1.Effect of spindle checkpoint on Akt2-mediated paclitaxel-resistance in A2780 ovarian cancer cells.
Ting, ZHOU ; Yindi, BAO ; Shuangmei, YE ; Danhui, WENG ; Gang, CHEN ; Yunping, LU ; Ding, MA ; Shixuan, WANG
Journal of Huazhong University of Science and Technology (Medical Sciences) 2010;30(2):206-11
Recent evidence has suggested that Akt2 plays an important role in the protection of cells from paclitaxel (PTX)-induced apoptosis and control of the cell cycle. In addition, some scholars suggested that the PTX sensitivity depends on a functional spindle assembly checkpoint. In the present study, we investigated the role of the Akt2/Bub1 cross-talking in apoptosis and cell cycle after exposure of the A2780 ovarian cancer cells to paclitaxel (PTX). Recombinant expression plasmid WT-Akt2 was transfected into A2780 cells by lipofectamine2000, and then the expression level of Akt2 gene was detected by using RT-PCR and Western blotting. Cell apoptosis and cell cycle were detected by flow cytometry and Hoechst 33342 staining after treatment with PTX. Moreover, we compared the expression level of Bub1 in different groups by Western blotting. Our study showed that up-regulation of Akt2 contributed to A2780 ovarian cancer cells overriding PTX-induced G(2)/M arrest, and inhibited Bub1 expression. Our findings might shed light on the molecular mechanism of PTX-induced resistance in ovarian cancer and help develop novel anti-neoplastic strategies.
2.Mitochondrial ultrastructure and function changes in SH?SY5Y induced by manganese
Dongmei SONG ; Li CHEN ; Junxiang MA ; Yuanyuan ZHANG ; Shixuan ZHANG ; Caixia GUO ; Tian CHEN ; Lin TIAN ; Piye NIU
The Journal of Practical Medicine 2017;33(5):680-683
Objective To explore the mechanism of SH?SY5Y mitochondrial dysfunction treated by manganese to find a new potential therapeutic target. Methods Transmission Electron Microscopy(TEM)to observe the morphology of mitochondria. Cell treated with 250μmol/L for periods of time(2 h, 4 h, 6 h)while mitochondrial membrane potential(MMP)and ROS can be detected by FCM and fluorescence microplate reader. Results After treating with MnCl2 in 6 h, TEM images showed early vacuoles, lamellar structures of SH?SY5Y cells. Then test the mitochondrial membrane potential and showed that MMP would be decreased gradually. Meanwhile, analysis showed that in comparison with control, treatment group had a higher ROS level respectively (P < 0.05). Conclusion MnCl2 can cause mitochondrial damage through a mechanism closely related to disrupt the MMP or generate abundant ROS.
3.Analysis on the laboratory examination characteristics in 22 patients with acute megakaryoblastic leukemia.
Shuxu DONG ; Shixuan ZHAO ; Ying WANG ; Wen CUI ; Chengwen LI ; Yumei CHEN ; Xiaofan ZHU ; Yingchang MI ; Yongxin RU ; Jianxiang WANG
Chinese Journal of Hematology 2016;37(4):297-301
OBJECTIVETo analyze the ultra microstructures and the expression of platelet peroxidase (PPO) of megakaryocytes from bone marrow, their clinical manifestations and laboratory characteristics in patients with acute megakaryoblastic leukemia (AMKL).
METHODSKaryocytes from bone marrow of 22 AMKL patients were divided into two parts by lymphocyte separation liquid, one part was used to prepare the ordinary transmission electron microscope specimens to observe the morphological structures of megakaryocytes, the other was used to prepare the histochemical specimens of platelet peroxidase to analyze the positive reaction of PPO in AMKL, which were coupled with the patients' data of with bone marrow morphology, cell chemistry, and chromosome karyotype examination.
RESULTSMegakaryocytes from 17 of 22 patients were in the first stage, less than 20 µm in diameter, the nucleis were round, the cytoplasm contained microtubules, membranous vesicles and minute dense granules, no demarcation membrane system and surface-connected canalicular system, less dense granules and α-granules; Megakaryocytes in 5 cases were mainly in the first stage, while containing second and third stage megakaryocytes; the positive rate of PPO in megakaryocytes of 22 patients was 0-80%. The primitive and naive megakaryocytes were found in bone marrow smears of 22 cases, CD41 staining of the megakaryocytes was detected in the primitive and naive megakaryocytes, and more complex chromosome karyotype anomalies were observed.
