1.Targeted therapeutic strategies for infectious pneumonia:immunocyte-derived biomimetic nano-drug delivery systems
Hao TIAN ; Qi BA ; Wei GONG ; Yuli WANG ; Yang YANG ; Chunsheng GAO ; Meiyan YANG
Military Medical Sciences 2025;49(8):617-623
Infectious pneumonia caused by bacteria,viruses,or other pathogenic microorganisms remains a huge threat to human health.Immunocyte-derived biomimetic nano-drug delivery systems can be used for drug delivery by taking advantage of the natural anti-inflammatory effect of immune cells and thus show great potential in lung-targeted therapy.This review begins by introducing different types of immune cells in the lung.The preparation methods of immunocyte-derived biomimetic nano-drug delivery systems and their applications in bacterial pneumonia,viral pneumonia,acute respiratory distress syndrome and cytokine storms are also reviewed.The review is expected to provide data for the targeted therapy of infectious pneumonia.
2.Value of combined prediction of peripheral blood CD4+,CD3-CD16+CD56+,CD8+,CD19+for survival outcome in patients with EBV infection-associated hemophagocytic syndrome
Zhe PENG ; Pei XING ; Chenlu WANG ; Wenjie YU ; Yuli JIA
International Journal of Laboratory Medicine 2025;46(8):982-986,991
Objective To analyze the value of combined prediction of peripheral blood CD4+,CD3-CD16+CD56+,CD8+,CD19+for the risk of death in patients with Epstein-Barr virus-associated hemophagocytic syn-drome(EBV-HLH).Methods A total of 84 patients with EBV-HLH who were treated in Beijing Friendship Hospital Affiliated to Capital Medical University and Peking University First Hospital from May 2021 to A-pril 2023 were selected and divided into a death group(17 cases)and a survival group(67 cases)according to their survival outcomes within 6 months.The general information and peripheral blood T lymphocyte subsets of the two groups were compared,multivariate Logistic regression analysis was conducted to investigate the influencing factors of death in EBV-HLH patients,and receiver operating characteristic(ROC)curve was used to evaluate the predictive value of peripheral blood T lymphocyte subsets on death in EBV-HLH patients.Results The platelet count,hemoglobin,CD4+and CD3-CD16+CD56+levels in the death group were lower than those in the survival group,while the levels of CD8+and CD19+were higher than those in the survival group(P<0.05).Multivariate Logistic regression analysis showed that platelet count,hemoglobin,CD4+,and CD3-CD16+CD56+were all independent protective factors for the death of EBV-HLH patients,while CD8+and CD19+were independent risk factors for the death of EBV-HLH patients(P<0.05).The ROC curve results showed that the area under the curve of combined prediction of CD4+,CD8+,CD19+,CD3 CD16+CD56+for death in EBV-HLH patients was 0.923,with sensitivity and specificity of 94.12%and 80.60%,respectively,which were significantly higher than those predicted by each individual indicator(P<0.05).Conclusion The abnormal expression of CD4+,CD3-CD16+CD56+,CD8+,and CD19+in peripheral blood of EBV-HLH patients is associated with their survival outcomes,and the combined prediction of CD4+,CD3-CD16+CD56+,CD8+,and CD19+has high reference value for predicting patients'death.
3.Establishment and evaluation of a combination of disease and syndrome model of post-stroke depression based on the theory of"disease-syndrome-drug"
Zhiheng LIU ; Yuli CHEN ; Yu LIU ; Xin WANG ; Yu LIU ; Lin LIU
Acta Laboratorium Animalis Scientia Sinica 2025;33(3):388-398
Objective To construct an animal model of post-stroke depression(PSD)based on the theory of"depression,stasis,phlegm",with the aim of developing and validating an objective assessment system.Methods Rats were divided randomly into five groups:control,depression,stroke,PSD,and Baishile decoction groups.A PSD syndrome-based animal model was established in rats using a combination of middle cerebral artery occlusion(MCAO)and chronic unpredictable mild stress(CUMS)."Depression,stasis,phlegm"were then evaluated in the model rats using the Morris water maze,open field,forced swimming,and sucrose preference tests,and by detection of neurotransmitter levels,brain tissue pathology,tongue and forepaw color RGB values,and blood rheology.Results PSD rats exhibited significantly shorter target quadrant dwelling times,platform crossings,and climbing and rearing frequencies,a significantly lower sucrose preference,and a significantly higher immobility time in the forced swim test compared with control rats.Hematoxylin and eosin and Nissl staining revealed brain tissue damage in PSD rats.Serum and cerebrospinal fluid levels of 5-hydroxytryptamine(5-HT)were significantly decreased,glutamate levels were significantly increased,and tongue and forepaw RGB values were all decreased.Blood rheology showed a hypercoagulable state and blood lipid metabolism-related indicators were significantly abnormal.Rats in the Baishile decoction group showed significant improvements compared with the PSD group,including increased target quadrant dwelling times,number of platform crossings,and climbing and rearing frequencies,increased sucrose preference,decreased immobility time in the forced swim test,improved brain tissue pathology,increased serum and cerebrospinal fluid levels of 5-HT,decreased glutamate levels,increased tongue and claw RGB values,and varying degrees of improvement in blood rheology and blood lipid metabolism-related indicators.Conclusions The combination of MCAO and CUMS successfully established a syndrome-based animal model of PSD exhibiting the characteristics of"depression,stasis,phlegm",with corresponding objective assessment criteria.
