Vascular dementia （VaD） is a cognitive dysfunction syndrome caused by cerebrovascular disease and is the second most common type of dementia worldwide， following Alzheimer's disease. The pathological mechanisms of VaD are complex， involving multiple biological processes， including angiogenesis， neuroinflammation， apoptosis， and oxidative stress. Among these， angiogenesis is a key process in VaD pathology and is primarily regulated through the vascular endothelial growth factor （VEGF） signaling pathway. In recent years， traditional Chinese medicine （TCM） has gradually gained attention in the treatment of VaD， particularly the therapeutic approach of benefiting Qi， activating blood circulation， and resolving blood stasis， which has demonstrated unique advantages in clinical practice. This method， based on the TCM theory of Qi and blood， emphasizes improving the pathological state of ''blood stasis'' by harmonizing the circulation of Qi and blood， and its scientific basis has been increasingly elucidated by modern pharmacological studies. This article systematically integrates the TCM concept of ''removing stasis to promote regeneration'' with the modern medical mechanism of neoangiogenesis and reviews the current research on promoting neoangiogenesis through the benefiting Qi， activating blood circulation， and resolving blood stasis in VaD treatment. It covers research progress on single Chinese medicine and compound formulas that promote neoangiogenesis， reduce apoptosis， and improve cerebral hemodynamics through multi-target and multi-pathway synergistic effects. Furthermore， this article explores the therapeutic approach of combining acupuncture and moxibustion with Chinese medicine formulas， breaking through the traditional single-treatment model. The synergistic treatment of acupuncture and herbal medicine not only enhances neoangiogenesis but also improves cognitive function and quality of life in VaD patients via multiple pathways. By comparing the advantages and limitations of modern medicine and TCM in VaD treatment， this article notes that while modern medicine excels in elucidating pathological mechanisms and targeted therapies， it is limited in overall regulation and multi-target interventions. TCM， through the comprehensive effects of multiple components and targets， is better suited to address the complex pathological features of VaD. However， current research on TCM for VaD still has limitations， including incompletely clarified mechanisms and insufficient clinical studies. Therefore， future research should further integrate multidisciplinary approaches， such as modern pharmacology and molecular biology， to deeply explore TCM resources and investigate diverse interdisciplinary collaborative treatment models， providing new ideas and strategies for VaD therapy.

Olfactory receptors (ORs) form the largest superfamily of G protein-coupled receptors (GPCRs). Traditionally recognized for their role in the nasal olfactory epithelium, where they mediate the sense of smell, accumulating evidence has firmly established their ectopic expression in non-olfactory tissues, including the intestine, lungs, and kidneys. The intestine, as the primary site for nutrient digestion and absorption, harbors a highly complex chemical environment. To adapt to this environment, the gut employs a sophisticated network of “chemosensors” to monitor luminal contents and maintain homeostasis. Among these sensors, intestinal ORs have emerged as crucial functional components, serving as a molecular bridge that connects environmental chemical signals—such as food-derived odorants—to specific physiological responses. This discovery has significantly deepened our understanding of how dietary flavors and compounds influence intestinal physiology at the molecular level. This review systematically summarizes the expression profiles, ligand classification, and biological functions of ORs within the gastrointestinal tract. Studies indicate that intestinal ORs exhibit distinct spatial distribution patterns across different gut segments and display cell-type specificity, particularly within enterocytes and enteroendocrine cells. These receptors function as versatile sensors capable of recognizing a wide variety of ligands, including exogenous dietary components, gut microbiota metabolites such as short-chain fatty acids, and endogenous small molecules like azelaic acid. Upon activation by specific ligands, intestinal ORs trigger intracellular signaling cascades, primarily involving the AC-cAMP-PKA pathway or calcium influx channels. A major focus of this review is to elucidate the molecular mechanisms by which these receptors regulate the secretion of gut hormones. Activation of specific ORs in enteroendocrine cells has been shown to stimulate the release of hormones such as glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and serotonin (5-HT), thereby modulating systemic energy metabolism, glucose homeostasis, and gastrointestinal motility. Furthermore, the review addresses the critical roles of ORs in immune regulation and pathology. Evidence suggests that specific ORs contribute to the maintenance of intestinal immune homeostasis and may offer protection against inflammation. Beyond their involvement in inflammatory responses, ORs such as Olfr78 have been shown to regulate the differentiation and function of intestinal endocrine cells. Similarly, Olfr544 has been demonstrated to alleviate intestinal inflammation by remodeling the gut microbiome and metabolome. These findings collectively suggest that specific ORs hold promise as therapeutic targets for mitigating intestinal inflammation and maintaining gut homeostasis. Additionally, the review explores the emerging role of ORs in cancer. Although OR expression is often downregulated in tumor tissues compared to normal mucosa, activation of specific ORs by certain ligands can inhibit tumor cell proliferation and migration and induce apoptosis via pathways such as MEK/ERK and p38 MAPK. Conversely, other receptors, such as OR7C1, may serve as biomarkers for cancer-initiating cells. In conclusion, intestinal ORs represent a vital component of the gut’s sensory network. The review also discusses the translational potential of these findings. By elucidating the precise pairing relationships between dietary components and specific ORs, novel therapeutic strategies could be developed. Intestinal ORs may thus emerge as promising targets for nutritional and pharmacological interventions in metabolic diseases, inflammatory bowel diseases, and malignancies.

