1.Role of MYADM in the cholesterol mediated proliferation and metastasis of lung adenocarcinoma
Yuan ZHAO ; Lizhen ZHANG ; Guangdong CHENG ; Yawei SUN ; Jinben MA ; Yanliang LIN
Chinese Journal of Oncology 2025;47(11):1080-1093
Objective:To explore the role and related mechanism of myeloid related differentiation markers (MYADM) in lung adenocarcinoma metastasis induced by high cholesterol diet.Methods:(1) Cell experiments: Using lung adenocarcinoma A549 and H1975 cells, the cells were treated with 0.8 mg/ml cholesterol and then transfected with a lentivirus to knock down MYADM. The overexpression of MYADM was achieved by transfecting the cells with an overexpression plasmid. Western blotting was used to detect the expression levels of MYADM, E-cadherin, β-catenin, MMP-2, MMP-9, and vimentin in the cells. The proliferation ability of the cells was assessed using the plate clonal formation assay, while the migration and invasion ability were evaluated using the Transwell assay. Western blot was used to determine the effects of MYADM knockdown or overexpression on these proteins. Western blot and immunofluorescence assays were conducted to investigate the impact of Akt phosphorylation on the expression of MYADM and Rac1 in cholesterol-treated lung adenocarcinoma cells, as well as the phosphorylation of c-Myc. Western blot was also used to assess the effect of c-Myc knockdown on the expression of MYADM and MCT1 in lung adenocarcinoma cells. Chromatin immunoprecipitation (ChIP) assays were performed to investigate the impact of cholesterol on the binding between c-Myc and the promoters of MYADM and MCT1 in lung adenocarcinoma cells. (2) Animal experiment: A549 cells or A549 cells with MYADM knockdown were intravenously inoculated into BALB/c nude mice, which were then divided into a normal diet group and a high cholesterol diet group. Using a live imaging system, the growth and metastasis of tumors in the mice were monitored. After 42 days, lung tissues were collected for immunohistochemical staining to detect changes in relevant proteins.Results:After cholesterol treatment, the expression level of MYADM in A549 cells increased from 1.00±0.18 to 3.28±0.28 ( P<0.001), and in H1975 cells, it increased from 1.00±0.06 to 2.03±0.10 ( P<0.001). Compared with the control group, the expression of E-cadherin in lung adenocarcinoma cells after MYADM knockdown increased ( P<0.01), while the expressions of β-catenin, MMP-2, MMP-9, and vimentin decreased (all P<0.01). After MYADM knockdown, the number of clonal plates decreased in A549 cells (203±23 vs 60±18, t=8.48, P=0.001) and H1975 cells (298±64 vs 137±51, t=3.41, P=0.271). The number of invasive cells also decreased in A549 cells (212±18 vs 99±34, t=5.09, P=0.007) and H1975 cells (268±34 vs 134±14, t=6.31, P=0.003). Additionally, the number of migratory cells decreased in A549 cells (353±37 vs 124±29, t=8.44, P=0.001) and H1975 cells (279±41 vs 79±19, t=7.67, P=0.002). In the lung adenocarcinoma cells overexpressing MYADM, the expression of E-cadherin decreased ( P<0.01), while the levels of β-catenin, MMP-2, MMP-9, and vimentin increased (all P<0.01). The number of plate clonal colonies formed by lung adenocarcinoma cells overexpressing MYADM increased significantly in A549 cells, (94±26 vs 298±34, t=8.26, P=0.001) and H1975 cells (83±13 vs 331±24, t=15.74, P<0.001). The number of invasive A549 cells also increased (118±17 vs 193±24, t=4.41, P=0.012) and (156±19 vs 321±12, t=12.72, P<0.001). Additionally, the number of migrating cells increased in A549 cells (171±22 vs 284±15, t=7.35, P=0.002) and in H1975 cells (178±7 vs 263±12, t=10.6, P<0.001). Experiments related to the molecular mechanism showed that overexpression of MYADM promotes the expression of MCT1 in lung adenocarcinoma cells (all P<0.01). Cholesterol not only enhances the expression of MYADM in lung adenocarcinoma cells, but also boosts the expression of Rac1 and MCT1, as well as the phosphorylation of Akt and c-Myc (all P<0.05). Immunoprecipitation experiments revealed that in A549 cells treated with cholesterol, MYADM-Rac1 interaction levels increased from (100.0±15.9)% to (191.0±26.7)% ( P=0.007), while in H1975 cells, the levels increased from (100.0±18.2)% to (170.0±27.5)% ( P=0.021). ChIP confirmed that cholesterol treatment enhances the binding of c-Myc to the promoters of MYADM and MCT1. In vivo experiments demonstrated that a high-cholesterol diet promotes the metastasis of lung adenocarcinoma cells in mice, inducing the expression of MYADM, MCT1, and Rac1, as well as the phosphorylation of Akt and c-Myc in mouse lung tissue. Conversely, knocking down MYADM inhibits the metastasis of lung adenocarcinoma cells in mice, suppressing the expression of MYADM, MCT1, and Rac1, as well as the phosphorylation of Akt and c-Myc in mouse lung tissues. Conclusion:Cholesterol may induce lung adenocarcinoma cells proliferation and metastasis by regulating the MYADM/Rac1/Akt/c-Myc/MCT1 axis.
