1.Engineered plant extracellular vesicles: Emerging nanoplatforms for combinational cancer immunotherapy.
Fucai CHEN ; Rongrong BAO ; Wanyi YANG ; Yijing LU ; Jiaxin GUO ; Wenjing CHEN ; Jiale LI ; Kuanhan FENG ; Wen ZHANG ; Liuqing DI ; Liang FENG ; Ruoning WANG
Acta Pharmaceutica Sinica B 2025;15(11):5663-5701
Plant-derived extracellular vesicles (PDEVs), describe a group of nanoparticles released by plants. These particles are characterized by a lipid bilayer structure containing various proteins, lipids, nucleic acids, and unique metabolites. Although the study on PDEVs is relatively new, having only been around for ten years, they have shown promising development prospects in both basic research and clinical transformation areas. Evidence suggests that PDEVs have excellent application prospects in regulating inflammation and treating tumors. Their distinctive, vesicle-mimicking architecture and stellar biocompatibility render them prime candidates for ferrying various anti-cancer agents, including RNA, proteins, and conventional chemotherapy drugs. Increasingly, studies have shown that PDEVs can be engineered as an innovative platform for combination cancer immunotherapy. Consequently, this paper provides an extensive summary of current developments in engineering methods and strategies for PDEVs in cancer treatment and combined cancer immune therapeutics. The essential characteristics of PDEVs, including the biogenesis process and components, as well as their anti-tumor activity and mechanism, are summarized. Finally, the in vivo safety of PDEVs as delivery vectors and the challenges of scale-up production and clinical transformation are discussed.
2.Influencing factors of responsive caregiving among infant mothers in Weifang City
Ziyuan FU ; Fei YANG ; Mo ZHOU ; Xinxuan LI ; Ruoning WANG ; Ningxuan CUI ; Jing HUANG ; Yixin ZHANG ; Huafang JIANG ; Yuhua GUO ; Hong ZHOU
Journal of Peking University(Health Sciences) 2025;57(3):481-486
Objective:To describe the current status of responsive caregiving behavior of infant mothers,to analyze their influencing factors and pathways using the information-motivation-behavioral skills(IMB)model,and to provide a basis for further interventions related to responsive caregiving be-haviors and comprehensive promotion of early childhood development.Methods:This study was a cross-sectional survey using convenience sampling.Questionnaires were used to collect basic information about mothers and their infants,as well as data on mothers' responsive caregiving behavior,knowledge of re-sponsive caregiving,social support,and parenting self-efficacy.Multivariate linear regression models were employed to analyze the influencing factors of responsive caregiving behavior,and structural equa-tion modeling was used to analyze the pathways of these influencing factors.The criterion for inadequate responsive caregiving is defined as scores not exceeding the lower quartile(P25)of the total score.Results:Among 510 mothers of aged 0-12 months infants in Weifang City,the average score for respon-sive caregiving behavior was 16.41±3.99.The proportion of inadequate responsive caregiving was 25.7%.Mothers in the insufficient responsive caregiving group had lower scores in knowledge(7.70±1.41),social support(57.92±15.16),and parenting self-efficacy(30.36±6.48)compared with those in the sufficient group,with statistically significant differences(P<0.001).Logistic regres-sion analysis indicated that the influencing factors for responsive caregiving included the level of know-ledge about responsive parenting[adjusted OR(aOR)=0.795,95%CI:0.566-0.838],social support(aOR=0.979,95%CI:0.961-0.996),and parenting self-efficacy(aOR=0.894,95%CI:0.857-0.932).Structural equation modeling revealed that knowledge of responsive caregiving(β=0.089,P=0.031),social support(β=0.153,P=0.001),and parenting self-efficacy(β=0.296,P<0.001)were directly related to responsive caregiving behavior.Additionally,knowledge of responsive caregiving indirectly affected responsive caregiving behavior through parenting self-efficacy(β=0.095,P=0.014),and social support indirectly affected responsive caregiving behavior through parenting self-efficacy(β=0.497,P<0.001).Conclusion:The current level of responsive caregiving behavior among mothers of 0-1-year-old infants in Weifang City is not satisfactory.Future development of responsive care-giving interventions should focus on providing caregivers with relevant knowledge of responsive caregiving based on their needs.Additionally,it is essential to offer social support from multiple aspects to enhance caregivers' parenting self-efficacy,thereby promoting improvements in responsive caregiving behavior.
