1.Comparative study of cardiac morphology, size and function between fetuses with tetralogy of Fallot and fetuses with malalignment ventricular septal defect and pulmonary stenosis by multi-parameter quantitative echocardiography
Shuli YANG ; Bowen ZHAO ; Mei PAN ; Xiaohui PENG ; Ran CHEN ; Yuanshi TIAN ; Min DI ; Heqing GUO
Chinese Journal of Ultrasonography 2025;34(2):139-148
Objective:To analyze the differences in heart size,shape and function between fetuses with tetralogy of Fallot(TOF)and fetuses with malalignment ventricular septal defect(VSD)and pulmonary stenosis(PS)(named as,mild TOF)by fetal heart quantification(fetal HQ)and multi-parameter fetal echocardiography.Methods:From June 2021 to June 2023,50 fetuses with TOF(TOF group)diagnosed by fetal echocardiography at the Department of Diagnostic Ultrasound & Echocardiography Sir Run Run Shaw Hospital,Zhejiang University College of Medicine and 34 fetuses with VSD and PS matched to gestational age(mild TOF group)were retrospectively selected. Cardiovascular parameters were measured by 2D echocardiography,M-mode echocardiography and fetal HQ,including aortic dimension(AO)and its Z-score(AO Z-score),pulmonary artery diameter(PA)and its Z-score(PA Z-score),PA/AO ratio,main pulmonary artery diameter(MPA)and its Z-score(MPA Z-score),left pulmonary artery diameter(LPA)and its Z-score(LPA Z-score),right pulmonary artery diameter(RPA)and its Z-score(RPA Z-score),McGoon index(MGI),tricuspid annular diameter(TV)and its Z-score(TV Z-score),mitral annular diameter(MV)and its Z-score(MV Z-score),and MV/TV ratio. Measurements of global ventricular morphologic parameters included cardiac axis,left and right ventricular transverse diameters(LVW,RVW)and their ratio(LVW/RVW),left and right ventricular long diameters(LVL,RVL)and LVL/RVL ratio,left and right ventricular areas(LVA,RVA)and LVA/RVA ratio,global spherical index(GSI)and its Z-score,four chamber view transverse diameter(4CV-Width-ED),four chamber view end-diastolic longitudinal diameter(4CV-Length-ED),four chamber view end-diastolic area(4CV-Area-ED). Measurements of left and right global ventricular functional parameters included fractional left ventricular and right ventricular area changes(LVFAC,RVFAC),left ventricular ejection fraction(LVEF),left ventricular and right ventricular global longitudinal strains(LVGLS,RVGLS);end diastolic width diameter(Width-ED),SI and fractional shortening rate(FS)of 24 segments of left and right ventricles. The differences of the above parameters between the two groups were analyzed and compared,and the relationships between absolute values of GLS in left and right ventricles of TOF fetus and PA Z-score,MPA Z-score and PA/AO were analyzed. Binary Logistic regression model was used to select the best variables,and ROC curve was adopted to analyze the predictive values of ultrasonic parameter variables on TOF.Results:There were statistically significant differences in MV,TV,RVW,RVL,LVL,LVA,RVA,4CV-Length-ED,LVGLS,RVGLS,RVFAC,PA/AO,MPA,RPA,LPA,MGI,PA and PA Z-score between TOF group and mild TOF group(all P<0.05). The Width-ED values of all segments of left ventricle were statistically different between TOF group and mild TOF group(all P<0.05). There were statistical differences in SI between LV segments 4~6 and 8~24,and RV segments 1~21(all P<0.05). The FS values between the 8th and 10th to 18th segments of RV revealed statistical differences(all P<0.05). There were no statistical differences in the other parameters(all P>0.05). The absolute value of LVGLS in TOF fetuses was positively correlated with PA Z-score,MPA Z-score and PA/AO( r = 0.313,0.344,0.304,all P<0.05),and the absolute value of RVGLS was positively correlated with PA Z-score,MPA Z-score,and PA/AO( r = 0.323,0.334,0.357,all P<0.05). Binary Logistic regression model analysis confirmed that LVGLS,RVFAC and PA/AO were predictive variables. ROC curve analysis showed that the areas under the curves of LVGLS,RVFAC and PA/AO for predicting TOF were 0.746,0.693 and 0.849 respectively. The combined prediction efficiency was higher,and the area under the curve was 0.906. Conclusions:Fetal HQ combined with multiple fetal echocardiographic quantification indices can evaluate the differences in fetal heart size,shape and function between TOF and mild TOF. It is expected to provide important reference information in prenatal diagnosis and consultation for fetuses with TOF and mild TOF.