2.Causal relationship between type 2 diabetes mellitus and cognitive impairment based on Mendelian randomization
Yijia LIN ; Lizhen CHENG ; Tingjun HU ; Ya MIAO
Journal of Shanghai Jiaotong University(Medical Science) 2025;45(2):204-210
Objective·To investigate the causal relationship between type 2 diabetes mellitus(T2DM)and cognitive dysfunction using two-sample Mendelian randomisation(MR).Methods·Instrumental variables associated with T2DM were pooled from a large-scale genome-wide association study(GWAS)dataset.Inverse variance weighting was used as the primary analytical technique,supplemented by MR-Egger regression,weighted median and simple median analyses.Meta-analysis was jointly applied to combine different endpoints and to analyse the possibility of a causal relationship between T2DM and dementia,Alzheimer's disease,and Parkinson's dementia.Horizontal pleiotropy was examined by MR-PRESSO global test and MR-Egger analysis.Results·There was a causal relationship between genetically predicted T2DM and dementia(OR=1.11,95%CI 1.02~1.20,P=1.96×10-2)and AD(OR=1.16,95%CI 1.04~1.30,P=8.41×10-3).Meta-analysis also supported the association between T2DM and cognitive impairment(OR=1.12,95%CI 1.05~1.20,P=4.22×10-4).A series of sensitivity analyses suggested the absence of heterogeneity and horizontal pleiotropy.Reverse MR analysis showed no significant causal relationship of various types of dementia on T2DM.Conclusion·T2DM is positively associated with the risk of developing various types of dementia,suggesting that T2DM may be an important risk factor for cognitive impairment.
3.Analysis of the effectiveness of technology transfer of research-oriented hospital:a case study of an af-filiated hospital of a university in Guangdong province
Yi WEI ; Shiying CHEN ; Lizhen LI ; Cuiwei CHEN ; Guiping LIN ; Xiuying CUI
Modern Hospital 2025;25(1):143-147
Objective This study aims to explore effective approaches for the transfer of medical scientific and techno-logical achievements to promote the development of research-oriented hospitals.Methods The technology transfer achievements of an affiliated hospital of a university in Guangdong Province over the past six years(2018-2023)were statistically analyzed.The challenges faced during the transfer process,the measures taken,and the current achievements were discussed.Results The number of patent authorizations and authorized departments in the hospital has increased year by year.The transfer rate has risen from 0%in 2019 to 6.69%in 2023.Currently,46 projects have been successfully transferred,with a total transfer amount exceeding 30 million yuan,indicating significant effectiveness in the transfer of medical scientific and technological achievements.Conclusion The hospital attaches great importance to and overall manages the transfer process,establishing a sound manage-ment structure,improving incentive and support systems,and regularly conducting special lectures,training,and guidance.These efforts guide researchers to start from clinical problems and ultimately serve clinical diagnosis and treatment,creating a fa-vorable environment for technology transfer,improving the transfer rate,and promoting the development of research-oriented hos-pitals.
