1.The comprehensive assessment tools for senile dementia: a systematic review based on COSMIN methodology
Yiping FANG ; Yun ZHANG ; Xiuyuan ZHU ; Jingling LI ; Ning LIU
Chinese Journal of Practical Nursing 2024;40(25):1929-1939
		                        		
		                        			
		                        			Objective:To assess the methodological and measurement quality of comprehensive assessment tools for evaluating senile dementia, in order to provide evidence-based guidance for clinical selection of the best assessment tool.Methods:Manually searched CNKI, Wanfang Database, VIP Database, SinoMed, PubMed, Embase, Web of Science, Cochrane Library, CINAHL, ProQuest, Ovid and Scopus databases to collect and evaluate comprehensive assessment tool measurements forsenile dementia. For research on academic attributes, the search time limit was from the establishment of the database to January 4th, 2024. Two researchers independently screened the literature and extracted information, used the COSMIN guidelines to evaluate the included assessment tools, and formed final recommendations.Results:A total of 14 articles were included, including 9 comprehensive assessment tools for the elderly with dementia. Among them, the Care Needs Assessment Scale for Alzheimer′s Disease Patients had moderate and above evidence proving that its content validity and internal consistency were "sufficient", so it was a category A strong recommendation. The remaining 8 evaluation tools were all category B recommendations.Conclusions:Among the existing comprehensive assessment tools for the elderly with dementia, the Care Needs Assessment Scale for Alzheimer′s Disease Patients has good reliability and validity. This scale has 4 dimensions and 16 items. However, there are uncertainties and unmentioned measurement properties of the scale in terms of cross-cultural validity/measurement equivalence, stability, measurement error, hypothesis testing, calibration validity, and responsiveness. More evidence is needed in the future to further comprehensively validate and improve it, providing a basis for selecting a more effective, comprehensive and high-quality comprehensive assessment tool for the elderly with dementia.
		                        		
		                        		
		                        		
		                        	
2.Influencing factors of depressive symptoms among rural elderly patients with chronic diseases
WU Shaofeng ; WANG Suzhen ; ZHU Xiuyuan ; LI Jing ; FENG Meiling ; ZHANG Delin
Journal of Preventive Medicine 2023;35(4):277-281
		                        		
		                        			Objective:
		                        			To investigate the influencing factors of depressive symptoms among rural elderly patients with chronic diseases in China, so as to provide insights into depression prevention and control among the rural elderly patients with chronic diseases.
		                        		
		                        			Methods:
		                        			The basic demographics, health status, and lifestyle of rural residents at ages of 65 years and older who had at least one chronic disease were retrieved from The Chinese Longitudinal Healthy Longevity Survey (CLHLS) database in 2018, and participants' depressive symptoms were assessed with The Center for Epidemiological Studies Depression-10 (CES-D-10) scale. Factors affecting the depressive symptoms were identified with a multivariable logistic regression model. 
		                        		
		                        			Results:
		                        			Totally 5 146 rural elderly patients with chronic diseases were enrolled, including 2 373 men (46.11%) and 2 773 women (53.89%). The prevalence of depressive symptoms was 27.13%. Multivariable logistic regression analysis identified having two and more children (OR=0.614, 95%CI: 0.387-0.975), living alone (OR=1.450, 95%CI: 1.192-1.764), life satisfaction (general, OR=1.933, 95%CI: 1.651-2.264; low, OR=5.366, 95%CI: 3.488-8.254), self-assessed health status (general, OR=2.697, 95%CI: 2.284-3.185; poor, OR=5.338, 95%CI: 4.262-6.685), disability in instrumental activities of daily living (OR=1.592, 95%CI: 1.328-1.908), sleep duration (normal, OR=0.502, 95%CI: 0.429-0.586; too long, OR=0.494, 95%CI: 0.405-0.603), exercise (OR=0.721, 95%CI: 0.607-0.856), watching TV (OR=0.787, 95%CI: 0.664-0.933), and gardening activities (OR=0.781, 95%CI: 0.626-0.975) as factors affecting depressive symptoms among rural elderly patients with chronic diseases.
		                        		
		                        			Conclusions
		                        			The prevalence of depressive symptoms was 27.13% among rural elderly patients with chronic diseases. Number of children, living style, life satisfaction, health status, sleep duration, exercise, watching TV, and gardening activities are associated with the development of depressive symptoms among rural elderly patients with chronic diseases.
		                        		
