and exploring potential new ideas for their clinical applications.

ObjectiveTo evaluate the pharmacological effects of verbenalin on both in vitro and in vivo infection models of human coronavirus 229E （HCoV-229E） and to preliminarily explore the antiviral mechanism of verbenalin through proteomic analysis. MethodsIn vitro， the cell counting kit-8 （CCK-8） for cell proliferation and viability assessment was used to establish a model of HCoV-229E-induced injury in human lung adenocarcinoma cells（A549）. A549 cells were divided into five groups： normal group， model group， and three verbenalin treatment groups （125， 62.5， and 31.25 μmol·L^-1）. The cell protective activity of verbenalin was evaluated through cell viability assay and immunofluorescence staining. In vivo， 30 BALB/c mice were randomly divided into normal group， model group， chloroquine group， and high-dose， low-dose verbenalin groups （40 and 20 mg·kg^-1）， with six mice per group. An HCoV-229E-induced mouse lung injury model was established to evaluate the therapeutic effects of verbenalin. Lung injury was assessed by detecting the lung index and lung inhibition rate. The severity of pulmonary inflammation cytokines was measured by enzyme-linked immunosorbent assay （ELISA）， while the lung morphology and structure were analyzed by micro-computed tomography （Micro-CT）. Hematoxylin and eosin （HE） staining was used to assess histopathological changes in lung tissue. Additionally， four-dimensional data-independent acquisition （4D-DIA） proteomics was employed to preliminarily explore the potential mechanisms of verbenalin in treating HCoV-229E-induced lung injury in mice， through differential protein expression screening， functional annotation， enrichment analysis， and protein-protein interaction network analysis. ResultsThe A549 cells were infected with HCoV-229E at the original viral titer for 36 hours to establish an in vitro infection model. The maximum non-toxic concentration of verbenalin was 125 μmol·L^-1， and the half-maximal cytotoxic concentration （CC₅₀） was 288.8 μmol·L^-1. Compared with the normal group， the model group showed a significant decrease in cell viability （P<0.01）， a significant increase in the proportion of dead cells （P<0.01）， mitochondrial damage， and a significant reduction in mitochondrial membrane potential （P<0.01）. After treatment with different concentrations of verbenalin （125， 62.5， and 31.25 μmol·L^-1）， cell viability was significantly increased （P<0.01）， and the proportion of dead cells was reduced （P<0.01）， with mitochondrial membrane potential restored （P<0.01）. In vivo experiments further confirmed the therapeutic effect of verbenalin on HCoV-229E-infected mice. Compared to the normal group， the model group showed a significant increase in the lung index （P<0.01）， severe lung tissue injury， lung volume enlargement， and a significant increase in the expression of inflammatory cytokines， including interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） （P<0.01）. In contrast， in the verbenalin treatment groups， these pathological changes were significantly improved， with a reduction in the lung index （P<0.01）， alleviation of lung tissue injury， reduced lung volume enlargement， and a significant decrease in inflammatory cytokine expression （P<0.01）. Proteomics analysis revealed that， compared to the normal group， the model group showed enrichment in several antiviral immune-related signaling pathways， including the nuclear factor-κB （NF-κB） signaling pathway （P<0.05）. Compared to the model group， the verbenalin treatment group showed enrichment in several signaling pathways related to inflammatory response and autophagy （P<0.05）， suggesting that verbenalin may exert its antiviral and anti-inflammatory effects by regulating these pathways. ConclusionVerbenalin demonstrates significant therapeutic effects in both in vitro and in vivo HCoV-229E infection models， with its mechanism likely related to the NOD-like receptor protein 3 （NLRP3） inflammasome pathway and mitochondrial autophagy.

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*

In recent years, China's manned space program has advanced rapidly, with deep space exploration missions such as manned lunar landing steadily progressing, leading to a significant extension of astronauts' duration in outer space. In this context, the impact of the space magnetic field environment on astronaut health has become increasingly conspicuous. Characterized by its complexity, the spatial magnetic field indirectly regulates the circadian rhythm system by interfering with mitochondrial functions, such as electron transport chain activity, ATP synthesis efficiency, and reactive oxygen species (ROS) balance. This disruption can lead to circadian misalignment, sleep disorders, metabolic dysregulation, and other issues, severely compromising astronauts' physical and mental well-being, as well as mission performance. Currently, researchers have carried out extensive investigations into the influence of the space magnetic environment on circadian rhythms. Nevertheless, due to disparities in magnetic field parameters, exposure durations, and the model organisms employed in experiments, the results have been inconsistent. This review systematically elaborates on ground-based simulation technologies for spatial magnetic field environments and their applications, summarizes the effects of magnetic fields with varying intensities and types on core circadian rhythm biomarkers in model organisms and humans, and explores the underlying molecular and physiological mechanisms of magnetic field-induced circadian rhythm perturbation. This work aims to deepen the understanding of the mechanisms of the space magnetic environment on biological rhythms, and establish a scientific basis for formulating adaptive protective strategies centered on circadian regulation for astronauts, thereby ensuring the successful implementation of long-term deep-space missions.
Circadian Rhythm/physiology* ; Humans ; Magnetic Fields/adverse effects* ; Space Flight ; Animals ; Extraterrestrial Environment