OBJECTIVES: To investigate the role and mechanism of Brahma-related gene 1 (Brg1) in regulating the Wnt/β-catenin signaling pathway in a bronchopulmonary dysplasia (BPD) model. METHODS: Wild-type C57BL/6 and Brg1^f1/f1 mice were randomly divided into four groups: wild-type control, wild-type BPD, Brg1^f1/f1 control, and Brg1^f1/f1 BPD (n=5 each). Immortalized mouse pulmonary alveolar type 2 cells (imPAC2) were cultured, and Brg1 gene was knocked down using lentivirus transfection technology. Cells were divided into three groups: control, empty vector, and Brg1 knockdown. Hematoxylin and eosin staining and immunofluorescence were used to detect pathological changes in mouse lung tissue. Western blot and real-time fluorescent quantitative PCR were used to measure Brg1 protein and mRNA expression levels in mouse lung tissue. Western blot and immunofluorescence were used to detect the expression of homeodomain-containing protein homeobox (HOPX), surfactant protein C (SPC), and Wnt/β-catenin signaling pathway proteins in mouse lung tissue and imPAC2 cells. The CCK8 assay was used to assess the proliferation of imPAC2 cells, and co-immunoprecipitation was performed to verify the interaction between Brg1 and β-catenin proteins in imPAC2 cells. RESULTS: Compared to the Brg1^f1/f1 control group and wild-type BPD group, the Brg1^f1/f1 BPD group showed increased alveolar diameter and SPC protein expression, and decreased relative density of pulmonary vasculature and HOPX protein expression (P<0.05). Compared to the control group, the Brg1 knockdown group showed increased cell proliferation ability, protein expression levels of SPC, Wnt5a and β-catenin, and β-catenin protein fluorescence intensity, along with decreased HOPX protein expression (P<0.05). An interaction between Brg1 and β-catenin proteins was confirmed. CONCLUSIONS The Brg1 gene may promote the proliferation of alveolar type 2 epithelial cells by regulating the Wnt/β-catenin signaling pathway, thus influencing the occurrence and development of BPD.
Animals ; DNA Helicases/genetics* ; Transcription Factors/genetics* ; Wnt Signaling Pathway/physiology* ; Nuclear Proteins/genetics* ; Mice ; Bronchopulmonary Dysplasia/etiology* ; Mice, Inbred C57BL ; beta Catenin/physiology* ; Disease Models, Animal ; Cell Proliferation ; Lung/pathology* ; Male

