1.Research progress on the involvement of exosome-mediated intercellular communication in the remodeling and the regulation of invasion and metastasis in the hepatocellular tumor microenvironment
Keqing ZHONG ; Wanhua REN ; Tao LI
Chinese Journal of Hepatology 2025;33(3):280-286
Hepatocellular carcinoma (referred to as liver cancer) tumor microenvironment (TMEs) is a dynamic network system composed of stromal cells, such as liver cancer cells, immune cells, vascular endothelial cells, adipocytes, fibroblasts, and various cytokines that play an important role in the invasion and metastasis of liver cancer. In recent years, there has been an increasing attention on the role of exosomes in the remodeling and the regulation of invasion and metastasis in liver cancer TMEs. Exosomes, as a natural carrier, mediate intercellular communication between liver cancer cells and with other stromal cells, playing an important role in the formation of immunosuppressive TMEs, angiogenesis and hypoxia tolerance, and the coordination of heterogeneity among liver cancer cells. This review summarizes the composition of liver cancer TMEs, the biological functions of exosomes, and the role and mechanism of exosome-mediated liver cancer TMEs between liver cancer cells and other stromal cells, with a focus on exosome involvement in the remodeling and regulating invasion and metastasis in liver cancer TMEs. Simultaneously, it also introduces and explores the application of exosomes in the diagnosis and treatment of liver cancer, with the hope that in-depth research and elucidation of the mechanisms of exosome involvement in the remodeling and regulation of invasion and metastasis in liver cancer TMEs will provide feasible research ideas for novel biological markers and drug delivery carriers.
2.Status quo and issues of ideological education for postgraduate students of general practice based on professional beliefs
Danhua HUANG ; Xin YANG ; Haofeng XU ; Wanhua DONG ; Bingjie HU
Chinese Journal of General Practitioners 2025;24(3):319-325
To analyze the current state and issues of ideological education for graduate students of general practice, from April 10 to Dec 19, 2024, a literature review was conducted on publications from Jan 1, 2001, to Dec 19, 2024, in the CNKI, Wanfang, and VIP databases to identify research entry points. Purposive sampling was used to select postgraduate students majoring in general practice at Guangzhou Medical University and their corresponding faculty as the study participants. A semi-structured in-depth interview method was employed to investigate the current state of ideological and political education. Faculty evaluations of students and their recommendations for ideological and political education were also considered. Thematic framework analysis was applied to the interview data for categorization, integration, and theme extraction. The literature review revealed that enhancing professional identity can strengthen career commitment, leading to the design of an ideological and political education interview outline focused on professional belief and professional identity. The study included 13 general practice postgraduates (mean age: 24.5±1.4 years), of whom 8 were directional students and 5 were non-directional students. Additionally, 7 general practice faculty members were included (mean age: 41.3±5.4 years), with an average of 16.3±5.6 years of experience in general practice education. Five themes were extracted from the interviews: the necessity of ideological and political education, the relationship between professional belief and its educational effects, the intrinsic motivation of ideological beliefs, the influence of external factors on beliefs, and effective approaches to ideological and political education. The study also identified current issues in ideological and political education for general practice postgraduates, including inadequate career planning guidance, reluctance to work in underdeveloped areas, over-reliance on the role modeling of faculty mentors, lack of systematic courses and frameworks for ideological and political education, and limited opportunities for team projects and communication platforms. The current state of ideological and political education for general practice postgraduates reveals deficiencies in career planning support, systematic course construction, practical opportunities, and communication platforms. Education methods remain overly simplistic and are significantly influenced by external factors, underscoring the need for optimization and enhancement.