		                        		
		                        		
		                        	
3.Correlation between memory B cells and bone erosion in rheumatoid arthritis
Li ZHU ; Nan HU ; Jing WANG ; Xiuyuan FENG ; Jing LUO ; Yanhua WANG ; Xiaohong LYU ; Dan PU ; Lan HE
Chinese Journal of Rheumatology 2023;27(3):151-157
		                        		
		                        			
		                        			Objective:To explore the distribution characteristics of memory B cells and its relationship with bone erosion in patients with rheumatoid arthritis (RA), and to further understand the mechanism of B cells in the pathogenesis of RA.Methods:B cell subsets in peripheral blood of 200 RA patients and 50 healthy individuals were detected by flow cytometry. According to the surface markers CD19, CD27 and lgD, B cells were divided into CD19 +CD27 +lgD - switched memory B cells, CD19 +CD27 +lgD + non-switched memory B cells, CD19 +CD27 -lgD - double-negative memory B cells and CD19 +CD27 -lgD + naive B cells. B cells in RA patients with various disease activity score, course of disease and treatment were analyzed. Patients were divided into four groups according to the results of joint ultrasonography, including patients without bone erosion, patients with hand bone erosion, patients with knee bone erosion and patients with hand and knee bone erosion. The relationship between the distribution of B cell subsets, autoantibodies and RA bone erosion were analyzed. Differences between the groups were analyzed by independent-samples t test, Mann-Whitney U test and χ2 test. The analysis of variance, Kruskal-Wallis analysis were used for multi-group comparison, Spearman correlation analysis was also used for correlation analysis. Results:①RA patients showed significantly decreased non-switched memory B cells [(9.5±6.7)% vs (12.1±4.7)%, t=2.46, P=0.015] and increased double negative memory B cells [(3.8±2.5)% vs(2.7±1.3)%, t=-4.74, P<0.001] in comparison to healthy individuals. The percentage of non-switched memory B cells were decreased in RA patients with moderate disease activity [(8.4±4.7 )% vs (12.4±7.5)%, t=3.13, P=0.001] and high disease activity [(7.8±7.6)% vs (12.4±7.5)%, t=3.00, P=0.003] in comparison to those in RA patients who achieved remission. Meanwhile, the na?ve B cells [(70.3±15.0)% vs (63.9±14.6)%, t=-2.15, P=0.034] were increased in RA patients with moderate disease activity. No difference was found in RA patients with different disease courses. Total B cells [(4.8±2.9)% vs (7.2±4.1)%, t=-3.24, P=0.001], non-switched memory B cells (7.6±4.3)% vs (10.0±7.1)%, t=-2.63, P=0.010) in RA patients who received prednisone treatment were decreased, while double-negative memory B cells (4.9±3.0)% vs (3.6±2.3)%, t=-2.79, P=0.006] were increased compared with those in RA patients without prednisone treatment. Non-switched memory B cells was decreased in RA patients with hand and knee erosion compared with RA patients without erosion [6.8%(2.5%, 9.5%) vs 9.7%(5.5%, 17.5%), Z=-2.12, P=0.034]. Double negative memory B cells in subgroup with keen erosion [3.3%(2.7%, 5.0%) vs 2.6%(1.9%, 3.8%), Z=-2.09, P=0.036]as well as with hand and knee erosion [3.9%(2.3%, 5.6%) vs 2.6%(1.9%, 3.8%), Z=-2.41, P=0.016] were higher than those in patients without erosion. In addition, higher serum RF level was found in subgroup RA patients with hand and knee erosion compared with subgroup of RA patients without erosion [141.0 (38.0, 874.0) U/ml vs 53.5 (10.0, 106.0)U/ml, Z=-2.07, P=0.039]. Meanwhile, the positive rate of ACPA in RA patients with bone erosion of hand was significantly higher than that of RA patients without bone erosion [81%(52/64) vs 64%(38/59), χ2=4.44, P=0.043). Conclusions:The results suggest that the increase of double negative memory B cells, the decrease of non-switched memory B cells and higher level of autoantibodies may closely relate to bone erosion of RA, which may be one of the pathogenesis of disability in RA.
		                        		