OBJECTIVES: Osteoarthritis (OA) is one of the most common chronic degenerative diseases, with chondrocyte apoptosis and extracellular matrix (ECM) degradation as the major pathological changes. The mechanical stimulation can attenuate chondrocyte apoptosis and promote ECM synthesis, but the underlying molecular mechanisms remain unclear. This study aims to investigate the role of primary cilia (PC) in mediating the effects of mechanical stimulation on OA progression. METHODS: In vivo, conditional knockout mice lacking intraflagellar transport 88 (IFT88^flox/flox IFT88 knockout; i.e., primary cilia-deficient mice) were generated, with wild-type mice as controls. OA models were established via anterior cruciate ligament transection combined with destabilization of the medial meniscus, followed by treadmill exercise intervention. OA progression was evaluated by hematoxylin-eosin staining, safranin O-fast green staining, and immunohistochemistry; apoptosis was assessed by TUNEL staining; and limb function by rotarod testing. In vitro, primary articular chondrocytes were isolated from mice and transfected with lentiviral vectors to suppress IFT88 expression, thereby constructing a primary cilia-deficient cell model. Interleukin-1β (IL-1β) was used to induce an inflammatory environment, while cyclic tensile strain (CTS) was applied via a cell stretcher to mimic mechanical loading on chondrocytes. Immunofluorescence and Western blotting were used to detect the protein expression levels of type II collagen α1 chain (COL2A1), primary cilia, IFT88, and caspase-12; reverse transcription polymerase chain reaction was performed to assess COL2A1 mRNA levels; and flow cytometry was used to evaluate apoptosis. RESULTS: In vivo, treadmill exercise significantly reduced Osteoarthritis Research Society International (OARSI) scores and apoptotic cell rates, and improved balance ability in wild-type OA mice, whereas IFT88-deficient OA mice showed no significant improvement. In vitro, CTS inhibited IL-1β-induced ECM degradation and apoptosis in primary chondrocytes; however, this protective effect was abolished in cells with suppressed primary cilia expression. CONCLUSIONS Mechanical stimulation delays OA progression by mediating signal transduction through primary cilia, thereby inhibiting cartilage degeneration and chondrocyte apoptosis.
Animals ; Chondrocytes/cytology* ; Apoptosis/physiology* ; Mice ; Cilia/metabolism* ; Osteoarthritis/pathology* ; Extracellular Matrix/metabolism* ; Mice, Knockout ; Disease Progression ; Interleukin-1beta ; Male ; Cells, Cultured

Stem cells play a crucial role in maintaining tissue regenerative capacity and homeostasis. However, mechanisms associated with stem cell senescence require further investigation. In this study, we conducted a proteomic analysis of human dental pulp stem cells (HDPSCs) obtained from individuals of various ages. Our findings showed that the expression of NUP62 was decreased in aged HDPSCs. We discovered that NUP62 alleviated senescence-associated phenotypes and enhanced differentiation potential both in vitro and in vivo. Conversely, the knocking down of NUP62 expression aggravated the senescence-associated phenotypes and impaired the proliferation and migration capacity of HDPSCs. Through RNA-sequence and decoding the epigenomic landscapes remodeled induced by NUP62 overexpression, we found that NUP62 helps alleviate senescence in HDPSCs by enhancing the nuclear transport of the transcription factor E2F1. This, in turn, stimulates the transcription of the epigenetic enzyme NSD2. Finally, the overexpression of NUP62 influences the H3K36me2 and H3K36me3 modifications of anti-aging genes (HMGA1, HMGA2, and SIRT6). Our results demonstrated that NUP62 regulates the fate of HDPSCs via NSD2-dependent epigenetic reprogramming.
Humans ; Dental Pulp/cytology* ; Nuclear Pore Complex Proteins/genetics* ; Cellular Senescence/genetics* ; Stem Cells/metabolism* ; Epigenesis, Genetic ; Cell Proliferation ; Cell Differentiation ; Histone-Lysine N-Methyltransferase/metabolism* ; Cells, Cultured ; Cellular Reprogramming ; Cell Movement ; Proteomics

Objective To investigate the value of the maximum standard uptake value(SUVmax)obtained with orbital SEPCT/CT for evaluating activity of thyroid-associated ophthalmopathy(TAO)and predicting curative efficacy.Methods A total of 96 patients with initially diagnosed TAO were retrospectively collected,including 71 with clinical activity score(CAS)≥3(active group)and 25 with CAS=2(inactive group).Data of orbital SEPCT/CT were collected,and the patients were treated with hormones or immunosuppressants for 3 months.CAS was performed again within 1 week after treatment,and orbital imaging was reviewed.The patients were divided into effective group and ineffective group according to treatment results.Pretreatment(pre)SUVmax(pre-SUVmax)and imaging agent uptake rate(UR)(pre-UR)in extraocular muscle were compared between active and inactive groups.Pre-CAS,post-treatment(post)CAS(post-CAS),as well as pre-SUVmax,post-SUVmax,pre-UR,post-UR and the difference of pre-and post-treatment CAS,SUVmax and UR(△CAS,△UR,△SUVmax)of extraocular muscle were compared between effective group and ineffective group.The correlations of SUVmax,UR and CAS were analyzed.Pre-CAS,pre-SUVmax and pre-UR were included in univariate and multivariate logistic regression analysis to screen the predictors of effective treatment of TAO.Results Pre-SUVmax and pre-UR of extraocular muscle in active group were higher than those in inactive group(both P＜0.05).Among 96 cases,70 were in effective group and 26 were in ineffective group.Pre-CAS,the proportion of pre-CAS≥3 scores,pre-SUVmax,pre-UR,△CAS,△SUVmax and △UR in effective group were all higher than those in ineffective group(all P＜0.05).Pre-SUVmax and pre-UR in extraocular muscle of TAO patients were positively correlated with pre-CAS(rs=0.419,0.395,both P＜0.001),while post-SUVmax and post-UR were positively correlated with post-CAS(rs=0.322,0.221,P=0.001,0.030),△SUVmax and △UR were positively correlated with △CAS(rs=0.368,0.206,P＜0.001,P=0.044).Pre-CAS≥3(OR=2.95)and pre-SUVmax(OR=4.22)were both independent predictors of effective treatment of TAO(both P＜0.05).Conclusion SUVmax obtained with orbital SEPCT/CT could be used to quantitatively assess TAO activity and predict curative efficacy.