CONCLUSIONThe majority of megakaryocytes in AMKL patients were the first stage ones, the rest were second and third stage ones, and the positive PPO reaction was significantly different. CD41 staining of the megakaryocytes was specific with complex chromosome karyotypeswere.
Blood Platelets ; enzymology ; Bone Marrow ; pathology ; Cell Count ; Chromosome Aberrations ; Chromosome Disorders ; Humans ; Karyotyping ; Leukemia, Megakaryoblastic, Acute ; diagnosis ; pathology ; Megakaryocytes ; pathology ; Peroxidase ; metabolism ; Staining and Labeling
4.Effect of Spindle Checkpoint on Akt2-mediated Paclitaxel-resistance in A2780 Ovarian Cancer Cells
ZHOU TING ; BAO YINDI ; YE SHUANGMEI ; WENG DANHUI ; CHEN GANG ; LU YUNPING ; MA DING ; WANG SHIXUAN
Journal of Huazhong University of Science and Technology (Medical Sciences) 2010;30(2):206-211
Recent evidence has suggested that Akt2 plays an important role in the protection of cells from paclitaxel(PTX)-induced apoptosis and control of the cell cycle.In addition,some scholars suggested that the PTX sensitivity depends on a functional spindle assembly checkpoint.In the present study,we investigated the role of the Akt2/Bub1 cross-talking in apoptosis and cell cycle after exposure of the A2780 ovarian cancer cells to paclitaxel(PTX).Recombinant expression plasmid WT-Akt2 was transfected into A2780 cells by lipofectamine2000,and then the expression level of Akt2 gene was detected by using RT-PCR and Western blotting.Cell apoptosis and cell cycle were detected by flow cytometry and Hoechst 33342 staining after treatment with PTX.Moreover,we compared the expression level of Bubl in different groups by Western blotting.Our study showed that up-regulation of Akt2 contributed to A2780 ovarian cancer cells overriding PTX-induced G2/M arrest,and inhibited Bub1 expression.Our findings might shed light on the molecular mechanism of PTX-induced resistance in ovarian cancer and help develop novel anti-neoplastic strategies.
5.A low-dose CT reconstruction algorithm across different scanners based on federated feature learning
Shixuan CHEN ; Dong ZENG ; Zhaoying BIAN ; Jianhua MA
Journal of Southern Medical University 2024;44(2):333-343
Objective To propose a low-dose CT reconstruction algorithm across different scanners based on federated feature learning(FedCT)to improve the generalization of deep learning models for multiple CT scanners and protect data privacy.Methods In the proposed FedCT framework,each client is assigned an inverse Radon transform-based reconstruction model to serve as a local network model that participates in federated learning.A projection-domain specific learning strategy is adopted to preserve the geometry specificity in the local projection domain.Federated feature learning is introduced in the model,which utilizes conditional parameters to mark the local data and feed the conditional parameters into the network for encoding to enhance the generalization of the model in the image domain.Results In the cross-client,multi-scanner,and multi-protocol low-dose CT reconstruction experiments,FedCT achieved the highest PSNR(+2.8048,+2.7301,and +2.7263 compared to the second best federated learning method),the highest SSIM(+0.0009,+0.0165,and +0.0131 in the same comparison),and the lowest RMSE(-0.6687,-1.5956,and-0.9962).In the ablation experiment,compared with the general federated learning strategy,the model with projection-specific learning strategy showed an average improvement by 1.18 on Q1 of the PSNR and an average decrease by 1.36 on Q3 of the RMSE on the test set.The introduction of federated feature learning in FedCT further improved the Q1 of the PSNR on the test set by 3.56 and reduced the Q3 of the RMSE by 1.80.Conclusion FedCT provides an effective solution for collaborative construction of CT reconstruction models,which can enhance model generalization and further improve the reconstruction performance on global data while protecting data privacy.