3.Meta-integration of transitional qualitative experiences in adolescents with inflammatory bowel disease
Hui LIU ; Mingfen LIU ; Lisha GUO ; Meiqing PENG ; Wanhua XIE
Modern Clinical Nursing 2025;24(7):76-83
Objective To systematically evaluate the psychological characteristics of adolescent inflammatory bowel disease(IBD)patients during the transition period and provide evidence-based guidance for healthcare professionals in developing transition management strategies.Methods A systematic search was conducted across The Cochrane Library,PubMed,Web of Science,CINAHL,Embase,SinoMed,CNKI,Wanfang,and VIP databases for qualitative studies on adolescent IBD patients during transition,from database inception to May 2024.Eligible studies were critically appraised,and themes were synthesized using the meta-aggregation approach of meta-synthesis.Results Twelve studies were included,yielding 13 findings that were synthesized into five categories:self-development challenges,healthcare system transition barriers,family support conflicts,social adaptation difficulties,and lack of societal support systems.Conclusion Adolescents with IBD experience complex psychological challenges during transition,characterized by excessive psychological burdens,inadequate healthcare support,and insufficient societal recognition.Targeted interventions are needed to improve psychological outcomes during this critical phase.
4.Correlation between serum metabolomic characteristics and risk of myocardial infarction in patients with coronary atherosclerosis
Jin LIU ; Wanhua CHEN ; Yueru REN
Journal of Xi'an Jiaotong University(Medical Sciences) 2025;46(3):402-409
Objective To explore the correlation between serum metabolomics characteristics and the risk of myocardial infarction in patients with coronary atherosclerosis(CAS)so as to provide new ideas and targets for clinical prevention and treatment of myocardial infarction.Methods A total of 180 CAS patients treated in our hospital from June 2018 to June 2022 were selected as the study subjects and divided into control group(non-myocardial infarction,n=138)and observation group(myocardial infarction,n=42)according to follow-up.Propensity score matching method was used to perform 1∶1 matching,and a total of 34 pairs were successfully matched.The serum samples of patients were detected by mass spectrometry chip in metabolomics technology.Principal component analysis(PCA),partial least square discriminant analysis(PLS-DA),and orthogonal partial least square discriminant analysis(OPLS-DA)results were compared among groups to screen out different metabolites.The diagnostic value of differential metabolites was evaluated by receiver operating characteristic(ROC)curve.The samples were cluster analyzed by agglomerative hierarchical clustering,and the pathway enrichment analysis of differential metabolites was carried out.Results There were significant differences in the mass spectra of serum samples from the two groups of CAS patients.PC A results showed that there was a certain separation trend between the overall level of serum metabolism in the two groups,but the trend was not significant(R2X=0.654,Q2Y=0.719).PLS-DA analysis showed the separation trend of the two groups of samples(R2X=0.582,R2Y=0.810,Q2Y=0.675).Further OPLS-DA analysis showed that the two groups of samples had an obvious separation trend(R2X=0.595,R2Y=0.831,Q2Y=0.742).Twelve differential metabolites between groups were screened by VIP value>1 and Wilcoon-Mann-Whitney test;of them three were upregulated and nine were downregulated.Upregulated D-glucose and downregulated glycocholic acid,ursodeoxycholic acid,nicotinic acid acid,niacinamide and succinic acid were of high value as diagnostic markers for myocardial infarction.Differential metabolite pathway analysis showed that among the eight metabolic pathways that may be disturbed by differential metabolites,non-alcoholic fatty liver,niacin and niacinamide metabolism,and pathways associated with type 2 diabetes mellitus Impact ≥ 0.1 might be potential pathways in the pathogenesis of myocardial infarction in CAS patients.Conclusion Serum levels of glycinocholic acid,D-glucose,ursodeoxycholic acid,niacin,niacinamide,and succinic acid can be used as potential markers to distinguish the risk of myocardial infarction in patients with CAS.The metabolic pathways affected mainly include non-alcoholic fatty liver disease,niacin and niacinamide metabolism,and type 2 diabetes mellitus-related pathways.