		                        		
		                        		
		                        	
4.Effects of microRNA-106b on migration and invasion of human malignant pleural mesothelioma cell NCI-H2452
Yanan GAO ; Min ZHANG ; Fangfang ZHANG ; Zhenyu JIA ; Xiuyuan YUAN ; Lijin ZHU
Chinese Journal of Industrial Hygiene and Occupational Diseases 2023;41(9):648-654
		                        		
		                        			
		                        			Objective:To investigate the inhibitory effect of microRNA-106b in the process of migration and invasion of human malignant pleural mesothelioma cell NCI-H2452.Methods:In April 2017, the expression level of miRNA-106b in malignant pleural mesothelioma cells (NCI-H2452, MSTO-211H, NCI-H2052) and normal mesothelial cells MeT-5A was detected and analyzed. Using NCI-H2452 cells as a model, the NCI-H2452 cell model with miRNA-106b overexpression was established by transfecting miRNA-106b mimics. The expression level of miRNA-106b in the cells was detected by real-time fluorescent quantitative PCR. The effect of miRNA-106b on the migration and invasion ability of NCI-H2452 cells was analyzed. The gene expression data of malignant mesothelioma and the downstream target gene data of miRNA-106b in public databases were analyzed to screen the downstream target genes of miRNA-106b in mesothelioma cells that affect cell migration and invasion ability, and to verify the expression of this gene in NCI-H2452 cells with miRNA-106b overexpression.Results:The expression of miRNA-106b in three MPM cells was decreased compared with MeT-5A cells ( P<0.001) . The expression level of miRNA-106b was significantly increased after transfection of miRNA-106b mimics ( P<0.001) . The scratch migration levels of the experimental group were 28.45%±4.37%, 38.12%±4.82% and 50.06%±8.92% at 24h, 31h and 48h, respectively. Compared with the control group, the migration level decreased by 37.48%±2.65%, 49.21%±3.45% and 68.14%±3.81% ( P<0.01) . The number of cell migration and invasion decreased in the experimental group compared with the control group ( P<0.001) . Public databases were used to screen and analyze the possibility that TCF21 gene, as a downstream target gene, could affect the migration and invasion ability of MPM cells. The expression level of TCF21 gene was increased after transfection of miRNA-106b mimics in NCI-H2452 cells ( P=0.009) . Conclusion:MiRNA-106b can inhibit the migration and invasion of NCI-H2452 cells and increase the expression of TCF21 gene.
		                        		
		                        		
		                        		
		                        	
5.Effects of microRNA-106b on migration and invasion of human malignant pleural mesothelioma cell NCI-H2452
Yanan GAO ; Min ZHANG ; Fangfang ZHANG ; Zhenyu JIA ; Xiuyuan YUAN ; Lijin ZHU
Chinese Journal of Industrial Hygiene and Occupational Diseases 2023;41(9):648-654
		                        		
		                        			
		                        			Objective:To investigate the inhibitory effect of microRNA-106b in the process of migration and invasion of human malignant pleural mesothelioma cell NCI-H2452.Methods:In April 2017, the expression level of miRNA-106b in malignant pleural mesothelioma cells (NCI-H2452, MSTO-211H, NCI-H2052) and normal mesothelial cells MeT-5A was detected and analyzed. Using NCI-H2452 cells as a model, the NCI-H2452 cell model with miRNA-106b overexpression was established by transfecting miRNA-106b mimics. The expression level of miRNA-106b in the cells was detected by real-time fluorescent quantitative PCR. The effect of miRNA-106b on the migration and invasion ability of NCI-H2452 cells was analyzed. The gene expression data of malignant mesothelioma and the downstream target gene data of miRNA-106b in public databases were analyzed to screen the downstream target genes of miRNA-106b in mesothelioma cells that affect cell migration and invasion ability, and to verify the expression of this gene in NCI-H2452 cells with miRNA-106b overexpression.Results:The expression of miRNA-106b in three MPM cells was decreased compared with MeT-5A cells ( P<0.001) . The expression level of miRNA-106b was significantly increased after transfection of miRNA-106b mimics ( P<0.001) . The scratch migration levels of the experimental group were 28.45%±4.37%, 38.12%±4.82% and 50.06%±8.92% at 24h, 31h and 48h, respectively. Compared with the control group, the migration level decreased by 37.48%±2.65%, 49.21%±3.45% and 68.14%±3.81% ( P<0.01) . The number of cell migration and invasion decreased in the experimental group compared with the control group ( P<0.001) . Public databases were used to screen and analyze the possibility that TCF21 gene, as a downstream target gene, could affect the migration and invasion ability of MPM cells. The expression level of TCF21 gene was increased after transfection of miRNA-106b mimics in NCI-H2452 cells ( P=0.009) . Conclusion:MiRNA-106b can inhibit the migration and invasion of NCI-H2452 cells and increase the expression of TCF21 gene.
		                        		