6.A low-dose CT reconstruction algorithm across different scanners based on federated feature learning
Shixuan CHEN ; Dong ZENG ; Zhaoying BIAN ; Jianhua MA
Journal of Southern Medical University 2024;44(2):333-343
Objective To propose a low-dose CT reconstruction algorithm across different scanners based on federated feature learning(FedCT)to improve the generalization of deep learning models for multiple CT scanners and protect data privacy.Methods In the proposed FedCT framework,each client is assigned an inverse Radon transform-based reconstruction model to serve as a local network model that participates in federated learning.A projection-domain specific learning strategy is adopted to preserve the geometry specificity in the local projection domain.Federated feature learning is introduced in the model,which utilizes conditional parameters to mark the local data and feed the conditional parameters into the network for encoding to enhance the generalization of the model in the image domain.Results In the cross-client,multi-scanner,and multi-protocol low-dose CT reconstruction experiments,FedCT achieved the highest PSNR(+2.8048,+2.7301,and +2.7263 compared to the second best federated learning method),the highest SSIM(+0.0009,+0.0165,and +0.0131 in the same comparison),and the lowest RMSE(-0.6687,-1.5956,and-0.9962).In the ablation experiment,compared with the general federated learning strategy,the model with projection-specific learning strategy showed an average improvement by 1.18 on Q1 of the PSNR and an average decrease by 1.36 on Q3 of the RMSE on the test set.The introduction of federated feature learning in FedCT further improved the Q1 of the PSNR on the test set by 3.56 and reduced the Q3 of the RMSE by 1.80.Conclusion FedCT provides an effective solution for collaborative construction of CT reconstruction models,which can enhance model generalization and further improve the reconstruction performance on global data while protecting data privacy.
7.Primary Screening for Breast Diseases among 17618 Women in Wufeng Area, a Region with High Incidence of Cervical Cancer in China
ZHANG QINGHUA ; LIU DAN ; HANG CHUANYING ; HU TING ; SHEN JIAN ; HU MEILING ; YANG RU ; CHEN ZHILAN ; LAI ZHUHUI ; LIU GUILING ; MEI YEDONG ; XIANG QUNYING ; LI XIONG ; HUANG KECHENG ; WANG SHAOSHUAI ; PAN XIUYU ; YAN YUTING ; LI YE ; CHEN QIAN ; XI LIN ; DENG DONGRUI ; WANG HUI ; WANG SHIXUAN ; LU YUNPING ; MA DING ; LI SHUANG
Journal of Huazhong University of Science and Technology (Medical Sciences) 2012;32(2):252-256
In this study,the current status for breast diseases in a region with high-incidence of cervical cancer were epidemiologically investigated.From March to August,2009,17618 women,from Wufeng area of Hubei province,China,were recruited to screen breast diseases by using breast infrared diagnostic apparatus.Other diagnostic methods,such as B-mode ultrasound,X-ray mammography,needle biopsy and pathological examination were,if necessary,used to further confirm the diagnosis.The screening showed that 5990 of 17618 cases (34.00%) had breast diseases,5843 (33.16%) had mammary gland hyperplasia,48 (0.27%) had breast fibroadenoma,ll (0.06%) had breast carcinoma,and 88 (0.50%) had other breast diseases.The peak morbidity of breast cancer was found in the women aged 50-0 ages.The morbidity of breast cancer was significantly increased in women elder than or equal to 50 years old (n=8,0.157%) in comparison with that in the subjects younger than 50 years old (n=3,0.024%) (u=2.327,P<0.05).It was shown that the occurrence of breast diseases was concentrated in women aged 20-40 years,while the total morbidity reached its peak at the age of 30 years and then decreased sharply after age of 40.Compared with the patients elder than or equal to 40 years old (n=3289,27.46%),the morbidity rate of breast diseases was significantly increased in women less than 40 years old (2648 cases,47.18%; P<0.001).However,there was no significant difference in the morbidity of breast diseases between the age group of 20-29 years and that of 30-39 years (P=0.453),and both of them were high.There was no significant association between the morbidity of breast diseases and cervical cancer.Since the morbidity of breast diseases was higher among young women,more attention should be paid to the screening of breast diseases among young women for early diagnosis.