5.Correlation between serum metabolomic characteristics and risk of myocardial infarction in patients with coronary atherosclerosis
Jin LIU ; Wanhua CHEN ; Yueru REN
Journal of Xi'an Jiaotong University(Medical Sciences) 2025;46(3):402-409
Objective To explore the correlation between serum metabolomics characteristics and the risk of myocardial infarction in patients with coronary atherosclerosis(CAS)so as to provide new ideas and targets for clinical prevention and treatment of myocardial infarction.Methods A total of 180 CAS patients treated in our hospital from June 2018 to June 2022 were selected as the study subjects and divided into control group(non-myocardial infarction,n=138)and observation group(myocardial infarction,n=42)according to follow-up.Propensity score matching method was used to perform 1∶1 matching,and a total of 34 pairs were successfully matched.The serum samples of patients were detected by mass spectrometry chip in metabolomics technology.Principal component analysis(PCA),partial least square discriminant analysis(PLS-DA),and orthogonal partial least square discriminant analysis(OPLS-DA)results were compared among groups to screen out different metabolites.The diagnostic value of differential metabolites was evaluated by receiver operating characteristic(ROC)curve.The samples were cluster analyzed by agglomerative hierarchical clustering,and the pathway enrichment analysis of differential metabolites was carried out.Results There were significant differences in the mass spectra of serum samples from the two groups of CAS patients.PC A results showed that there was a certain separation trend between the overall level of serum metabolism in the two groups,but the trend was not significant(R2X=0.654,Q2Y=0.719).PLS-DA analysis showed the separation trend of the two groups of samples(R2X=0.582,R2Y=0.810,Q2Y=0.675).Further OPLS-DA analysis showed that the two groups of samples had an obvious separation trend(R2X=0.595,R2Y=0.831,Q2Y=0.742).Twelve differential metabolites between groups were screened by VIP value>1 and Wilcoon-Mann-Whitney test;of them three were upregulated and nine were downregulated.Upregulated D-glucose and downregulated glycocholic acid,ursodeoxycholic acid,nicotinic acid acid,niacinamide and succinic acid were of high value as diagnostic markers for myocardial infarction.Differential metabolite pathway analysis showed that among the eight metabolic pathways that may be disturbed by differential metabolites,non-alcoholic fatty liver,niacin and niacinamide metabolism,and pathways associated with type 2 diabetes mellitus Impact ≥ 0.1 might be potential pathways in the pathogenesis of myocardial infarction in CAS patients.Conclusion Serum levels of glycinocholic acid,D-glucose,ursodeoxycholic acid,niacin,niacinamide,and succinic acid can be used as potential markers to distinguish the risk of myocardial infarction in patients with CAS.The metabolic pathways affected mainly include non-alcoholic fatty liver disease,niacin and niacinamide metabolism,and type 2 diabetes mellitus-related pathways.
6.Meta-integration of transitional qualitative experiences in adolescents with inflammatory bowel disease
Hui LIU ; Mingfen LIU ; Lisha GUO ; Meiqing PENG ; Wanhua XIE
Modern Clinical Nursing 2025;24(7):76-83
Objective To systematically evaluate the psychological characteristics of adolescent inflammatory bowel disease(IBD)patients during the transition period and provide evidence-based guidance for healthcare professionals in developing transition management strategies.Methods A systematic search was conducted across The Cochrane Library,PubMed,Web of Science,CINAHL,Embase,SinoMed,CNKI,Wanfang,and VIP databases for qualitative studies on adolescent IBD patients during transition,from database inception to May 2024.Eligible studies were critically appraised,and themes were synthesized using the meta-aggregation approach of meta-synthesis.Results Twelve studies were included,yielding 13 findings that were synthesized into five categories:self-development challenges,healthcare system transition barriers,family support conflicts,social adaptation difficulties,and lack of societal support systems.Conclusion Adolescents with IBD experience complex psychological challenges during transition,characterized by excessive psychological burdens,inadequate healthcare support,and insufficient societal recognition.Targeted interventions are needed to improve psychological outcomes during this critical phase.
