1.The prognostic value of BAP1 protein loss in patients with malignant mesothelioma
Yiqiu CHEN ; Zhibin GAO ; Wei SHEN ; Shibo YING ; Xianglei HE ; Xing ZHANG ; Zhaoqiang JIANG ; Jianlin LOU
Chinese Journal of Industrial Hygiene and Occupational Diseases 2024;42(11):815-820
Objective:To explore the prognostic value of BRCA1-associated protein 1 (BAP1) expression loss in patients with malignant mesothelioma (MM) .Methods:A total of 82 MM patients from January 1998 to December 2017 in Zhejiang Province were selected to detect the expression of BAP1 protein by immunohistochemical analysis. Kaplan-Meier method was used to draw the survival curve, and multivariate Cox proportional risk model was used to analyze the factors affecting the survival rate.Results:Among 82 MM patients, 61 (74.4%) were female, aged (57±11) years. BAP1 protein expression was deficient in 39 patients (47.6%). The survival rate was correlated with the loss of BAP1 protein expression and age (χ 2=5.27, 5.66, P=0.022, 0.017). Subgroup analysis showed that loss of BAP1 protein expression was associated with better prognosis in MM patients <57 years of age, female, pleural MM, epithelial MM, and treated with drugs or surgery ( P<0.05). Multivariate model results showed that positive expression of BAP1 protein ( HR=3.75, 95% CI: 2.23-6.30, P<0.001) and age ≥57 years ( HR=1.66, 95% CI: 1.01-2.72, P=0.049) were risk factors for survival in patients with MM. Conclusion:Loss of BAP1 protein expression may be an independent prognostic factor in patients with MM, which is associated with longer survival.
2.The prognostic value of BAP1 protein loss in patients with malignant mesothelioma
Yiqiu CHEN ; Zhibin GAO ; Wei SHEN ; Shibo YING ; Xianglei HE ; Xing ZHANG ; Zhaoqiang JIANG ; Jianlin LOU
Chinese Journal of Industrial Hygiene and Occupational Diseases 2024;42(11):815-820
Objective:To explore the prognostic value of BRCA1-associated protein 1 (BAP1) expression loss in patients with malignant mesothelioma (MM) .Methods:A total of 82 MM patients from January 1998 to December 2017 in Zhejiang Province were selected to detect the expression of BAP1 protein by immunohistochemical analysis. Kaplan-Meier method was used to draw the survival curve, and multivariate Cox proportional risk model was used to analyze the factors affecting the survival rate.Results:Among 82 MM patients, 61 (74.4%) were female, aged (57±11) years. BAP1 protein expression was deficient in 39 patients (47.6%). The survival rate was correlated with the loss of BAP1 protein expression and age (χ 2=5.27, 5.66, P=0.022, 0.017). Subgroup analysis showed that loss of BAP1 protein expression was associated with better prognosis in MM patients <57 years of age, female, pleural MM, epithelial MM, and treated with drugs or surgery ( P<0.05). Multivariate model results showed that positive expression of BAP1 protein ( HR=3.75, 95% CI: 2.23-6.30, P<0.001) and age ≥57 years ( HR=1.66, 95% CI: 1.01-2.72, P=0.049) were risk factors for survival in patients with MM. Conclusion:Loss of BAP1 protein expression may be an independent prognostic factor in patients with MM, which is associated with longer survival.
3.The value of lncRNA JPX in diagnosis and prognosis of mesothelioma
Mingying JIN ; Wei SHEN ; Junfei CHEN ; Lingfang FENG ; Shibo YING ; Hailing XIA ; Junqiang CHEN ; Yiqiu CHEN ; Zhaoqiang JIANG ; Jianlin LOU
Journal of Preventive Medicine 2023;35(3):235-238
Objective :
To examine the diagnostic and prognostic value of long non-coding RNA (lncRNA) JPX in mesothelioma, so as to provide insights into diagnosis and prognosis of mesothelioma.