4.Circadian genes CLOCK and BMAL1 in cancer: mechanistic insights and therapeutic strategies.
Yuli SHEN ; Yuqian ZHAO ; Xue SUN ; Guimei JI ; Daqian XU ; Zheng WANG
Journal of Zhejiang University. Science. B 2025;26(10):935-948
The circadian clock is a highly conserved timekeeping system in organisms, which maintains physiological homeostasis by precisely regulating periodic fluctuations in gene expression. Substantial clinical and experimental evidence has established a close association between circadian rhythm disruption and the development of various malignancies. Research has revealed characteristic alterations in the circadian gene expression profiles in tumor tissues, primarily manifested as a dysfunction of core clock components (particularly circadian locomotor output cycles kaput (CLOCK) and brain and muscle ARNT-like 1 (BMAL1)) and the widespread dysregulation of their downstream target genes. Notably, CLOCK demonstrates non-canonical oncogenic functions, including epigenetic regulation via histone acetyltransferase activity and the circadian-independent modulation of cancer pathways. This review systematically elaborates on the oncogenic mechanisms mediated by CLOCK/BMAL1, encompassing multidimensional effects such as cell cycle control, DNA damage response, metabolic reprogramming, and tumor microenvironment (TME) remodeling. Regarding the therapeutic strategies, we focus on cutting-edge approaches such as chrononutritional interventions, chronopharmacological modulation, and treatment regimen optimization, along with a discussion of future perspectives. The research breakthroughs highlighted in this work not only deepen our understanding of the crucial role of circadian regulation in cancer biology but also provide novel insights for the development of chronotherapeutic oncology, particularly through targeting the non-canonical functions of circadian proteins to develop innovative anti-cancer strategies.
Humans
;
ARNTL Transcription Factors/physiology*
;
Neoplasms/therapy*
;
CLOCK Proteins/physiology*
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Circadian Clocks/genetics*
;
Animals
;
Circadian Rhythm/genetics*
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Tumor Microenvironment
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Epigenesis, Genetic
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Gene Expression Regulation, Neoplastic
5.Local abaloparatide administration promotes in situ alveolar bone augmentation via FAK-mediated periosteal osteogenesis.
Ruyi WANG ; Yuan LI ; Bowen TAN ; Shijia LI ; Yanting WU ; Yao CHEN ; Yuran QIAN ; Haochen WANG ; Bo LI ; Zhihe ZHAO ; Quan YUAN ; Yu LI
International Journal of Oral Science 2025;17(1):63-63
Insufficient alveolar bone thickness increases the risk of periodontal dehiscence and fenestration, especially in orthodontic tooth movement. Abaloparatide (ABL), a synthetic analog of human PTHrP (1-34) and a clinical medication for treating osteoporosis, has recently demonstrated its potential in enhancing craniofacial bone formation. Herein, we show that intraoral submucosal injection of ABL, when combined with mechanical force, promotes in situ alveolar bone thickening. The newly formed bone is primarily located outside the original compact bone, implying its origin from the periosteum. RNA sequencing of the alveolar bone tissue revealed that the focal adhesion (FA) pathway potentially mediates this bioprocess. Local injection of ABL alone enhances cell proliferation, collagen synthesis, and phosphorylation of focal adhesion kinase (FAK) in the alveolar periosteum; when ABL is combined with mechanical force, the FAK expression is upregulated, in line with the accomplishment of the ossification. In vitro, ABL enhances proliferation, migration, and FAK phosphorylation in periosteal stem cells. Furthermore, the pro-osteogenic effects of ABL on alveolar bone are entirely blocked when FAK activity is inhibited by a specific inhibitor. In summary, abaloparatide combined with mechanical force promotes alveolar bone formation via FAK-mediated periosteal osteogenesis. Thus, we have introduced a promising therapeutic approach for drug-induced in situ alveolar bone augmentation, which may prevent or repair the detrimental periodontal dehiscence, holding significant potential in dentistry.