4.Causal relationship between type 2 diabetes mellitus and cognitive impairment based on Mendelian randomization
Yijia LIN ; Lizhen CHENG ; Tingjun HU ; Ya MIAO
Journal of Shanghai Jiaotong University(Medical Science) 2025;45(2):204-210
Objective·To investigate the causal relationship between type 2 diabetes mellitus(T2DM)and cognitive dysfunction using two-sample Mendelian randomisation(MR).Methods·Instrumental variables associated with T2DM were pooled from a large-scale genome-wide association study(GWAS)dataset.Inverse variance weighting was used as the primary analytical technique,supplemented by MR-Egger regression,weighted median and simple median analyses.Meta-analysis was jointly applied to combine different endpoints and to analyse the possibility of a causal relationship between T2DM and dementia,Alzheimer's disease,and Parkinson's dementia.Horizontal pleiotropy was examined by MR-PRESSO global test and MR-Egger analysis.Results·There was a causal relationship between genetically predicted T2DM and dementia(OR=1.11,95%CI 1.02~1.20,P=1.96×10-2)and AD(OR=1.16,95%CI 1.04~1.30,P=8.41×10-3).Meta-analysis also supported the association between T2DM and cognitive impairment(OR=1.12,95%CI 1.05~1.20,P=4.22×10-4).A series of sensitivity analyses suggested the absence of heterogeneity and horizontal pleiotropy.Reverse MR analysis showed no significant causal relationship of various types of dementia on T2DM.Conclusion·T2DM is positively associated with the risk of developing various types of dementia,suggesting that T2DM may be an important risk factor for cognitive impairment.
5.Analysis of the effectiveness of technology transfer of research-oriented hospital:a case study of an af-filiated hospital of a university in Guangdong province
Yi WEI ; Shiying CHEN ; Lizhen LI ; Cuiwei CHEN ; Guiping LIN ; Xiuying CUI
Modern Hospital 2025;25(1):143-147
Objective This study aims to explore effective approaches for the transfer of medical scientific and techno-logical achievements to promote the development of research-oriented hospitals.Methods The technology transfer achievements of an affiliated hospital of a university in Guangdong Province over the past six years(2018-2023)were statistically analyzed.The challenges faced during the transfer process,the measures taken,and the current achievements were discussed.Results The number of patent authorizations and authorized departments in the hospital has increased year by year.The transfer rate has risen from 0%in 2019 to 6.69%in 2023.Currently,46 projects have been successfully transferred,with a total transfer amount exceeding 30 million yuan,indicating significant effectiveness in the transfer of medical scientific and technological achievements.Conclusion The hospital attaches great importance to and overall manages the transfer process,establishing a sound manage-ment structure,improving incentive and support systems,and regularly conducting special lectures,training,and guidance.These efforts guide researchers to start from clinical problems and ultimately serve clinical diagnosis and treatment,creating a fa-vorable environment for technology transfer,improving the transfer rate,and promoting the development of research-oriented hos-pitals.
6.Role of MYADM in the cholesterol mediated proliferation and metastasis of lung adenocarcinoma
Yuan ZHAO ; Lizhen ZHANG ; Guangdong CHENG ; Yawei SUN ; Jinben MA ; Yanliang LIN
Chinese Journal of Oncology 2025;47(11):1080-1093
Objective:To explore the role and related mechanism of myeloid related differentiation markers (MYADM) in lung adenocarcinoma metastasis induced by high cholesterol diet.Methods:(1) Cell experiments: Using lung adenocarcinoma A549 and H1975 cells, the cells were treated with 0.8 mg/ml cholesterol and then transfected with a lentivirus to knock down MYADM. The overexpression of MYADM was achieved by transfecting the cells with an overexpression plasmid. Western blotting was used to detect the expression levels of MYADM, E-cadherin, β-catenin, MMP-2, MMP-9, and vimentin in the cells. The proliferation ability of the cells was assessed