2.Mast cell-derived chemokine C-C motif ligand 5 affects the migration of CD8 + T cells from vitiligo patients under oxidative stress
Pu SONG ; Yu LIU ; Sen GUO ; Shuli LI ; Ling LIU ; Chunying LI
Chinese Journal of Dermatology 2025;58(9):839-843
Objective:To investigate the effect of mast cell-derived chemokine C-C motif ligand 5 (CCL5) on the migration of CD8 + T cells from vitiligo patients under oxidative stress conditions. Methods:From January 2017 to January 2023, 10 patients with progressive segmental vitiligo, 10 patients with non-segmental vitiligo, and 10 healthy individuals were collected from the Department of Dermatology, Xijing Hospital. Skin tissue samples were obtained from the lesions of vitiligo patients and from the normal skin of healthy individuals, with sampling sites including the face, neck, and upper extremities, and toluidine blue staining was performed to analyze the characteristics of mast cells infiltrating the skin lesions. The effect of H 2O 2 treatment on mast cells was investigated in Transwell chambers. Peripheral blood mononuclear cells (PBMCs) from vitiligo patients were added to the upper chamber, while the human mast cell line LAD2 was added to the lower chamber and divided into 4 groups to receive different treatments: untreated group receiving no special treatment, H 2O 2 group pretreated with H 2O 2, H 2O 2 + neutralization antibody group pretreated with H 2O 2 followed by the treatment with CCL5/RANTES-neutralizing antibodies, and H 2O 2 + PF group pretreated with H 2O 2 followed by the treatment with a Janus kinase 3/non-receptor protein tyrosine kinase selective inhibitor PF-06651600. After 6 hours of co-incubation, cell suspensions were collected from the lower chamber. The number of CD8 + T cells was counted using flow cytometry, and the CCL5 level in the cell culture supernatant was detected using enzyme-linked immunosorbent assay. One-way analysis of variance was used to analyze differences among groups, and least significant difference- t test was used for multiple comparisons. Pearson correlation analysis was performed for correlation analysis. Results:In the 200 × magnification field, the numbers of infiltrating mast cells significantly differed among segmental vitiligo lesions, non-segmental vitiligo lesions, and normal skin tissues (15.7 ± 3.3, 20.9 ± 3.9, 7.2 ± 2.9, respectively; F = 8.07, P = 0.002) ; additionally, the number of infiltrating mast cells was significantly higher in the segmental or non-segmental vitiligo lesions than in the normal skin tissues (LSD- t = 3.50, 5.70, P = 0.047, 0.001, respectively), but there was no significant difference between the segmental and non-segmental vitiligo lesions (LSD- t = 2.20, P = 0.293). A significant positive correlation was observed between the number of infiltrating mast cells and that of CD8 + T cells in the vitiligo lesions ( r = 0.82, P = 0.004). The numbers of CD8 + T cells and CCL5 levels significantly differed among the untreated group, H 2O 2 group, H 2O 2 + neutralization antibody group, and H 2O 2 + PF group (CD8 + T cells: 197.0 ± 45.9, 580.4 ± 62.6, 296.0 ± 43.2, 398.6 ± 62.8, respectively; CCL5: 2.2 ± 0.6 pg/ml, 9.9 ± 1.3 pg/ml, 3.4 ± 0.4 pg/ml, 6.33 ± 0.7 pg/ml, respectively; F = 11.03, 17.77, respectively, both P < 0.001) ; additionally, the H 2O 2 group showed significantly increased numbers of CD8 + T cells and CCL5 levels compared with the untreated group, H 2O 2 + neutralization antibody group, and H 2O 2 + PF group (all P < 0.05) . Conclusion:Mast cells may be involved in the pathogenesis of vitiligo under oxidative stress, and mast cell-derived CCL5 appears to contribute to the occurrence and development of vitiligo by affecting CD8 + T cell migration.