Osteogenesis/drug effects*
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Periosteum/cytology*
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Parathyroid Hormone-Related Protein/administration & dosage*
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Animals
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Focal Adhesion Protein-Tyrosine Kinases/metabolism*
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Alveolar Process/drug effects*
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Cell Proliferation/drug effects*
;
Phosphorylation
;
Rats
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Male
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Humans
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Focal Adhesion Kinase 1/metabolism*
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Cell Movement/drug effects*
6.Identification of Key Genes and Potential Therapeutic Drugs Associated with Microglial Senescence and Alzheimer's Disease Based on GEO Database Analysis
Shuo GAO ; Peichang WANG ; Yuli HOU
Journal of Modern Laboratory Medicine 2025;40(6):7-11,17
Objective To identify key genes and potential therapeutic drugs associated with Alzheimer's disease(AD)based on microglial senescence using bioinformatics analysis,providing new targets and insights for AD diagnosis and treatment.Methods Gene expression datasets related to microglial senescence and AD,specifically GSE62420 and GSE74615,were downloaded from the Gene Expression Omnibus(GEO)database.Differential Expressed Genes(DEGs)were identified using R software.Functional enrichment analysis,including gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis,was performed using the DAVID online tool.The STRING database was used to construct the protein-protein interaction(PPI)network,and the CytoHubba plugin in Cytoscape software was applied to identify hub genes.The differential expression of hub genes was validated using the GSE129296 and GSE208386 datasets.Potential therapeutic drugs targeting these genes were predicted using the DSigDB database.Results A total of 35 DEGs,including 34 upregulated and 1 downregulated gene,were identified from the intersection of the GSE74615 and GSE62420 datasets.GO and KEGG enrichment analyses indicated that these DEGs were significantly involved in gene expression regulation,protein binding,metal ion binding,and the hypoxia-inducible factor 1(HIF-1)signaling pathway.PPI network analysis and CytoHubba screening identified ten hub genes:HIF1A,secreted phosphoprotein 1(SPP1),integrin alpha X(ITGAX),triggering receptor expressed on myeloid cells(TREM2),glycoprotein non-metastatic melanoma protein B(GPNMB),anexelekto receptor tyrosine kinase(AXL),Cystatin F(CST7),interleukin-12B(IL12B)、lipoprteinlipase(LPL)and fatty acid-binding protein 5(FABP5).Validation using the GSE129296 dataset showed that HIF1A,SPP1,ITGAX,TREM2,GPNMB,AXL,CST7 and FABP5 were significantly upregulated in microglia of AD mice,and the differences were statistically significant(t=8.411~29.49,all P<0.05).Further validation using the GSE208386 dataset indicated that LPL,SPP1,AXL and CST7 were significantly upregulated during microglial senescence,and the differences were statistically significant(t=4.755~5.964,all P<0.05).Based on these validation results,SPP1,AXL and CST7 were identified as key genes in AD.Drug prediction analysis using DSigDB revealed that potential therapeutic compounds targeting these genes exhibit anti-aging,anti-tumor,anti-inflammatory and DNA damage repair effects.Conclusion The key genes SPP1,AXL and CST7,identified based on microglial senescence,may serve as potential biomarkers for AD.Furthermore,multiple potential therapeutic drugs were predicted,offering new targets and strategies for AD diagnosis and treatment.
7.A qualitative study on barriers to active management in elderly patients with chronic heart failure based on the Theoretical Domains Framework
Minghao QI ; Yu WANG ; Ke WANG ; Mengyu HE ; Yuli HUANG ; Feng WANG ; Jing ZHOU
Chinese Journal of Modern Nursing 2025;31(32):4354-4360
Objective:To gain an in-depth understanding of the barriers to active management in elderly patients with chronic heart failure (CHF) and to provide evidence for targeted interventions.Methods:A descriptive qualitative research method was adopted. Using purposive sampling, a total of 14 elderly CHF patients admitted to the Department of Cardiovascular Medicine, the First Affiliated Hospital of Bengbu Medical College, from January to February 2025 were selected as study participants. Based on the Theoretical Domains Framework (TDF), a semi-structured in-depth interview guide was developed. NVivo 12.0 software was used to organize and code the data, and directed content analysis was applied.Results:Eight TDF-related domains of barriers were identified and summarized into four themes: misconceptions of disease and information processing barriers (knowledge; memory, attention, and decision processes) ; dependence on family members and limited accessibility of medical resources (social influence; environmental context and resources) ; negative goal motivation and low management confidence (goals; beliefs about consequences and capabilities) ; and emotional management obstacles and fatigue from self-regulation (emotion) .Conclusions:On the basis of meeting elderly CHF patients' knowledge needs, healthcare professionals should expand their access to information, improve social support systems, stimulate intrinsic motivation and self-efficacy, and alleviate negative emotions and fatigue related to self-regulation, thereby enhancing the positivity of self-health management and achieving sustainability in health management.