using the plate clonal formation assay, while the migration and invasion ability were evaluated using the Transwell assay. Western blot was used to determine the effects of MYADM knockdown or overexpression on these proteins. Western blot and immunofluorescence assays were conducted to investigate the impact of Akt phosphorylation on the expression of MYADM and Rac1 in cholesterol-treated lung adenocarcinoma cells, as well as the phosphorylation of c-Myc. Western blot was also used to assess the effect of c-Myc knockdown on the expression of MYADM and MCT1 in lung adenocarcinoma cells. Chromatin immunoprecipitation (ChIP) assays were performed to investigate the impact of cholesterol on the binding between c-Myc and the promoters of MYADM and MCT1 in lung adenocarcinoma cells. (2) Animal experiment: A549 cells or A549 cells with MYADM knockdown were intravenously inoculated into BALB/c nude mice, which were then divided into a normal diet group and a high cholesterol diet group. Using a live imaging system, the growth and metastasis of tumors in the mice were monitored. After 42 days, lung tissues were collected for immunohistochemical staining to detect changes in relevant proteins.Results:After cholesterol treatment, the expression level of MYADM in A549 cells increased from 1.00±0.18 to 3.28±0.28 ( P<0.001), and in H1975 cells, it increased from 1.00±0.06 to 2.03±0.10 ( P<0.001). Compared with the control group, the expression of E-cadherin in lung adenocarcinoma cells after MYADM knockdown increased ( P<0.01), while the expressions of β-catenin, MMP-2, MMP-9, and vimentin decreased (all P<0.01). After MYADM knockdown, the number of clonal plates decreased in A549 cells (203±23 vs 60±18, t=8.48, P=0.001) and H1975 cells (298±64 vs 137±51, t=3.41, P=0.271). The number of invasive cells also decreased in A549 cells (212±18 vs 99±34, t=5.09, P=0.007) and H1975 cells (268±34 vs 134±14, t=6.31, P=0.003). Additionally, the number of migratory cells decreased in A549 cells (353±37 vs 124±29, t=8.44, P=0.001) and H1975 cells (279±41 vs 79±19, t=7.67, P=0.002). In the lung adenocarcinoma cells overexpressing MYADM, the expression of E-cadherin decreased ( P<0.01), while the levels of β-catenin, MMP-2, MMP-9, and vimentin increased (all P<0.01). The number of plate clonal colonies formed by lung adenocarcinoma cells overexpressing MYADM increased significantly in A549 cells, (94±26 vs 298±34, t=8.26, P=0.001) and H1975 cells (83±13 vs 331±24, t=15.74, P<0.001). The number of invasive A549 cells also increased (118±17 vs 193±24, t=4.41, P=0.012) and (156±19 vs 321±12, t=12.72, P<0.001). Additionally, the number of migrating cells increased in A549 cells (171±22 vs 284±15, t=7.35, P=0.002) and in H1975 cells (178±7 vs 263±12, t=10.6, P<0.001). Experiments related to the molecular mechanism showed that overexpression of MYADM promotes the expression of MCT1 in lung adenocarcinoma cells (all P<0.01). Cholesterol not only enhances the expression of MYADM in lung adenocarcinoma cells, but also boosts the expression of Rac1 and MCT1, as well as the phosphorylation of Akt and c-Myc (all P<0.05). Immunoprecipitation experiments revealed that in A549 cells treated with cholesterol, MYADM-Rac1 interaction levels increased from (100.0±15.9)% to (191.0±26.7)% ( P=0.007), while in H1975 cells, the levels increased from (100.0±18.2)% to (170.0±27.5)% ( P=0.021). ChIP confirmed that cholesterol treatment enhances the binding of c-Myc to the promoters of MYADM and MCT1. In vivo experiments demonstrated that a high-cholesterol diet promotes the metastasis of lung adenocarcinoma cells in mice, inducing the expression of MYADM, MCT1, and Rac1, as well as the phosphorylation of Akt and c-Myc in mouse lung tissue. Conversely, knocking down MYADM inhibits the metastasis of lung adenocarcinoma cells in mice, suppressing the expression of MYADM, MCT1, and Rac1, as well as the phosphorylation of Akt and c-Myc in mouse lung tissues. Conclusion:Cholesterol may induce lung adenocarcinoma cells proliferation and metastasis by regulating the MYADM/Rac1/Akt/c-Myc/MCT1 axis.