3.Mast cell-derived chemokine C-C motif ligand 5 affects the migration of CD8 + T cells from vitiligo patients under oxidative stress
Pu SONG ; Yu LIU ; Sen GUO ; Shuli LI ; Ling LIU ; Chunying LI
Chinese Journal of Dermatology 2025;58(9):839-843
Objective:To investigate the effect of mast cell-derived chemokine C-C motif ligand 5 (CCL5) on the migration of CD8 + T cells from vitiligo patients under oxidative stress conditions. Methods:From January 2017 to January 2023, 10 patients with progressive segmental vitiligo, 10 patients with non-segmental vitiligo, and 10 healthy individuals were collected from the Department of Dermatology, Xijing Hospital. Skin tissue samples were obtained from the lesions of vitiligo patients and from the normal skin of healthy individuals, with sampling sites including the face, neck, and upper extremities, and toluidine blue staining was performed to analyze the characteristics of mast cells infiltrating the skin lesions. The effect of H 2O 2 treatment on mast cells was investigated in Transwell chambers. Peripheral blood mononuclear cells (PBMCs) from vitiligo patients were added to the upper chamber, while the human mast cell line LAD2 was added to the lower chamber and divided into 4 groups to receive different treatments: untreated group receiving no special treatment, H 2O 2 group pretreated with H 2O 2, H 2O 2 + neutralization antibody group pretreated with H 2O 2 followed by the treatment with CCL5/RANTES-neutralizing antibodies, and H 2O 2 + PF group pretreated with H 2O 2 followed by the treatment with a Janus kinase 3/non-receptor protein tyrosine kinase selective inhibitor PF-06651600. After 6 hours of co-incubation, cell suspensions were collected from the lower chamber. The number of CD8 + T cells was counted using flow cytometry, and the CCL5 level in the cell culture supernatant was detected using enzyme-linked immunosorbent assay. One-way analysis of variance was used to analyze differences among groups, and least significant difference- t test was used for multiple comparisons. Pearson correlation analysis was performed for correlation analysis. Results:In the 200 × magnification field, the numbers of infiltrating mast cells significantly differed among segmental vitiligo lesions, non-segmental vitiligo lesions, and normal skin tissues (15.7 ± 3.3, 20.9 ± 3.9, 7.2 ± 2.9, respectively; F = 8.07, P = 0.002) ; additionally, the number of infiltrating mast cells was significantly higher in the segmental or non-segmental vitiligo lesions than in the normal skin tissues (LSD- t = 3.50, 5.70, P = 0.047, 0.001, respectively), but there was no significant difference between the segmental and non-segmental vitiligo lesions (LSD- t = 2.20, P = 0.293). A significant positive correlation was observed between the number of infiltrating mast cells and that of CD8 + T cells in the vitiligo lesions ( r = 0.82, P = 0.004). The numbers of CD8 + T cells and CCL5 levels significantly differed among the untreated group, H 2O 2 group, H 2O 2 + neutralization antibody group, and H 2O 2 + PF group (CD8 + T cells: 197.0 ± 45.9, 580.4 ± 62.6, 296.0 ± 43.2, 398.6 ± 62.8, respectively; CCL5: 2.2 ± 0.6 pg/ml, 9.9 ± 1.3 pg/ml, 3.4 ± 0.4 pg/ml, 6.33 ± 0.7 pg/ml, respectively; F = 11.03, 17.77, respectively, both P < 0.001) ; additionally, the H 2O 2 group showed significantly increased numbers of CD8 + T cells and CCL5 levels compared with the untreated group, H 2O 2 + neutralization antibody group, and H 2O 2 + PF group (all P < 0.05) . Conclusion:Mast cells may be involved in the pathogenesis of vitiligo under oxidative stress, and mast cell-derived CCL5 appears to contribute to the occurrence and development of vitiligo by affecting CD8 + T cell migration.