Objective This study applies Roy adaptation theory to deeply explore the experience of food avoid-ance behavior in patients with inflammatory bowel disease(IBD),offering insights for developing dietary management strategies.Methods A descriptive qualitative research method was employed.By purposive sampling,24 IBD pa-tients hospitalized in the gastroenterology department of a tertiary hospital in Nanjing from July 2022 to December 2024 were selected for semi-structured interviews.Data were analyzed using a directed content analysis approach.Results This study identified 4 main themes and 11 sub-themes,encompassing overattribution leading to inappro-priate avoidance(recurrent symptoms triggering overattribution,disease staging triggering inappropriate avoidance),negative self-perception leading management struggles(illness fear diminishing self-efficacy,disease trauma eroding self-identity,knowledge deficiency constraining self-determination),functional impairment intensifying role challenges(role internalization undermining social function,social roles relinquishing dietary management),and external con-straints amplifying practical difficulties(family and friend oversight heightening dietary stress,healthcare gaps foster-ing practical helplessness,traditional beliefs restricting dietary exploration,economic hardship limiting balanced nu-trition).Conclusion The interplay of overattribution,negative self-perception,functional impairment,and external constraints in IBD patients hinders their ability to adapt to disease fluctuations,ensnaring them in the adaptive predicament of food avoidance behavior.Healthcare professionals should comprehensively address these factors by fostering accurate perceptions,enhancing psychological support,guiding effective coping strategies,and optimizing ex-ternal resources,thereby improving patients' overall adaptive capacity and promoting their recovery.