		                        		
		                        		
		                        	
6.The impact of CD8 and CTLA-4 expression on histopathological character and survival in mesothelioma
Min YU ; Man YU ; Shibo YING ; Xiuyuan YUAN ; Zhaoqiang JIANG ; Jianlin LOU ; Lijin ZHU ; Xing ZHANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2021;39(2):85-90
		                        		
		                        			
		                        			Objective:To investigate the survival and death risk factors of mesothelioma cases stratified by the expression levels of CD8 and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) , providing new clue to evaluate disease progression and clinical outcome.Methods:This was a retrospective case report, which included 47 clinically and pathologically confirmed mesothelioma cases on November 2016. Their clinical and pathological information, asbestos exposure history and survival data were collected. Infiltrated lymphocyte, 5-methylcytosine (5-mC) , CTLA-4, CD8 and Ki-67 antigen were detected using hematoxylin-eosin staining and immunohistochemistry. Survival time and death risk factors of mesothelioma patients with different CD8 and CTLA-4 protein expression characteristics were analyzed. And analyze the influence of Ki-67 expression on the survival of patients with different CD8 and CTLA-4 protein and gene expression characteristics.Results:Among the 47 cases, 63.8% (30/47) had low/medium level of infiltrated lymphocyte. The immunohistochemistry scores of CTLA-4, CD8, 5-mC and Ki-67 were 92.97 (54.95, 120.65) , 72.41 (36.62, 89.82) , 11.09 (3.40, 52.89) and 5.88 (2.41, 11.48) , respectively. Patients with CD8 high CTLA-4 high had higher 5-mC level than those with CD8 high CTLA-4 low ( P<0.01) . The median survival time of 27 cases was 0.83±0.29 year. The median survival times of those with CD8 high CTLA-4 high and CD8 high CTLA-4 low were 0.58±0.51 year and 0.83±0.30 year, respectively ( P=0.521) . The immunohistochemistry score of Ki-67 ≥5.88 was an independent death risk factor for patients with CD8 high CTLA-4 low ( HR=8.40, P=0.01) . Under different CD8 and CTLA-4 protein expression characteristics, in the patients with CD8 high CTLA-4 low, the median survival times of those with high and low Ki-67 expression were 0.57±0.11 years and 2.31±0.46 years, respectively ( P<0.01) . Under different CD8 and CTLA-4 mRNA expression characteristics, in the patients with CD8 high CTLA-4 low, the median survival times of those with high and low Ki-67 mRNA expression were 1.20±0.36 years and 3.38±0.43 years, respectively ( P=0.018) . Conclusion:Mesothelioma case with high CD8 but low CTLA-4 content might coexist DNA hypomethylation. In the presence of high Ki-67 expression, their survival time appears to be shortened with increased death risk.
		                        		
		                        		
		                        		
		                        	
7.Expression and clinical significance of SETD2 in maligant pleural mesothelioma
Man YU ; Min YU ; Lijin ZHU ; Xiuyuan YUAN ; Xing ZHANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2021;39(2):91-98
		                        		