7.Status quo and issues of ideological education for postgraduate students of general practice based on professional beliefs
Danhua HUANG ; Xin YANG ; Haofeng XU ; Wanhua DONG ; Bingjie HU
Chinese Journal of General Practitioners 2025;24(3):319-325
To analyze the current state and issues of ideological education for graduate students of general practice, from April 10 to Dec 19, 2024, a literature review was conducted on publications from Jan 1, 2001, to Dec 19, 2024, in the CNKI, Wanfang, and VIP databases to identify research entry points. Purposive sampling was used to select postgraduate students majoring in general practice at Guangzhou Medical University and their corresponding faculty as the study participants. A semi-structured in-depth interview method was employed to investigate the current state of ideological and political education. Faculty evaluations of students and their recommendations for ideological and political education were also considered. Thematic framework analysis was applied to the interview data for categorization, integration, and theme extraction. The literature review revealed that enhancing professional identity can strengthen career commitment, leading to the design of an ideological and political education interview outline focused on professional belief and professional identity. The study included 13 general practice postgraduates (mean age: 24.5±1.4 years), of whom 8 were directional students and 5 were non-directional students. Additionally, 7 general practice faculty members were included (mean age: 41.3±5.4 years), with an average of 16.3±5.6 years of experience in general practice education. Five themes were extracted from the interviews: the necessity of ideological and political education, the relationship between professional belief and its educational effects, the intrinsic motivation of ideological beliefs, the influence of external factors on beliefs, and effective approaches to ideological and political education. The study also identified current issues in ideological and political education for general practice postgraduates, including inadequate career planning guidance, reluctance to work in underdeveloped areas, over-reliance on the role modeling of faculty mentors, lack of systematic courses and frameworks for ideological and political education, and limited opportunities for team projects and communication platforms. The current state of ideological and political education for general practice postgraduates reveals deficiencies in career planning support, systematic course construction, practical opportunities, and communication platforms. Education methods remain overly simplistic and are significantly influenced by external factors, underscoring the need for optimization and enhancement.
8.Research progress on the involvement of exosome-mediated intercellular communication in the remodeling and the regulation of invasion and metastasis in the hepatocellular tumor microenvironment
Keqing ZHONG ; Wanhua REN ; Tao LI
Chinese Journal of Hepatology 2025;33(3):280-286
Hepatocellular carcinoma (referred to as liver cancer) tumor microenvironment (TMEs) is a dynamic network system composed of stromal cells, such as liver cancer cells, immune cells, vascular endothelial cells, adipocytes, fibroblasts, and various cytokines that play an important role in the invasion and metastasis of liver cancer. In recent years, there has been an increasing attention on the role of exosomes in the remodeling and the regulation of invasion and metastasis in liver cancer TMEs. Exosomes, as a natural carrier, mediate intercellular communication between liver cancer cells and with other stromal cells, playing an important role in the formation of immunosuppressive TMEs, angiogenesis and hypoxia tolerance, and the coordination of heterogeneity among liver cancer cells. This review summarizes the composition of liver cancer TMEs, the biological functions of exosomes, and the role and mechanism of exosome-mediated liver cancer TMEs between liver cancer cells and other stromal cells, with a focus on exosome involvement in the remodeling and regulating invasion and metastasis in liver cancer TMEs. Simultaneously, it also introduces and explores the application of exosomes in the diagnosis and treatment of liver cancer, with the hope that in-depth research and elucidation of the mechanisms of exosome involvement in the remodeling and regulation of invasion and metastasis in liver cancer TMEs will provide feasible research ideas for novel biological markers and drug delivery carriers.