7.Correlation of changes in serum T lymphocyte subsets levels with disease severity and prognosis in patients with ankylosing spondylitis
Lizhen CHEN ; Jinxing SHI ; Xiaolin LIU ; Shengjie XU ; Wenping LIN
Journal of Xi'an Jiaotong University(Medical Sciences) 2024;45(5):769-775
Objective To study the changes in peripheral blood T lymphocytes in patients with ankylosing spondylitis and their correlation with the disease's severity and prognosis.Methods We selected 120 patients with ankylosing spondylitis treated between January 2020 and March 2023 as the research group and 120 healthy people who had medical examinations in the same period as the health group.We detected the changes in CD4+,CD8+and CD4+/CD8+values of peripheral blood T lymphocyte subsets with flow cytometry,compared the differences in T lymphocyte subsets between the two groups,and analyzed the correlation with the disease severity of the patients.All the 120 patients with ankylosing spondylitis were followed up for 6 months after treatment to assess their prognosis.General information and T lymphocyte sub-groups CD4+,CD8+level,CD4+/CD8+value changes were compared among patients with different prognosis.We analyzed the value of T lymphocyte sub-groups in predicting the prognosis of patients with ankylosing spondylitis.Results In the research group CD4+and CD4+/CD8+were lower but CD8 1 was higher than those in the healthy group(P<0.05).CD4+and CD4+/CD8 were lower but CD8+was higher in patients with advanced ankylosing spondylitis than in early and mid-term patients(P<0.05).The ROC curve analysis showed that the AUC of CD4+,CD8+,and CD4+/CD8+combined diagnosis of ankylosing spondylitis patients was 0.878,with higher diagnostic sensitivity than that of the single diagnosis(P<0.05).In the poor prognosis group,CD8+was higher than that in the excellent prognosis group,but CD4+and CD4+/CD8 value were lower than the latter(P<0.05).The results of Pearson test showed that CD4+and CD4+/CD8+were negatively correlated with the prognosis of patients with ankylosing spondylitis(r=-0.568,-0.656,P<0.001).CD8+was positively correlated with the prognosis of patients with ankylosing spondylitis(r=0.623,P<0.001).ROC curve analysis showed that the AUC of the combined diagnosis of CD4+,CD8+and CD4+/CD8+for ankylosing spondylitis patients was 0.910,and the diagnostic sensitivity was higher than that of single diagnosis(P<0.05).Conclusion The abnormal levels of peripheral blood T lymphocyte subsets in patients with ankylosing spondylitis are closely related to the severity and prognosis of the disease,and can be used as a reference indicator for diagnosing the severity and prognosis of ankylosing spondylitis.
8.Synthesis of 177Lu-labeled liquid metal-based ROS radiosensitizer and preliminary study of its therapeutic efficacy on breast cancer in mice
Junjie YAN ; Chen SU ; Jianhan LIN ; Xinyu WANG ; Donghui PAN ; Yuping XU ; Lizhen WANG ; Chongyang CHEN ; Min YANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(6):343-348
Objective:To radiolabel hyperbranched polymer (HG)-modified liquid metal nanodroplet (LMND)@HG with 177Lu, and explore the radiotherapy sensitization effect on anti-breast cancer therapy. Methods:The ultrasonication method was used to prepare LMND@HG, and then 177LuCl 3 was mixed with LMND@HG to label 177Lu by alloying reactions. The labeling rate, plasma stability and cytotoxicity of 177Lu-LMND@HG were detected. Xenograft mouse model of breast cancer was constructed, and the tumor inhibition test was performed by an intratumoral injection. The tumor progression was monitored by in vivo imaging system. The mechanism of tumor inhibition was verified by immunohistochemistry and immunofluorescence assays. One-way analysis of variance, repeated measures analysis of variance, and the least significant difference t test were used to analyze the data. Results:177Lu was successfully labeled to LMND@HG with a high labeling efficiency >95%. The product did not require further purification and the plasma radiochemical purity was still higher than 95% after 5 d. The cytotoxicity test showed that a dose of 888 kBq (40 mg/L) 177Lu-LMND@HG had obvious toxicity to 4T1 cells, which was significantly lower than 177LuCl 3 (cell viabilities: (16.48±7.81)% vs (85.77±8.87)%; F=77.81, t=11.73, P<0.001) and LMND@HG ((46.53±5.75)%; t=6.20, P<0.001). The biological distribution results showed that 177Lu-LMND@HG was mainly distributed in tumor tissue 5 d after intratumoral injection. The results of the tumor inhibition experiment showed that 1.48 MBq 177Lu-LMND@HG could significantly inhibit the tumor growth compared with the 177LuCl 3 (tumor volume: (222.66±97.70) vs (789.13±245.04) mm 3;F=18.55, t=4.29, P=0.005). In vivo optical imaging of small animals showed that 1.48 MBq and 3.70 MBq 177Lu-LMND@HG both significantly inhibited the tumor growth. Immunofluorescence and immunohistochemical results showed that 177Lu-LMND@HG caused double-stranded DNA break, and suppressed the tumor growth by inhibiting cell proliferation and angiogenesis. Conclusions:A novel 177Lu-liquid metal-based reactive oxygen species (ROS) radiation sensitizer is successfully prepared in this study. The preparation method is efficient and convenient, and the product has high stability. 177Lu-LMND@HG shows an obvious radiotherapy sensitization effect on breast tumor-bearing mice.