3.Association of white blood cell count with venous thromboembo-lism:a two-way Mendelian randomization study
Zhanli GUO ; Yuan WANG ; Lei ZHANG ; Jiayuan LI ; Ruoning LI ; Ying DONG ; Jianjun SUN
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(4):446-455
AIM:To explore the causal association between the counts of five types of white blood cells—neutrophils,monocytes,eosinophils,baso-phils,and lymphocytes—and venous thromboem-bolism(VTE).METHODS:Mendelian randomization(MR)analysis method was used,with genetic vari-ants associated with the five types of white blood cells as instrumental variables,and venous throm-boembolism occurrence risk as the outcome vari-able,inverse variance-weighted(IVW)method was employed as the primary analysis method,with MR-Egger regression,weighted median(WM),sim-ple model,and weighted mode methods used as supplements,to analyze the causal association be-tween the counts of five types of white blood cells and VTE,followed by reverse MR analysis.RE-SULTS:Neutrophil and lymphocyte counts are caus-ally associated with the risk of VTE.For neutrophil count,the IVW estimate(OR=0.867,95%CI:0.761-0.981,P=0.031),MR-Egger estimate(OR=0.754,95%CI:0.571-0.996,P=0.048),weighted median es-timate(OR=0.846,95%CI:0.729-0.981,P=0.027),and weighted model estimate(OR=0.748,95%CI:0.595-0.942,P=0.014)were calculated.For lympho-cyte count,the IVW estimate(OR=0.838,95%CI:0.741-0.949,P=0.005)and weighted median esti-mate(OR=0.024,95%CI:0.718-0.977,P=0.024)were calculated.Reverse MR analysis showed a causal association between the risk of VTE and neu-trophil count,the IVW estimate(OR=0.989,95%CI:0.980-0.999,P=0.024).CONCLUSION:Neutrophil and lymphocyte counts are related to the risk of VTE,and decrease in neutrophil and lymphocyte numbers may increase the risk of VTE.VTE occur-rence risk is associated with neutrophil count,and reducing the risk of VTE occurrence may increase neutrophil count.Further research is needed to un-derstand the underlying biological mechanisms be-hind this relationship.
4.Molecular mechanism of allicin-targeted regulation of epidermal growth factor receptor and kynureninase in the treatment of rheumatoid arthritis
Liang XU ; GULIMILA·MUHETAER ; Bowei JU ; Ruoning LI
Chinese Journal of Tissue Engineering Research 2025;29(20):4205-4214
BACKGROUND:Allicin,the main active ingredient in garlic,has anti-inflammatory and antioxidant effects,but the role and mechanism of allicin in ameliorating rheumatoid arthritis remain unclear.OBJECTIVE:To analyze differentially expressed genes in rheumatoid arthritis using gene expression data and explore the regulatory role of alliin in rheumatoid arthritis.METHODS:Gene expression data for rheumatoid arthritis were collected from the GSE45291 and GSE93777 datasets,and differential expression analysis was then performed.Co-expression network analysis was conducted on the common differentially expressed genes identified in both datasets to identify the module genes most closely related to rheumatoid arthritis,followed by functional enrichment analysis.The SwissTargetPrediction database was used to predict the target genes of allicin in the differentially expressed genes.The area under the receiver operator characteristic curve(AUC)of the differentially expressed target genes was calculated.Human immortalized rheumatoid arthritis fibroblast-like synoviocytes were seeded onto pore plates and cultured for 24 hours,and the cells were then divided into five groups.The control group was not treated;methotrexate was added to the positive drug group;and 20,80,and 160 μg/mL allicin was added to the low-,medium-,and high-dose allicin groups,respectively.After 48 hours of treatment,cell activity was assessed using cell counting kit-8 assay and cell apoptosis was detected using TUNEL assay.Levels of oxidative stress and inflammatory factors were measured by ELISA.Changes in mitochondrial membrane potential were detected by JC-1 staining.The expression levels of target genes and related signaling pathways were detected by RT-qPCR and western blot.RESULTS AND CONCLUSION:A total of 6 487 common differentially expressed genes were identified in the GSE45291 and GSE93777 datasets,and 12 co-expression modules were obtained.The magenta module had the highest correlation with rheumatoid arthritis,with module genes primarily enriched in the phosphatidylinositol 3-kinase/protein kinase B signaling pathway.Database predictions revealed that seven differentially expressed genes were targeted by allicin,with epidermal growth factor receptor having the highest AUC value in the GSE45291 dataset and kynureninase having the highest AUC value in the GSE93777 dataset.Treatment of human immortalized rheumatoid arthritis fibroblast-like synoviocytes with allicin significantly inhibited cell activity,promoted cell apoptosis,decreased the levels of reactive oxygen species,malondialdehyde,interleukin-6,interleukin-1β,increased the expression of mitochondrial membrane potential,decreased the mRNA and protein expression of epidermal growth factor receptor,kynureninase,mitochondrial dynamin-related protein 1,elevated the mRNA and protein expression of mitochondrial fusion protein 2,and increased the protein expression of p-AKT and p-PI3K.To conclude,allicin plays the potential therapeutic effects on rheumatoid arthritis through the regulation of target genes such as epidermal growth factor receptor and kynureninase.