4.Expression levels and clinical significance of microRNA-152-3p and sex determining region-box transcription factor 5 in gastric cancer tissues
Shuli GUO ; Chen YANG ; Dan LU ; Xiaomin GUO ; Shuhua GUO ; Xinfeng HAN
Journal of Clinical Medicine in Practice 2025;29(17):33-37
Objective To investigate the expression levels of microRNA-152-3p(miR-152-3p)and sex determining region-box transcription factor 5(SOX5)in gastric cancer(GC)tissues and their clinical significance.Methods A total of 120 GC patients were selected as study subjects.Re-al-time quantitative polymerase chain reaction(qRT-PCR)was used to detect the expression levels of miR-152-3p and SOX5,and their relationships with the clinicopathological characteristics of GC pa-tients were analyzed.The Kaplan-Meier method was applied to draw survival curves,and the Cox re-gression model was used to screen the prognostic influencing factors of GC patients.Results The ex-pression level of miR-152-3p in GC tissues was lower than that in adjacent non-cancerous tissues,while the expression level of SOX5 was higher than that in adjacent non-cancerous tissues(P<0.05).The expressions of miR-152-3p and SOX5 in GC tissues were all associated with lymph node metastasis,degree of differentiation,and TNM stage(P<0.05).The expression level of miR-152-3p was negatively correlated with that of SOX5(r=-0.512,P<0.05),and there were targeted binding sites between miR-152-3p and SOX5.The 5-year specific survival rate of the low miR-152-3p expression group was lower than that of the high miR-152-3p expression group(60.53%versus 84.09%,x2=7.256,P<0.05).The 5-year specific survival rate of the high SOX5 expression group was 63.10%,which was lower than 83.33%of the low SOX5 expression group,with a statis-tically significant difference(x2=4.840,P<0.05).Multivariate Cox regression analysis showed that the expression levels of miR-152-3p and SOX5,as well as the TNM stage,were all independent prog-nostic influencing factors for GC patients(P<0.05).Conclusion Low expressions of miR-152-3p and high expression of SOX5 are observed in GC tissues,and their expression levels are closely re-lated to clinicopathological characteristics such as TNM stage and patients' prognosis.
5.Current status and influencing factors of nutrition support specialist nurses' knowledge, attitude and practice about nutrition nursing practice
Ni YANG ; Yuan XU ; Xinyi ZHOU ; Ge LIU ; Yanming DING ; Shuli GUO ; Qian LU ; Haibo DENG ; Ying LIU ; Yufen MA
Chinese Journal of Modern Nursing 2025;31(13):1698-1704
Objective:To investigate the current status of nutritional support specialist nurses' knowledge, attitude and practice about nutrition nursing practice and analyze their influencing factors, so as to provide reference for optimizing and improving the level of nutritional support specialist nurses' knowledge, attitude and practice, and constructing a training program for nutritional support specialist nurses.Methods:From October to November 2023, 557 nutritional support specialist nurses in 28 provinces, autonomous regions, and municipalities directly under the central government of China were selected for the survey using the convenience sampling method. General information questionnaire and Nutrition Nursing Practice Knowledge, Attitude and Practice Questionnaire were used to conduct the survey. Multiple linear regression was used to explore the influencing factors of knowledge, attitude and practice.Results:A total of 557 questionnaires were distributed and 507 questionnaires were effectively recovered, with an effective recovery rate of 91.0%. The nutrition nursing practice knowledge dimension scores, attitude dimension scores, and practice dimension scores of 507 nutritional support specialist nurses were 30.00 (28.00, 31.00) , 47.00 (41.00, 50.00) , (22.65±6.77) , respectively. Multiple linear regression analyses showed that education was an influencing factor in the knowledge dimension of nutrition nursing practice among nutritional support nurse specialists ( P<0.05) ; title, hospital level, and years of experience as a nutritional support nurse specialist were influencing factors in the attitude dimension of nutrition nursing practice ( P<0.05) . Conclusions:Nutritional support specialist nurses have a good knowledge base of nutrition nursing practice and a positive attitude, but their practices need to be further improved. Knowledge, attitude, and practice are affected by multiple factors such as education, title, hospital level, and number of years in the professional field. In the process of nurse specialist training, managers should pay attention to the learning needs of nurses at different levels, carry out targeted training, establish a standard workflow for nurse specialists, and emphasize the construction of talents in primary hospitals, so as to promote the high-quality development of nutrition support specialist nurses.