Objective:To investigate the application and safety of cardiopulmonary bypass precharge with 4% succinylated gelatin during surgery for children with cyanotic congenital heart disease (CCHD).Methods:A prospective case-control study was conducted. One hundred and thirty children with CCHD undergoing cardiac surgery admitted to Shaanxi Provincial People's Hospital in 2021-2024 were selected as study participants. Participants were divided into control group ( n=65) and gelatin group ( n=65) by random number table method based on the principle of matching baseline characteristics between groups. Children in the control group were pre-filled with 10-20 ml/kg of fresh frozen plasma, while the gelatin group was pre-filled with 10-20 ml/kg of 4% succinyl gelatin. Thrombelastogram parameters [fibrin formation time, blood clot strength, fibrinogen maximum amplitude, fibrinogen content], hematological parameters [platelet count, prothrombin time (PT), prothrombin activity (PTA), hemoglobin], myocardial function [troponin, creatine kinase, creatine kinase isoenzyme (CK-MB)] and liver-kidney function were compared before and after treatment.Measurement data with normal distribution was expressed as " xˉ±s", independent sample t-test was used on comparison between groups, paired t-test was used for intra-group comparisons before and after treatment. Counting data was expressed as rate or composition ratio, χ2 test was used on comparison between groups. Results:Comparison between groups showed that before treatment, the difference of various thromboelastography parameters, haematological parameters, myocardial function indexes, liver and kidney function indexes were not statistically significant ( P>0.05). Compared to before treatment, R, PTA, troponin and creatine kinase increased in both groups after treatment [control group:(51±4) s vs. (43±3) s, (98±15)% vs. (95±12)%, (0.624±0.085) μg/L vs. (0.040±0.005) μg/L, (711±50) U/L vs. (96±11) U/L, (60±7) U/L vs. (22±4) U/L, t values were -17.92、-2.13、-104.63、-165.15、-57.43, respectively, all P<0.001; gelatin group: (51±4) s vs. (42±3) s, (100±16)% vs. (94±13)%, (0.631±0.113) μg/L vs. (0.041±0.004) μg/L, (717±52) U/L vs.(97±11) U/L, (62±7) U/L vs.(24±4) U/L, t values were -19.79、-3.09、-81.31、-157.70、-54.67, respectively, all P<0.001], while MA, MAf, FLEV, platelet count, PT and hemoglobin decreased [control group: (50±4) mmHg vs. (57±5) mmHg、(5.5±0.9) mmHg vs. (13.8±1.3) mmHg、(1.58±0.22) g/L vs.(2.64±0.31) g/L、(217±21)×10 9/L vs. (275±25)×10 9/L、(13.3±0.5) s vs.(14.7±0.8) s、(116±12) g/L vs.(127±17) g/L, t values were 14.79、61.26、32.25、20.58、17.21、6.09,respectively, all P<0.001; gelato group: (49±3) mmHg vs. (57±5) mmHg、(5.7±0.8) mmHg vs. (14.0±1.4) mmHg、(1.62±0.27) g/L vs.(2.59±0.26) g/L、(214±20)×10 9/L vs.(273±23)×10 9/L、(13.4±0.5) s vs.(14.7±0.8) s、(114±12) g/L vs.(128±17) g/L, t values were 16.34、62.05、29.51、22.77、14.91、7.41, respectively, all P<0.001], but the differences between groups were not statistically significant (all P>0.05). The difference of albumin, alanine aminotransferase, aspartate aminotransferase and creatinine before and after treatment were not statistically significant (all P>0.05). Conclusion:4% succinylated gelatin does not increase the risk of coagulation dysfunction during perioperative period in children with CCHD. It has small influence on liver-kidney function and has high safety.

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Surgical resection remains the preferred treatment modality, offering the potential for cure. However, over half of HCC patients present as intermediate to advanced stages at diagnosis, with multiple factors precluding surgical resection. Conversion therapy represents an important treatment strategy by enabling tumor downstaging, offering future resectability for patients with intermediate-to-advanced HCC who are initially unresectable. This article reviews the relevant concepts and research progress in conversion therapy for HCC.

ObjectiveStudies have shown that nuciferine has anti-cerebral ischemia effect， but the specific mechanism of action has not been elaborated. Based on the transcriptome results， the pharmacological mechanism of nuciferine against cerebral ischemia was analyzed from multiple dimensions including tissue， cell， pathological process， biological process and signaling pathway. MethodsThirty SD rats were randomly divided into the sham group， model group and nuciferine group（40 mg·kg^-1） according to weight. Except for the sham group， the model of middle cerebral artery occlusion（MCAO） was established by thread embolization method after 30 min of administration in the other two groups. Twenty-four hours after surgery， transcriptome sequencing was used to detect the gene expression profiles in the cortex penumbra of rat cerebral tissue， and gene ontology（GO） and kyoto encyclopedia of genes and genomes（KEGG） pathway enrichment analysis were performed for differentially expressed genes. The mechanismof nuciferine against cerebral ischemia was analyzed from 5 dimensions of tissue， cell， pathological process， biological process and signaling pathway by the transcriptome-based multi-scale network pharmacology platform（TMNP）. ResultsTranscriptome sequencing and gene quantitative analysis showed that 667 genes were significantly reversed by nuciferine. Further enrichment analysis of KEGG and GO suggested that the pathways of nuciferine involved regulating stress response， ion transport， cell proliferation and differentiation， and synaptic function. TMNP research found that at the tissue level， nuciferine could significantly improve the cerebral tissue injury caused by ischemia. At the cellular and pathological levels， nuciferine could play an anti-cerebral ischemia role by improving the state of various nerve cells， mobilizing immune cells， regulating inflammation. And at the level of biological processes and signaling pathways， nuciferine mainly acted on the processes such as vascular remodeling， inflammation-related signaling pathways， and synaptic signaling. ConclusionCombined with the results of transcriptome sequencing， gene quantitative analysis and TMNP， the mechanism of nuciferine against cerebral ischemia may be related to processes such as intervening in stress response and inflammation， affecting vascular remodeling and regulating synaptic function. These results can provide a basis and reference for further study of the pharmacological mechanism of nuciferine against cerebral ischemia.