5.Association of white blood cell count with venous thromboembo-lism:a two-way Mendelian randomization study
Zhanli GUO ; Yuan WANG ; Lei ZHANG ; Jiayuan LI ; Ruoning LI ; Ying DONG ; Jianjun SUN
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(4):446-455
AIM:To explore the causal association between the counts of five types of white blood cells—neutrophils,monocytes,eosinophils,baso-phils,and lymphocytes—and venous thromboem-bolism(VTE).METHODS:Mendelian randomization(MR)analysis method was used,with genetic vari-ants associated with the five types of white blood cells as instrumental variables,and venous throm-boembolism occurrence risk as the outcome vari-able,inverse variance-weighted(IVW)method was employed as the primary analysis method,with MR-Egger regression,weighted median(WM),sim-ple model,and weighted mode methods used as supplements,to analyze the causal association be-tween the counts of five types of white blood cells and VTE,followed by reverse MR analysis.RE-SULTS:Neutrophil and lymphocyte counts are caus-ally associated with the risk of VTE.For neutrophil count,the IVW estimate(OR=0.867,95%CI:0.761-0.981,P=0.031),MR-Egger estimate(OR=0.754,95%CI:0.571-0.996,P=0.048),weighted median es-timate(OR=0.846,95%CI:0.729-0.981,P=0.027),and weighted model estimate(OR=0.748,95%CI:0.595-0.942,P=0.014)were calculated.For lympho-cyte count,the IVW estimate(OR=0.838,95%CI:0.741-0.949,P=0.005)and weighted median esti-mate(OR=0.024,95%CI:0.718-0.977,P=0.024)were calculated.Reverse MR analysis showed a causal association between the risk of VTE and neu-trophil count,the IVW estimate(OR=0.989,95%CI:0.980-0.999,P=0.024).CONCLUSION:Neutrophil and lymphocyte counts are related to the risk of VTE,and decrease in neutrophil and lymphocyte numbers may increase the risk of VTE.VTE occur-rence risk is associated with neutrophil count,and reducing the risk of VTE occurrence may increase neutrophil count.Further research is needed to un-derstand the underlying biological mechanisms be-hind this relationship.