6.Role and value of nurses in nutritional screening and assessment of hospitalized patients
Yuan XU ; Yanming DING ; Ni YANG ; Ge LIU ; Qian LU ; Ying LIU ; Shuli GUO ; Yufen MA
Chinese Journal of Modern Nursing 2025;31(13):1687-1691
The participation of nurses in nutritional screening and assessment is not only the foundation for achieving full coverage of nutritional screening and assessment for hospitalized patients, but also an important guarantee for preventing and improving adverse clinical outcomes in hospitalized patients. Nurses should start by distinguishing between the concepts of nutritional screening and nutritional assessment, selecting patient-appropriate nutritional screening and assessment tools, and accurately timing nutritional screening and assessment to correctly perform nutritional screening and assessment. At the same time, nurses have a unique role and value in identifying nutritional risks in hospitalized patients, performing nutritional screening and assessment, and multidisciplinary nutritional diagnosis and treatment. Although nurses face many challenges in practice, they can address these challenges through artificial intelligence empowerment, the development of nutritional screening and assessment standard processes, the provision of health education to assist patients in self-management, and the establishment of training systems.
7.Current status and influencing factors of nutrition support specialist nurses' knowledge, attitude and practice about nutrition nursing practice
Ni YANG ; Yuan XU ; Xinyi ZHOU ; Ge LIU ; Yanming DING ; Shuli GUO ; Qian LU ; Haibo DENG ; Ying LIU ; Yufen MA
Chinese Journal of Modern Nursing 2025;31(13):1698-1704
Objective:To investigate the current status of nutritional support specialist nurses' knowledge, attitude and practice about nutrition nursing practice and analyze their influencing factors, so as to provide reference for optimizing and improving the level of nutritional support specialist nurses' knowledge, attitude and practice, and constructing a training program for nutritional support specialist nurses.Methods:From October to November 2023, 557 nutritional support specialist nurses in 28 provinces, autonomous regions, and municipalities directly under the central government of China were selected for the survey using the convenience sampling method. General information questionnaire and Nutrition Nursing Practice Knowledge, Attitude and Practice Questionnaire were used to conduct the survey. Multiple linear regression was used to explore the influencing factors of knowledge, attitude and practice.Results:A total of 557 questionnaires were distributed and 507 questionnaires were effectively recovered, with an effective recovery rate of 91.0%. The nutrition nursing practice knowledge dimension scores, attitude dimension scores, and practice dimension scores of 507 nutritional support specialist nurses were 30.00 (28.00, 31.00) , 47.00 (41.00, 50.00) , (22.65±6.77) , respectively. Multiple linear regression analyses showed that education was an influencing factor in the knowledge dimension of nutrition nursing practice among nutritional support nurse specialists ( P<0.05) ; title, hospital level, and years of experience as a nutritional support nurse specialist were influencing factors in the attitude dimension of nutrition nursing practice ( P<0.05) . Conclusions:Nutritional support specialist nurses have a good knowledge base of nutrition nursing practice and a positive attitude, but their practices need to be further improved. Knowledge, attitude, and practice are affected by multiple factors such as education, title, hospital level, and number of years in the professional field. In the process of nurse specialist training, managers should pay attention to the learning needs of nurses at different levels, carry out targeted training, establish a standard workflow for nurse specialists, and emphasize the construction of talents in primary hospitals, so as to promote the high-quality development of nutrition support specialist nurses.