Methods:
Patients with clinically definitive diagnosis of mesothelioma from 2015 to 2019 that were sampled from asbestos processing plants in Zhejiang Province from 2015 to 2019 were recruited in the mesothelioma group, while healthy residents without asbestos exposure or asbestos-related diseases in the same area served as controls. Participants' demographics, pathologic diagnosis and imaging features were collected, and the expression of blood lncRNA JPX was detected using lncRNA microarrays. The diagnostic value of lncRNA JPX for mesothelioma was evaluated using the receiver operating characteristic (ROC) curve, and the correlation between lncRNA JPX expression and prognosis was examined among mesothelioma patients using survival analysis.
Results:
There were 17 subjects in the mesothelioma group, with a mean age of (65.71±8.36) years, and 34 subjects in the controls, with a mean age of (64.24±8.70) years. LncRNA microarray detected significantly high lncRNA JPX expression in mesothelioma patients, and higher blood lncRNA JPX expression was detected in the mesothelioma group than in the control group [median (interquartile range), 1.10 (1.31) vs. 0.89 (0.54); t'=-2.300, P=0.034]. The area under the ROC curve was 0.673 (95%CI: 0.507-0.839, P=0.046), and if the cutoff was 1.759, the sensitivity and specificity were 35.3% and 100.0%, respectively. Survival analysis showed no significant difference in the survival rate of mesothelioma patients between the high lncRNA JPX expression group and the low expression group (χ2=0.212, P=0.645).
Conclusions
LncRNA JPX overexpression is detected in the blood of patients with mesothelioma, and lncRNA JPX expression presents a diagnostic value for mesothelioma; however, it shows little prognostic value for mesothelioma.
4.Objective evaluation of the effect of posterior scleral reinforcement surgery on the prevention and control of high myopia
Chinese Journal of Ocular Fundus Diseases 2023;39(8):626-633
Due to the high incidence and the earlier onset age, high myopia has become an important public health problem in China. Posterior scleral reinforcement surgery has been developed for over 60 years in order to control the rapid progression and complications of high myopia. By suturing a certain size of material on the surface of the posterior eyeball, thickness and elasticity modulus of the local sclera significantly increase. As the result, the rapid growth of the axial length and the chorioretinopathy could be alleviated. At present, controversies about its clinical efficacy and safety still exist, so posterior scleral reinforcement surgery has not been widely carried out all over the world. An in-depth analysis of the mechanism, surgical manipulations and materials, the clinical application status of posterior scleral reinforcement surgery on control of high myopia can provide a basis for further standardized application of this surgery
5.Recent advances in developing small-molecule inhibitors against SARS-CoV-2.
Rong XIANG ; Zhengsen YU ; Yang WANG ; Lili WANG ; Shanshan HUO ; Yanbai LI ; Ruiying LIANG ; Qinghong HAO ; Tianlei YING ; Yaning GAO ; Fei YU ; Shibo JIANG
Acta Pharmaceutica Sinica B 2022;12(4):1591-1623
The COVID-19 pandemic caused by the novel SARS-CoV-2 virus has caused havoc across the entire world. Even though several COVID-19 vaccines are currently in distribution worldwide, with others in the pipeline, treatment modalities lag behind. Accordingly, researchers have been working hard to understand the nature of the virus, its mutant strains, and the pathogenesis of the disease in order to uncover possible drug targets and effective therapeutic agents. As the research continues, we now know the genome structure, epidemiological and clinical features, and pathogenic mechanism of SARS-CoV-2. Here, we summarized the potential therapeutic targets involved in the life cycle of the virus. On the basis of these targets, small-molecule prophylactic and therapeutic agents have been or are being developed for prevention and treatment of SARS-CoV-2 infection.
6.Survival analysis of 36 patients with malignant mesothelioma
SHEN Wei ; LIU Jiaqi ; CHEN Junfei ; YING Shibo ; XIA Hailing ; FENG Lingfang ; JIN Mingying ; JIANG Zhaoqiang
Journal of Preventive Medicine 2022;34(1):66-69
Objective :
To analyze the survival of patients with malignant mesothelioma, so as to provide insights into the management of malignant mesothelioma.
Methods :
Totally 36 patients with malignant mesothelioma admitted to Cixi Third People’s Hospital from October 2012 to January 2021 were enrolled, and the demographic features, exposure to asbestos, and diagnosis and treatment were retrospectively reviewed. The survival rate and median survival time were calculated with the life-table method, and the factors affecting the survival rate of malignant mesothelioma were identified using the Kaplan-Meier estimate and log-rank test.