9.Effect of health education based on LEARNS model on urinary incontinence patients after laparoscopic radical prostatectomy
Jing XU ; Qingxian KE ; Limin HUANG ; Xiaoying LIU ; Lizhen LIN
China Modern Doctor 2024;62(34):46-49
Objective To explore the effect of health education based on LEARNS model in patients with urinary incontinence after laparoscopic radical prostatectomy. Methods A total of 76 patients with urinary incontinence after laparoscopic radical prostatectomy admitted to Fujian Cancer Hospital from February 2022 to December 2023 were selected and divided into control group and observation group according to random number table method,with 38 cases in each group. Patients in control group received routine health education,while patients in observation group received health education based on LEARNS model. Both groups were intervened for one month. Urinary control ability,pelvic floor muscle training knowledge level,pelvic floor muscle training accuracy rate and quality of life of two groups were compared before and after intervention. Results After the intervention,International Consultation on Incontinence questionnaire-urinary incontinence short form (ICIQ-UI SF) scores of patients in both groups were significantly lower than before intervention,and scores of pelvic floor muscle training knowledge questionnaire and 36-item short form health survey (SF-36) were significantly higher than before intervention (P<0.05). The ICIQ-UI SF score of observation group was significantly lower than that of control group,and the scores of pelvic floor muscle training knowledge questionnaire and SF-36 were significantly higher than those of control group (P<0.05). The correct rate of pelvic floor muscle training in observation group was significantly higher than that in control group (92.11% vs. 68.42%,x2=6.727,P=0.009). Conclusion Health education based on LEARNS model can effectively improve the knowledge level and correct rate of pelvic floor muscle training of urinary incontinence patients after radical prostatectomy,improve the urinary control ability and quality of life of patients.
10.Effect of health education based on LEARNS model on urinary incontinence patients after laparoscopic radical prostatectomy
Jing XU ; Qingxian KE ; Limin HUANG ; Xiaoying LIU ; Lizhen LIN
China Modern Doctor 2024;62(34):46-49
Objective To explore the effect of health education based on LEARNS model in patients with urinary incontinence after laparoscopic radical prostatectomy. Methods A total of 76 patients with urinary incontinence after laparoscopic radical prostatectomy admitted to Fujian Cancer Hospital from February 2022 to December 2023 were selected and divided into control group and observation group according to random number table method,with 38 cases in each group. Patients in control group received routine health education,while patients in observation group received health education based on LEARNS model. Both groups were intervened for one month. Urinary control ability,pelvic floor muscle training knowledge level,pelvic floor muscle training accuracy rate and quality of life of two groups were compared before and after intervention. Results After the intervention,International Consultation on Incontinence questionnaire-urinary incontinence short form (ICIQ-UI SF) scores of patients in both groups were significantly lower than before intervention,and scores of pelvic floor muscle training knowledge questionnaire and 36-item short form health survey (SF-36) were significantly higher than before intervention (P<0.05). The ICIQ-UI SF score of observation group was significantly lower than that of control group,and the scores of pelvic floor muscle training knowledge questionnaire and SF-36 were significantly higher than those of control group (P<0.05). The correct rate of pelvic floor muscle training in observation group was significantly higher than that in control group (92.11% vs. 68.42%,x2=6.727,P=0.009). Conclusion Health education based on LEARNS model can effectively improve the knowledge level and correct rate of pelvic floor muscle training of urinary incontinence patients after radical prostatectomy,improve the urinary control ability and quality of life of patients.

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