8.Role and value of nurses in nutritional screening and assessment of hospitalized patients
Yuan XU ; Yanming DING ; Ni YANG ; Ge LIU ; Qian LU ; Ying LIU ; Shuli GUO ; Yufen MA
Chinese Journal of Modern Nursing 2025;31(13):1687-1691
The participation of nurses in nutritional screening and assessment is not only the foundation for achieving full coverage of nutritional screening and assessment for hospitalized patients, but also an important guarantee for preventing and improving adverse clinical outcomes in hospitalized patients. Nurses should start by distinguishing between the concepts of nutritional screening and nutritional assessment, selecting patient-appropriate nutritional screening and assessment tools, and accurately timing nutritional screening and assessment to correctly perform nutritional screening and assessment. At the same time, nurses have a unique role and value in identifying nutritional risks in hospitalized patients, performing nutritional screening and assessment, and multidisciplinary nutritional diagnosis and treatment. Although nurses face many challenges in practice, they can address these challenges through artificial intelligence empowerment, the development of nutritional screening and assessment standard processes, the provision of health education to assist patients in self-management, and the establishment of training systems.
9.Comparative study of cardiac morphology, size and function between fetuses with tetralogy of Fallot and fetuses with malalignment ventricular septal defect and pulmonary stenosis by multi-parameter quantitative echocardiography
Shuli YANG ; Bowen ZHAO ; Mei PAN ; Xiaohui PENG ; Ran CHEN ; Yuanshi TIAN ; Min DI ; Heqing GUO
Chinese Journal of Ultrasonography 2025;34(2):139-148
Objective:To analyze the differences in heart size,shape and function between fetuses with tetralogy of Fallot(TOF)and fetuses with malalignment ventricular septal defect(VSD)and pulmonary stenosis(PS)(named as,mild TOF)by fetal heart quantification(fetal HQ)and multi-parameter fetal echocardiography.Methods:From June 2021 to June 2023,50 fetuses with TOF(TOF group)diagnosed by fetal echocardiography at the Department of Diagnostic Ultrasound & Echocardiography Sir Run Run Shaw Hospital,Zhejiang University College of Medicine and 34 fetuses with VSD and PS matched to gestational age(mild TOF group)were retrospectively selected. Cardiovascular parameters were measured by 2D echocardiography,M-mode echocardiography and fetal HQ,including aortic dimension(AO)and its Z-score(AO Z-score),pulmonary artery diameter(PA)and its Z-score(PA Z-score),PA/AO ratio,main pulmonary artery diameter(MPA)and its Z-score(MPA Z-score),left pulmonary artery diameter(LPA)and its Z-score(LPA Z-score),right pulmonary artery diameter(RPA)and its Z-score(RPA Z-score),McGoon index(MGI),tricuspid annular diameter(TV)and its Z-score(TV Z-score),mitral annular diameter(MV)and its Z-score(MV Z-score),and MV/TV ratio. Measurements of global ventricular morphologic parameters included cardiac axis,left and right ventricular transverse diameters(LVW,RVW)and their ratio(LVW/RVW),left and right ventricular long diameters(LVL,RVL)and LVL/RVL ratio,left and right ventricular areas(LVA,RVA)and LVA/RVA ratio,global spherical index(GSI)and its Z-score,four chamber view transverse diameter(4CV-Width-ED),four chamber view end-diastolic longitudinal diameter(4CV-Length-ED),four chamber view end-diastolic area(4CV-Area-ED). Measurements of left and right global ventricular functional parameters included fractional left ventricular and right ventricular area changes(LVFAC,RVFAC),left ventricular ejection fraction(LVEF),left