9.Effect of ADU-S100/doxorubicin in situ vaccine on diffuse large B-cell lymphoma and its mechanism
Pengli XIAO ; Shuli GUO ; Huirui WANG ; Huiyun MAO ; Wanhua AN
Journal of Leukemia & Lymphoma 2024;33(1):29-36
Objective:To explore the antitumor effect of ADU-S100/doxorubicin in situ vaccine on diffuse large B-cell lymphoma (DLBCL) and its mechanism.Methods:The 6-week-old female BALB/c mice were selected, and the bilateral murine subcutaneous B-cell lymphoma model was established with murine B-cell lymphoma A20 cells. The subcutaneous tumor-bearing mice were randomly divided into untreated group (without treatment), ADU-S100 in situ vaccine treatment group (intratumoral injection of interferon gene stimulating factor agonist ADU-S100), doxorubicin in situ vaccine treatment group (intratumoral injection of doxorubicin), and ADU-S100/doxorubicin in situ vaccine treatment group (intratumoral injection of ADU-S100 and doxorubicin) by using random number table method, with 5 mice in each group. The right tumors of the bilateral subcutaneous tumor-bearing mice were defined as proximal tumors, and the left tumors of the bilateral subcutaneous tumor-bearing mice were defined as distal tumors. Only the proximal tumors were treated via the intratumoral route, and the distal tumors were not treated. On day 23 after tumor inoculation, the percentages of CD11c + dendritic cells (DC), CD8 + CD11c + DC and CD80 + CD11c + DC in the spleen of mice in each group were detected by flow cytometry. The splenocytes of mice in each group were stimulated with A20 tumor cell lysate in vitro, the percentages of 5'-ethynyl-2'-deoxyuridine-positive (EdU +) cells and tumor necrosis factor-α-positive (TNF-α +) cells in CD8 + T cells in each in situ vaccine treatment group were detected by flow cytometry, and the killing effect of cytotoxic T lymphocyte (CTL) in each group was measured by using the lactate dehydrogenase (LDH) cytotoxicity assay kit. The mice treated with ADU-S100/doxorubicin in situ vaccine were intraperitoneally injected with anti-mouse CD8α (clone 53-6.7) mAb or isotype control on days 7, 12 and 17 after tumor inoculation to eliminate CD8 + cells. On day 23 after tumor inoculation, the proximal and distal tumor volumes of mice in the ADU-S100/doxorubicin in situ vaccine combined with anti-mouse CD8α (clone 53-6.7) mAb or isotype control treatment group were measured, the percentages of CD8 + T cells and CD8 + CD11c + DC in the spleen of tumor-bearing mice in these two groups were detected by flow cytometry, and the infiltration of CD8 + T cells in the tumor tissues from these two groups was detected by immunohistochemistry (IHC) staining. Results:On days 11, 14, 17, 20 and 23 after tumor inoculation, the proximal and distal tumor volumes of mice in each treated group were lower than those in the untreated group (all P < 0.05). The proportions of CD11c + DC in the spleen of the untreated group, ADU-S100 in situ vaccine treatment group, doxorubicin in situ vaccine treatment group and ADU-S100/doxorubicin in situ vaccine treatment group were (4.92±0.63)%, (7.54±0.84)%, (7.45±0.86)% and (11.63±0.85)%, respectively, and the difference was statistically significant ( F = 72.30, P < 0.001); the proportions of CD8 + CD11c + DC were (1.36±0.34)%, (4.02±0.43)%, (4.22±0.61)% and (6.11±0.73)%, respectively, and the difference was statistically significant ( F = 76.09, P < 0.001); the proportions of CD80 + CD11c + DC were (0.51±0.24)%, (1.69±0.23)%, (1.82±0.25)% and (4.09±0.39)%, respectively, and the difference was statistically significant ( F = 167.40, P < 0.001). The CTL responses and the proportion of EdU + cells and TNF-α + cells in CD8 + T cells in each in situ vaccine treatment group were higher than those in the untreated group (all P < 0.05). Furthermore, the enhanced CTL responses and the increased proportion of EdU + cells and TNF-α + cells in CD8 + T cells were observed in the ADU-S100/doxorubicin in situ vaccine treatment group as compared to the ADU-S100 in situ vaccine treatment group and doxorubicin in situ vaccine treatment group (all P < 0.05). The proportions of CD8 + T cells and CD8 + CD11c + DC in the spleen of mice treated with ADU-S100/doxorubicin in situ vaccine and anti-mouse CD8α mAb were lower than those in ADU-S100/doxorubicin in situ vaccine and isotype control group (both P < 0.05) and both proximal and distal tumor volumes of mice treated with ADU-S100/doxorubicin in situ vaccine and anti-mouse CD8α mAb were larger than those in ADU-S100/doxorubicin in situ vaccine and isotype control group (both P < 0.05). Conclusions:ADU-S100/doxorubicin in situ vaccine can induce profound regression of proximal tumors in bilateral murine subcutaneous B-cell lymphoma model and generate systemic immune responses capable of partially inhibiting distant tumor growth, and the antitumor efficacy of ADU-S100/doxorubicin in situ vaccine may require CD8 + CD11c + DC-mediated CD8 + T cell immune responses.