Results :
The 36 patients with malignant mesothelioma included 6 men ( 16.67% ) and 30 women ( 83.33% ), and had a median age of 61 ( interquartile range, 14 ) years. There were 30 cases with pleural malignant mesothelioma ( 83.33% ) and 6 cases with peritoneal malignant mesothelioma ( 16.67% ), 32 cases ( 88.89% ) with a history of occupational exposure to asbestos, and 26 cases ( 72.22% ) receiving palliative treatment. The 1-, 2- and 3-year cumulative survival rates were 30%, 15% and 3%, respectively, and the median survival time was 0.71 years. In addition, there were no significant differences in the survival period among patients with malignant mesothelioma in terms of gender, age, route of asbestos exposure, duration of asbestos exposure, pathogenic site and treatment regimens ( P>0.05 ).
Conclusion
The 36 patients with malignant mesothelioma had a median survival period of 0.71 years, and no association was found between the survival period and asbestos exposure or pathogenic site.
7.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.
8.Advances in the cytotoxic mechanism of nanomaterials graphene oxide
Chinese Journal of Industrial Hygiene and Occupational Diseases 2021;39(3):237-240
Graphene oxide is a novel two-dimensional carbon nanomaterial, but it has potential risks for the health of occupationally exposed workers. This article briefly reviews the research progress on the cytotoxic mechanism of graphene oxide and its derivatives in terms of oxidative stress, physical damage and dysfunction of enzyme activity. This review also discusses effective measures for the mitigation of cytotoxicity in order to provide helpful evidence for occupational health risk and biological safety assessment of graphene nanomaterials in China.
9.Effect of PPAR-γ agonist pioglitazone on the prolifeiration of malignant nesothelionma cells induced by HMGB1
Yanbin WANG ; Wei SHEN ; Yihan GAN ; Jin ZOU ; Yu ZHANG ; Lijin ZHU ; Li JU ; Zhaoqiang JIANG ; Shibo YING
Chinese Journal of Industrial Hygiene and Occupational Diseases 2021;39(9):641-647
Objective:To investigate the effect and mechanism of PPAR-γ agonist Pioglitazone (PGZ) on the proliferation of malignant mesothelioma (MM) cells.Methods:In December 2019, MM cell lines MSTO-211H and NCI-H2452 were incubated with different final concentrations of PGZ (0, 10, 50, 100, 150, and 200 μmol/L) for different periods of time (24 h, 48 h, and 72 h) , and then the cell proliferation level was detected by CCK8 assay. After given various final concentration of PGZ (0, 10, 50, 100, 150, 200 μmol/L) the for 72 hours, the changes of number and morphology of MM cells were observed under an inverted microscope. The expressions of PPAR-γ and HMGB1 mRNA were determined by real-time fluorescence quantitative reverse transcription-polymerase chain reaction (qRT-PCR) after treatment of MM cells with PGZ of 0, 10, 50, 100 μmol/L for 72 h. The MM cells were treated with PGZ at concentration of 0, 100 μmol/L for 72 h, and the protein expressions of HMGB1 were examined using Western blotting and immunofluorescence; the protein expressions of Ki67 were assessed by immunohistochemistry.Results:The cell viability rate of MM cells was decreased after treated with PGZ ( P<0.05) . Cell number in PGZ-treated group was significantly less than that in control group and morphology changes were observed under light microscope. QRT-PCR results revealed significantly increased PPAR-γ mRNA expression in the PGZ-treated group compared to the control group ( P<0.05) . There was a significant decrease in the mRNA expression level of HMGB1 in the PGZ-treated group (100 μmol/L) as compared to the control group in MSTO-211H ( P<0.05) ; however, the expression level of HMGB1 in NCI-H2452 was an increase or no significant differences ( P>0.05) . Western blotting and immunofluorescence results showed that the protein expression of HMGB1 was reduced in the PGZ-treated group compared with the control group in MSTO-211H ( P<0.05) , but the protein expression of that in NCI-H2452 was no significant differences ( P>0.05) . Immunohistochemistry results showed increased expression of proliferation marker Ki-67. Conclusion:Pioglitazone suppresses the proliferation of MM cells through inhibition of HMGB1 by the activation of PPAR-γ.
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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