6.Influencing factors of responsive caregiving among infant mothers in Weifang City
Ziyuan FU ; Fei YANG ; Mo ZHOU ; Xinxuan LI ; Ruoning WANG ; Ningxuan CUI ; Jing HUANG ; Yixin ZHANG ; Huafang JIANG ; Yuhua GUO ; Hong ZHOU
Journal of Peking University(Health Sciences) 2025;57(3):481-486
Objective:To describe the current status of responsive caregiving behavior of infant mothers,to analyze their influencing factors and pathways using the information-motivation-behavioral skills(IMB)model,and to provide a basis for further interventions related to responsive caregiving be-haviors and comprehensive promotion of early childhood development.Methods:This study was a cross-sectional survey using convenience sampling.Questionnaires were used to collect basic information about mothers and their infants,as well as data on mothers' responsive caregiving behavior,knowledge of re-sponsive caregiving,social support,and parenting self-efficacy.Multivariate linear regression models were employed to analyze the influencing factors of responsive caregiving behavior,and structural equa-tion modeling was used to analyze the pathways of these influencing factors.The criterion for inadequate responsive caregiving is defined as scores not exceeding the lower quartile(P25)of the total score.Results:Among 510 mothers of aged 0-12 months infants in Weifang City,the average score for respon-sive caregiving behavior was 16.41±3.99.The proportion of inadequate responsive caregiving was 25.7%.Mothers in the insufficient responsive caregiving group had lower scores in knowledge(7.70±1.41),social support(57.92±15.16),and parenting self-efficacy(30.36±6.48)compared with those in the sufficient group,with statistically significant differences(P<0.001).Logistic regres-sion analysis indicated that the influencing factors for responsive caregiving included the level of know-ledge about responsive parenting[adjusted OR(aOR)=0.795,95%CI:0.566-0.838],social support(aOR=0.979,95%CI:0.961-0.996),and parenting self-efficacy(aOR=0.894,95%CI:0.857-0.932).Structural equation modeling revealed that knowledge of responsive caregiving(β=0.089,P=0.031),social support(β=0.153,P=0.001),and parenting self-efficacy(β=0.296,P<0.001)were directly related to responsive caregiving behavior.Additionally,knowledge of responsive caregiving indirectly affected responsive caregiving behavior through parenting self-efficacy(β=0.095,P=0.014),and social support indirectly affected responsive caregiving behavior through parenting self-efficacy(β=0.497,P<0.001).Conclusion:The current level of responsive caregiving behavior among mothers of 0-1-year-old infants in Weifang City is not satisfactory.Future development of responsive care-giving interventions should focus on providing caregivers with relevant knowledge of responsive caregiving based on their needs.Additionally,it is essential to offer social support from multiple aspects to enhance caregivers' parenting self-efficacy,thereby promoting improvements in responsive caregiving behavior.
7.Molecular mechanism of allicin-targeted regulation of epidermal growth factor receptor and kynureninase in the treatment of rheumatoid arthritis
Liang XU ; GULIMILA·MUHETAER ; Bowei JU ; Ruoning LI
Chinese Journal of Tissue Engineering Research 2025;29(20):4205-4214
BACKGROUND:Allicin,the main active ingredient in garlic,has anti-inflammatory and antioxidant effects,but the role and mechanism of allicin in ameliorating rheumatoid arthritis remain unclear.OBJECTIVE:To analyze differentially expressed genes in rheumatoid arthritis using gene expression data and explore the regulatory role of alliin in rheumatoid arthritis.METHODS:Gene expression data for rheumatoid arthritis were collected from the GSE45291 and GSE93777 datasets,and differential expression analysis was then performed.Co-expression network analysis was conducted on the common differentially expressed genes identified in both datasets to identify the module genes most closely related to rheumatoid arthritis,followed by functional enrichment analysis.The SwissTargetPrediction database was used to predict the target genes of allicin in the differentially expressed genes.The area under the receiver operator characteristic curve(AUC)of the differentially expressed target genes was calculated.Human immortalized rheumatoid arthritis fibroblast-like synoviocytes were seeded onto pore plates and cultured for 24 hours,and the cells were then divided into five groups.The control group was not treated;methotrexate was added to the positive drug group;and 20,80,and 160 μg/mL allicin was added to the low-,medium-,and high-dose allicin groups,respectively.After 48 hours of treatment,cell activity was assessed using cell counting kit-8 assay and cell apoptosis was detected using TUNEL assay.Levels of oxidative stress and inflammatory factors were measured by ELISA.Changes in mitochondrial membrane potential were detected by JC-1 staining.The expression levels of target genes and related signaling pathways were detected by RT-qPCR and western blot.RESULTS AND CONCLUSION:A total of 6 487 common differentially expressed genes were identified in the GSE45291 and GSE93777 datasets,and 12 co-expression modules were obtained.The magenta module had the highest correlation with rheumatoid arthritis,with module genes primarily enriched in the phosphatidylinositol 3-kinase/protein kinase B signaling pathway.Database predictions revealed that seven differentially expressed genes were targeted by allicin,with epidermal growth factor receptor having the highest AUC value in the GSE45291 dataset and kynureninase having the highest AUC value in the GSE93777 dataset.Treatment of human immortalized rheumatoid arthritis fibroblast-like synoviocytes with allicin significantly inhibited cell activity,promoted cell apoptosis,decreased the levels of reactive oxygen species,malondialdehyde,interleukin-6,interleukin-1β,increased the expression of mitochondrial membrane potential,decreased the mRNA and protein expression of epidermal growth factor receptor,kynureninase,mitochondrial dynamin-related protein 1,elevated the mRNA and protein expression of mitochondrial fusion protein 2,and increased the protein expression of p-AKT and p-PI3K.To conclude,allicin plays the potential therapeutic effects on rheumatoid arthritis through the regulation of target genes such as epidermal growth factor receptor and kynureninase.