ventricular and right ventricular global longitudinal strains(LVGLS,RVGLS);end diastolic width diameter(Width-ED),SI and fractional shortening rate(FS)of 24 segments of left and right ventricles. The differences of the above parameters between the two groups were analyzed and compared,and the relationships between absolute values of GLS in left and right ventricles of TOF fetus and PA Z-score,MPA Z-score and PA/AO were analyzed. Binary Logistic regression model was used to select the best variables,and ROC curve was adopted to analyze the predictive values of ultrasonic parameter variables on TOF.Results:There were statistically significant differences in MV,TV,RVW,RVL,LVL,LVA,RVA,4CV-Length-ED,LVGLS,RVGLS,RVFAC,PA/AO,MPA,RPA,LPA,MGI,PA and PA Z-score between TOF group and mild TOF group(all P<0.05). The Width-ED values of all segments of left ventricle were statistically different between TOF group and mild TOF group(all P<0.05). There were statistical differences in SI between LV segments 4~6 and 8~24,and RV segments 1~21(all P<0.05). The FS values between the 8th and 10th to 18th segments of RV revealed statistical differences(all P<0.05). There were no statistical differences in the other parameters(all P>0.05). The absolute value of LVGLS in TOF fetuses was positively correlated with PA Z-score,MPA Z-score and PA/AO( r = 0.313,0.344,0.304,all P<0.05),and the absolute value of RVGLS was positively correlated with PA Z-score,MPA Z-score,and PA/AO( r = 0.323,0.334,0.357,all P<0.05). Binary Logistic regression model analysis confirmed that LVGLS,RVFAC and PA/AO were predictive variables. ROC curve analysis showed that the areas under the curves of LVGLS,RVFAC and PA/AO for predicting TOF were 0.746,0.693 and 0.849 respectively. The combined prediction efficiency was higher,and the area under the curve was 0.906. Conclusions:Fetal HQ combined with multiple fetal echocardiographic quantification indices can evaluate the differences in fetal heart size,shape and function between TOF and mild TOF. It is expected to provide important reference information in prenatal diagnosis and consultation for fetuses with TOF and mild TOF.
10.Antitumor immune response of stimulator of interferon genes-based Dickkopf-related protein 1-targeted vaccine in multiple myeloma
Pengli XIAO ; Shuli GUO ; Huirui WANG ; Huiyun MAO ; Wanhua AN
Journal of Xinxiang Medical College 2024;41(10):911-918
Objective To explore whether stimulator of interferon genes(STING)agonist ADU-S100 could enhance the antitumor immune response of a chitosan(CS)nanoparticle-mediated DNA vaccine containing a tumor-specific antigen Dickkopf-related protein 1(DKK1)in multiple myeloma(MM).Methods CS-DNA nanoparticles were prepared by using the compound coprecipitation method.The particle sizes and Zeta potential of the CS-DNA nanoparticles were measured by using the Zetasizer Nano-ZS laser particle size analyzer.The DNA protection effect and in vivo DNA expression efficiency of the CS-DNA nanoparticles were assessed by using gel retardation assay and Western blot,respectively.The lentiviruses expressing human DKK1(hDKK1)genes were used to establish MPC-11 cells(MPC-11-hDKK1)which stably expressed hDKK1,and the MPC-11-hDKK1 cells were subcutaneously given to mice to construct tumor models.The tumor-bearing mice were randomly divided into a control group(intramuscular injection of CS-pcDNA3.1),an ADU-S100 immunization group(subcutaneous injection of ADU-S100),a CS-pDKK1 immunization group(intramuscular injection of CS-pDKK1)and an ADU-S1OO/CS-pDKK1 co-immunization group(intramuscular injection of CS-pDKK1+subcutaneous injection of ADU-S100),with 5 