10.Expression and clinical significance of zinc finger protein 382 in diffuse large B-cell lymphoma
Sizhe LIU ; Wanhua AN ; Shuli GUO ; Huirui WANG ; Pengli XIAO ; Wanli WANG ; Shuanglin WANG
Journal of Xinxiang Medical College 2024;41(1):37-42
Objective To investigate the expression of zinc finger protein 382(ZNF382)in diffuse large B-cell lymphoma(DLBCL)tissue and its relationship with clinical pathological characteristics and prognosis of DLBCL patients.Methods A total of 57 DLBCL patients admitted to the Department of Hematology,Luoyang Central Hospital from January 2014 to December 2018 were selected as the research subjects.The biopsy pathological specimens and clinical data of DLBCL patients were collected;another 20 patients of reactive proliferative lymph node tissue preserved in the Department of Pathology,Luoyang Central Hospital were taken as the control group.The expression of ZNF382 in DLBCL tissue and reactive proliferative lymph node tissue was detected by En vision two-step method.The difference of ZNF382 expression was compared between DLBCL tissue and reactive proliferative lymph node tissue.The correlations of ZNF382 expression with the clinical features such as age,gender,primary tumor site,Ann Arbor stage,international prognostic index(IPI)score,Hans typing,B-symptoms,bone marrow infiltration,giant masses,Eastern Cooperative Oncology Group(ECOG)score,β2-microglobulin(β2-MG),serum lactate dehydrogenase(LDH),Ki67,and chemotherapy regimen of DLBCL patients were analyzed by univariate analysis;the survival curve was drawed by Kaplan Meier method,and the univariate and multivariate survival analysis were performed by log-rank tests and Cox proportional risk regression models.Results The expression level of ZNF382 in DLBCL tissue was significantly lower than that in reactive proliferative lymph node tissue(Z=-5.056,P<0.01).The expression level of ZNF382 was correlated with IPI score,Ann Arbor stage,Hans typing,B-symptoms,bone marrow infiltration and giant masses of DLBCL patients(P<0.05);the expression level of ZNF382 was not associated to gender,age,primary site,ECOG score,β2-MG,serum LDH,Ki67,and whether the chemotherapy regimen combined with rituximab or not of DLBCL patients(P>0.05).Among the 57 DLBCL patients,the treatment was effective in 36 patients(63.20%)and ineffective in 21 patients(36.80%);the expression level of ZNF382 in tumor tissue of DLBCL patients with effective treatment was significantly higher than that of DLBCL patients with ineffective treatment(Z=-2.895,P<0.05).The 2-year event free survival rate of DLBCL patients in the ZNF382 high expression group was significantly higher than that in the ZNF382 low expression group(x2=17.955,P<0.001).The results of univariate survival analysis showed that female,primary lymph nodes,B-symptoms,bone marrow infiltration,giant masses,IPI score≥3,elevated β2-MG,Ki67>70%,non-germinal center B-cell-like lymphoma,Ann Arbor stageⅢ-Ⅳ and low expression of ZNF382 were risk factors for poor prognosis in DLBCL patients(P<0.05).The results of multivariate analysis showed that primary lymph nodes,Ann Arbor stage Ⅲ-Ⅳ and low expression of ZNF382 were independent influencing factors for poor prognosis in DLBCL patients(P<0.05).Conclusion ZNF382 protein is low expressed in the tumor tissues of DLBCL patients,which is closely related to the occurrence,development and prognosis of DLBCL;and it can be used as an indicator for evaluating the prognosis of DLBCL.

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