8.Influence of Dapagliflozin on glucose metabolism and cardiac function in elderly patients with ST-segment elevation myocardial infarction complicated with type 2 diabetes mellitus after percutaneous coronary intervention
Yuli LU ; Jiandong XIAO ; Ya WANG
Chinese Journal of Diabetes 2025;33(8):577-581
Objective To analyze the influence of Dapagliflozin on ventricular remodeling,soluble suppression of tumorigenicity-2(sST2)and brain natriuretic peptide(BNP)in patients with elderly ST-segment elevation myocardial infarction(STEMI)complicated with type 2 diabetes mellitus(T2DM)after percutaneous coronary intervention(PCI).Methods From April 2021 to March 2023,118 elderly patients with STEMI complicated with T2DM treated by PCI were selected from People's Hospital of Hengshui.They were divided into conventional hypoglycemic therapy control(Con,n=59)group and conventional hypoglycemic therapy combined with Dapagliflozin(Dap,n=59)group according to the treatment strategy.All the participants were treated for 24 weeks.The general data,biochemical indexes,BNP,N-terminal pro-B-type natriuretic peptide(NT-proBNP),soluble growth stimulating expression factor 2(sST2)and lipoprotein-associated phospholipase A2(LP-PLA2),left ventricular ejection fraction(LVEF),left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),and left ventricular mass index(LVMI)were compared between the two groups.Results After 24 weeks of treatment,the BNP,NT-proBNP,fasting plasma glucose(FPG),2 h postprandial blood glucose(2 hPG),glycosylated hemoglobin(HbA1c),LVEDD,LVESD,LVMI,serum sST2 and LP-PLA2 were lower in Dap group than in Con group(P<0.05),while the LVEF was higher in Dap group than in Con group(P<0.05).The total incidence rate of major adverse cardiovascular events was significantly lower in Dap group than in Con group(P<0.05).The incidence rates of adverse drug reactions were 6.78%and 5.08%in the two groups respectively(P>0.05).Conclusions Dapagliflozin can improve the cardiac function and glucose metabolism status in elderly patients with STEMI and T2DM after PCI,and alleviate the ventricular remodeling,with good safety.
9.Vitamin D supplementation inhibits atherosclerosis through repressing macrophage-induced inflammation via SIRT1/mTORC2 signaling.
Yuli WANG ; Qihong NI ; Yongjie YAO ; Shu LU ; Haozhe QI ; Weilun WANG ; Shuofei YANG ; Jiaquan CHEN ; Lei LYU ; Yiping ZHAO ; Meng YE ; Guanhua XUE ; Lan ZHANG ; Xiangjiang GUO ; Yinan LI
Chinese Medical Journal 2025;138(21):2841-2843
10.A qualitative study on barriers to active management in elderly patients with chronic heart failure based on the Theoretical Domains Framework
Minghao QI ; Yu WANG ; Ke WANG ; Mengyu HE ; Yuli HUANG ; Feng WANG ; Jing ZHOU
Chinese Journal of Modern Nursing 2025;31(32):4354-4360
Objective:To gain an in-depth understanding of the barriers to active management in elderly patients with chronic heart failure (CHF) and to provide evidence for targeted interventions.Methods:A descriptive qualitative research method was adopted. Using purposive sampling, a total of 14 elderly CHF patients admitted to the Department of Cardiovascular Medicine, the First Affiliated Hospital of Bengbu Medical College, from January to February 2025 were selected as study participants. Based on the Theoretical Domains Framework (TDF), a semi-structured in-depth interview guide was developed. NVivo 12.0 software was used to organize and code the data, and directed content analysis was applied.Results:Eight TDF-related domains of barriers were identified and summarized into four themes: misconceptions of disease and information processing barriers (knowledge; memory, attention, and decision processes) ; dependence on family members and limited accessibility of medical resources (social influence; environmental context and resources) ; negative goal motivation and low management confidence (goals; beliefs about consequences and capabilities) ; and emotional management obstacles and fatigue from self-regulation (emotion) .Conclusions:On the basis of meeting elderly CHF patients' knowledge needs, healthcare professionals should expand their access to information, improve social support systems, stimulate intrinsic motivation and self-efficacy, and alleviate negative emotions and fatigue related to self-regulation, thereby enhancing the positivity of self-health management and achieving sustainability in health management.

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