mice in each group.The tumor-bearing mice in each group were immunized 3 times at 10-day intervals according to the corresponding immunization schedule.The size of tumor was measured every week.On day 42 after MPC-11-hDKK1 cell inoculation,the tumor weight of mice in each immunization group was measured;the percentages of CD11c+dendritic cell(DC),CD8+CD11c+DC and major histocompatibility complex class Ⅱ(MHCII)+CD11c+DC subsets in the spleen of mice in each immunization group were detected by using flow cytometry.The splenocytes of mice in each group were stimulated with recombinant hDKK-1 protein in vitro,the percentage of EdU+cells in CD8+T lymphocytes in each immunization group was detected by using flow cytometry,and the killing effect of cytotoxic T lymphocyte(CTL)in each group was assessed by using the lactate dehydrogenase(LDH)cytotoxicity assay kit.Results The particle size and Zeta potential of the CS-DNA nanoparticles were(204.3±2.31)nm and(15.47±1.01)mV,respectively.Gel retardation assay showed that DNA enveloped in CS nanoparticles could be completely retarded.Western blot analysis indicated that CS-DNA nanoparticles could be effectively expressed in vivo.The relative expression of DKK1 protein was significantly higher in MPC-11-hDKK1 cells than in MPC-11-Ctrl cells(P<0.05).On days 7 and 14 after MPC-11-hDKK1 cell inoculation,there was no significant difference in tumor volume of mice between the ADU-S100 immunization group,CS-pDKK1 immunization group,ADU-S100/CS-pDKK1 co-immunization group and the control group(P>0.05);on days 21,28,35 and 42 after MPC-11-hDKK1 cell inoculation,the tumor volumes of mice in the ADU-S100 immunization group,CS-pDKK1 immunization group and ADU-S100/CS-pDKK1 co-immunization group were significantly lower than those in the control group(P<0.05);the tumor volume of mice in the ADU-S100/CS-pDKK1 co-immunization group was significantly lower than that in the ADU-S100 immunization group and CS-pDKK1 immunization group(P<0.05).On day 42 after MPC-11-hDKK1 cell inoculation,the tumor weight of mice in the ADU-S100 immunization group,CS-pDKK1 immunization group and ADU-S1 OO/CS-pDKK1 co-immunization group was significantly lower than that in the control group(P<0.05);the tumor weight of mice in the ADU-S100/CS-pDKK1 co-immunization group was significantly lower than that in the ADU-S100 immunization group and CS-pDKK1 immunization group(P<0.05).The proportions of CD11c+DC,CD8+CD11c+DC and MHCII+CD11c+DC subsets in the spleen of mice in the ADU-S100 immunization group,CS-pDKK1 immunization group and ADU-S100/CS-pDKK1 co-immunization group were significantly higher than those in the control group(P<0.05).The proportions of CD11c+DC,CD8+CD11c+DC and MHCII+CD11c+DC subsets in the spleen of mice in the ADU-S100/CS-pDKK1 co-immunization group were significantly higher than those in the ADU-S100 immunization group and CS-pDKK1 immunization group(P<0.05).The CTL killing effect and the proportion of EdU+cells in CD8+T lymphocytes in the ADU-S100 immunization group,CS-pDKK1 immunization group and ADU-S1OO/CS-pDKK1 co-immunization group were significantly higher than those in the control group(P<0.05);the CTL killing effect and the proportion of EdU+cells in CD8+T lymphocytes in the ADU-S100/CS-pDKK1 co-immunization group were significantly higher than those in the ADU-S100 immunization group and CS-pDKK1 immunization group(P<0.05).Conclusion STING agonist ADU-S100 can significantly improve the antitumor immunity of the CS-pDKK1 nanoparticle vaccine in MM,and this vaccine strategy provides a potential treatment approach for MM.

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