		                        			
		                        			Objective:To analyze the gene mutation profile in malignant pleural mesothelioma (MPM) and investigate the expression of high-frequency mutant genes and its relationship with clinicopathological parameters. To screen out key genes and clinicopathologic factors related to the prognosis of MPM patients.Methods:The second generation sequencing data, somatic mutation data and clinical pathological data of 86 MPM cases and gene chip expression data of 89 MPM cases were downloaded from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) in March 2020. Summarize the gene mutation profile of tissue samples in the TCGA database and analyze the relationship between the expression level of high-frequency mutation genes and the clinicopathological characteristics, asbestos exposure history and prognosis of MPM patients. The genes significantly related to MPM prognosis were screened out for gene set enrichment analysis (GSEA) . Survival analysis and GSEA were performed for the selected key genes and clinicopathological features verification using the microarray expression data from the GEO database.Results:The top 10 genes with highest single nucleotide variations frequencies were BAP1, NF2, TP53, TTN, SETD2, LATS2, CCDC168, FAT4, PTCH1 and ZNF469. The high expression rates of NF2, TP53, SETD2 and CCDC168 genes in wild type were higher than those of mutated type, and the differences were statistically significant ( P<0.05) . Cox multivariate analysis of TCGA data showed that MPM patients with epithelial type ( HR=0.425, 95% CI: 0.235-0.767, P<0.01) and SETD2 low expression ( HR=0.516, 95% CI: 0.307-0.868, P=0.011) had lower risk of death. The survival analysis of GEO data verified that patients with epithelial type MPM had longer survival time, while patients with sarcoma type MPM had shortest survival time ( P<0.01) . GSEA showed that SETD2 was involved in G2M checkpoint, E2F targets, MYC signaling pathways, protein secretion, mitotic spindle, MTORC1 pathway, TGF-β pathway, androgen response and uv response. Conclusion:MPM is accompanied with higher frequency of gene mutations represented by BAP1, NF2, TP53, TTN, SETD2, LATS2 and so on. SETD2 expression level and epithelia type of MPM may be influential factors for MPM prognosis.
		                        		
		                        		
		                        		
		                        	
8.microRNA-30d can inhibit the proliferation, migration and invasion of human mesothelial cell MSTO-211H
Xiuyuan YUAN ; Fangfang ZHANG ; Yali HUANG ; Zhenyu JIA ; Li JU ; Yun XIAO ; Hailing XIA ; Yanan GAO ; Min YU ; Man YU ; Xing ZHANG ; Lijin ZHU
Chinese Journal of Industrial Hygiene and Occupational Diseases 2021;39(2):99-104
		                        		
		                        			
		                        			Objective:To investigate the inhibitory effect and molecular mechanism of microRNA-30d (miR-30d) in the process of proliferation, migration and invasion of malignant mesothelioma cell line MSTO-211H.Methods:In April 2017, the human MSTO-211H cells was used to establish miR-30d overexpressed MSTO-211H cell model by transfection of miR-30d mimics. The qRT-PCR was performed to detect the expression level of miR-30d in the cells transfected miR-30d mimics. The effects of miR-30d on the proliferation, apoptosis, migration and invasion of MSTO-211H cells were analyzed by CCK-8 experiment, flow cytometry, cell scratch experiment and Transwell method.Results:After transfection of miR-30d, the expression level of miR-30d in the MSTO-211H+miR-30d cells group was significantly higher than MSTO-211H+miR NC cells group ( P<0.01) . The cell activity of MSTO-211H+miR-30d group (105.13%±2.35%) was significantly lower than MSTO-211H+miR NC cells group (115.40%±1.35%) , and the level of apoptosis (3.97%±0.36%) was significantly higher than MSTO-211H+miR NC cells group (1.47%±0.10%) ( P<0.01) . The relative migration areas at 12 and 24 h of MSTO-211H+miR-30d cells group (9.35±3.16 μm 2 and 58.19±1.82 μm 2) were significantly lower than MSTO-211H+miR NC cells group (54.42 ±5.26 μm 2 and 88.32 ±1.96 μm 2) ( P<0.01) . Compared with the MSTO-211H+miR NC cells group, the numbers of cell migration and cell invasion were reduced in the MSTO-211H+miR-30d cells group ( P<0.01) . Conclusion:miR-30d can regulate the progression of malignant pleural mesothelioma by inhibiting the proliferation, apoptosis, migration and invasion of MSTO-211H cells.
		                        		
		                        		
		                        		
		                        	
9.Study on malignant transformation of MeT-5A cells induced by chrysotile
Fangfang ZHANG ; Xiuyuan YUAN ; Yanan GAO ; Min ZHANG ; Min YU ; Man YU ; Yun XIAO ; Li JU ; Yali HUANG ; Xing ZHANG ; Lijin ZHU
Chinese Journal of Industrial Hygiene and Occupational Diseases 2021;39(2):105-109
		                        		