8.Establishment of a real-time fluorescence-based PCR method for identification of mycobacteria in skin biopsies
Xiao LIU ; Ruoning XUE ; Ruoyu LI ; Yinggai SONG
Chinese Journal of Dermatology 2024;57(11):1016-1021
Objective:To establish a real-time fluorescence-based PCR method for the rapid identification of mycobacteria in skin biopsies.Methods:Primers and probes targeting the genus Mycobacterium and 14 common Mycobacterium species were self-designed, and a real-time fluorescence-based PCR detection system/method was established. Twelve standard strains of Mycobacterium were used for in vitro validation. Tissue samples were collected from 119 patients clinically diagnosed with cutaneous mycobacterial infections at the Department of Dermatology and Venereology, Peking University First Hospital from 2019 to 2021, and were tested with the established real-time fluorescence-based PCR method. Results:In vitro testing demonstrated that the method had good sensitivity and specificity for all the 12 standard strains of Mycobacterium. Among the 119 skin biopsy samples from patients clinically diagnosed with cutaneous mycobacterial infections, the culture positivity rate was only 21.0% (25/119) ; the real-time fluorescence-based PCR yielded a positivity rate of 76.5% (91/119) for the detection of mycobacteria, and 44.5% (53/119) were identified to the species level with Mycobacterium marinum as the predominant species; 31.9% (38/119) were identified only to the genus level. Conclusion:A real-time fluorescence-based PCR method has been established for the efficient detection of mycobacteria in skin tissue samples; however, there remains a possibility of missed diagnoses, other molecular diagnostic techniques are required to be combined to improve the sensitivity and specificity.
9.Research progress on the consistency of self-report and parent-report in children with cancer and its influencing factors
Wenwen ZHAO ; Liming LYU ; Fei WANG ; Longdan XIANG ; Jingyue ZHANG ; Ruoning LI
Chinese Journal of Modern Nursing 2023;29(8):1112-1116
Clinical evaluation of the health outcomes of children with cancer mainly includes two ways: children's self-reporting and parents' agent reporting. Research has confirmed that there are differences between the two reported outcomes, which will have an impact on monitoring the progress of children's disease and guiding clinical decision-making. This article reviews the research progress of the consistency between self-report and parent-report in children with cancer, including common tools, research status and influencing factors, so as to provide a reference for clinical medical and nursing staff to accurately obtain the information of children's condition, promote clinical decision-making, and improve the management of children's symptoms and the quality of care.
10. Platelet-endothelial aggregation receptor 1 and its mediated signalling pathway Advances in the study of the role of platelets and endothelial cells
Ruoning LI ; Zhanli GUO ; Yuan WANG ; Jianjun SUN
Chinese Journal of Clinical Pharmacology and Therapeutics 2023;28(4):438-444
Platelet-aggregation receptor 1 (PEAR1) is a transmembrane receptor identified in 2005 and expressed mainly on platelets and endothelial cells. PEAR1 is a receptor protein that contacts platelets with each other and plays an important role in platelet activation and aggregation. Endothelial cells play an important role in maintaining vascular tone and vascular repair, and PEAR1 regulates the process of tumourigenesis and development by affecting their proliferation and associated neovascularisation. In recent years, PEAR1 has gradually been recognized as a potential target for antithrombotic drugs. This review focuses on elucidating the mechanisms of platelet endothelial aggregation receptor 1 and related signaling pathways in platelets and endothelial cells, and provides new ideas for the study of drug therapy for tumour-associated thrombosis.

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