		                        			
		                        			Objective:To study the cytotoxicity and malignant transformation ability of chrysotile on MeT-5A cells.Methods:In June 2016, lactate dehydrogenase (LDH) method was used to detect the cytotoxicity of chrysotile to MeT-5A cells. MeT-5A cells were treated with 5 μg/cm 2 chrysotile intermittently for 24 h a time, once a week and a total of 28 times. After the cells showed anchorage independent growth, the cell features of malignant transformation were identified by colony forming frequency in soft agar, and the soft agar colony formation rates were calculated. The activities of key speed limiting enzymes of glycolysis metabolism including hexokinase (HK) , phosphofructokinase (PFK) and pyruvate kinase (PK) were determined by UV colorimetry. Results:Chrysotile was cytotoxic to MeT-5A cells in a concentration-dependent decline. Compared with the control group, the relative survival rates of MeT-5A cells were significantly decreased after exposed to chrysotile at 10, 20, 40 and 80 μg/cm 2 ( P<0.05) . After 28 times of exposure, the growth rate of the cells in chrysotile transformed MeT-5A cells was accelerated, the arrangement was disordered, the contact inhibition was lost, and the double layer growth appeared, which could grow on soft agar. The colony forming rate of the chrysotile transformed MeT-5A cells was 18.33‰±2.49‰. Compared with the control group (0) , the difference was statistically significant ( P<0.01) . The activities of glycolysis related kinase including PK [ (19.51±1.52) U/L], PFK[ (0.12±0.02) U/10 4 cell] and HK[ (0.26±0.01) U/10 4 cell] were increased in the chrysotile transformed MeT-5A cells compared with control group [ (25.00±1.04) U/L、(0.15±0.01) U/10 4 cell and (0.33±0.01) U/10 4 cell] ( P<0.01) . Conclusion:Chrysotile can induce malignant transformation of MeT-5A cells and increase the activities of glycolysis related kinases including PK, PFK and HK.
		                        		
		                        		
		                        		
		                        	
10.The impact of CD8 and CTLA-4 expression on histopathological character and survival in mesothelioma
Min YU ; Man YU ; Shibo YING ; Xiuyuan YUAN ; Zhaoqiang JIANG ; Jianlin LOU ; Lijin ZHU ; Xing ZHANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2021;39(2):85-90
		                        		
		                        			
		                        			Objective:To investigate the survival and death risk factors of mesothelioma cases stratified by the expression levels of CD8 and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) , providing new clue to evaluate disease progression and clinical outcome.Methods:This was a retrospective case report, which included 47 clinically and pathologically confirmed mesothelioma cases on November 2016. Their clinical and pathological information, asbestos exposure history and survival data were collected. Infiltrated lymphocyte, 5-methylcytosine (5-mC) , CTLA-4, CD8 and Ki-67 antigen were detected using hematoxylin-eosin staining and immunohistochemistry. Survival time and death risk factors of mesothelioma patients with different CD8 and CTLA-4 protein expression characteristics were analyzed. And analyze the influence of Ki-67 expression on the survival of patients with different CD8 and CTLA-4 protein and gene expression characteristics.Results:Among the 47 cases, 63.8% (30/47) had low/medium level of infiltrated lymphocyte. The immunohistochemistry scores of CTLA-4, CD8, 5-mC and Ki-67 were 92.97 (54.95, 120.65) , 72.41 (36.62, 89.82) , 11.09 (3.40, 52.89) and 5.88 (2.41, 11.48) , respectively. Patients with CD8 high CTLA-4 high had higher 5-mC level than those with CD8 high CTLA-4 low ( P<0.01) . The median survival time of 27 cases was 0.83±0.29 year. The median survival times of those with CD8 high CTLA-4 high and CD8 high CTLA-4 low were 0.58±0.51 year and 0.83±0.30 year, respectively ( P=0.521) . The immunohistochemistry score of Ki-67 ≥5.88 was an independent death risk factor for patients with CD8 high CTLA-4 low ( HR=8.40, P=0.01) . Under different CD8 and CTLA-4 protein expression characteristics, in the patients with CD8 high CTLA-4 low, the median survival times of those with high and low Ki-67 expression were 0.57±0.11 years and 2.31±0.46 years, respectively ( P<0.01) . Under different CD8 and CTLA-4 mRNA expression characteristics, in the patients with CD8 high CTLA-4 low, the median survival times of those with high and low Ki-67 mRNA expression were 1.20±0.36 years and 3.38±0.43 years, respectively ( P=0.018) . Conclusion:Mesothelioma case with high CD8 but low CTLA-4 content might coexist DNA hypomethylation. In the presence of high Ki-67 expression, their survival time appears to be shortened with increased death risk.
		                        		
		                        		
		                        		
		                        	
            

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