8.Long-term effect of environmental cadmium exposure on human body's mineral metabolic balance
Haituan LING ; Rui HUANG ; Xuxia LIANG ; Zhixue LI ; Jing WANG ; Jianbin TAN ; Shixuan WU ; Ping WANG ; Zihui CHEN ; Qiong HUANG ; Yingjian LYU ; Qi JIANG ; Xingfen YANG ; Yongning WU
Chinese Journal of Preventive Medicine 2016;50(4):316-321
Objective To investigate the effect of long?term exposure to environmental cadmium on eight mineral element's metabolic balance of human body. Methods To choose a high cadmium area polluted by smelting and mining north of Guangdong province and a cadmium?free area with a similar economic level, and living and eating habit of residents as a contrast from April 2011 to August 2012. Stratified random sampling and clustered sampling method were adopted to choose the non?occupationally cadmium?exposed respondents who have lived in local area for more than 15 years, older than 40 years, having local rice and vegetable as the main dietary source, with simple and relatively stable diet, and without diabetes, kidney disease, thyroid disease, liver disease or other history of chronic disease. This study included 298 respondents, of whom 155 were in cadmium exposure group and 143 in control group. Questionnaires was used to acquire their health status and their morning urine samples were collected. Electrolytically coupled plasma mass spectrometry (ICP?MS) was used to test the concentrations of sodium (Na), magnesium (Mg), phosphorus (P), potassium (K), calcium (Ca), copper (Cu), zinc (Zn) and iodine (I). The Mann?Whitney U test method was used to compare the differences of concentrations of urinary cadmium, Na, Mg, P, K, Ca, Cu, Zn, I, and the ratio of Na to K (Na/K), Ca to P (Ca/P) between exposed group and control group.χ2 test was used to compare the abnormal rate of urinary cadmium between exposed group and control group. Pearson correlation and multiple regression method were used to investigate the relationship between urinary cadmium levels, gender, age, smoking, passive smoking, and minerals. Results The urinary cadmium level P50 (P25-P75) in exposed group was 5.45 (2.62-10.68)μg/g·cr, which was higher than that of the control group, which was 1.69 (1.22-2.36)μg/g · cr (Z=-10.49, P<0.001). The abnormal rate of urinary cadmium was 51.6%(80/155), which was higher than that of the control group (2.8%(4/143)) (χ2=87.56,P<0.001). The urinary Ca, Cu, Zn, and I level P50 (P25-P75) of exposed group were 173.80 (114.40-251.70), 20.55 (14.95-28.44), 520.23 (390.25-647.15), and 246.94 (203.65-342.97)μg/g · cr, which were higher than those in control group (142.42 (96.87-179.11), 15.44 (12.26-20.98), 430.09 (309.85-568.78) and 213.85 (156.70-281.63) μg/g · cr, respectively) (Z values were-4.33,-5.04,-3.47 and-4.24, all P values<0.001). The urinary P, K level P50 (P25-P75) of exposed group were 582.50 (463.20-742.8), 890.10 (666.00-1 305.40) μg/g · cr, which were lower than control group (694.50 (546.20-851.17), 1 098.58 (904.53-1 479.18) μg/g · cr) (Z values were-3.36,-4.02, all P values <0.001). on Based the results of Pearson correlation analysis, urinary cadmium was positively correlated with urinary Ca, Cu, Zn, and I, and the correlation coefficients were 0.31, 0.61, 0.38, and 0.25, respectively(all P values<0.05). Based on the results of multiple regression analysis, urinary cadmium levels contributed most to the metabolic balance of urinary Ca, Cu, Zn and I. The standardized regression coefficients were 0.31, 0.59, 0.39, and 0.24, respectively (all P values<0.001). Conclusion Long?term environmental exposure to cadmium affected the metabolic balance of Ca, Cu, Zn and I in human body.
9.Cadmium burden and renal dysfunction among residents in cadmium-polluted areas:A 3-year ;follow-up study
Zhixue LI ; Ping WANG ; Rui HUANG ; Xuxia LIANG ; Zhongjun DUN ; Qi JIANG ; Qiong HUANG ; Haituan LING ; Jing WANG ; Jianbin TAN ; Shixuan WU ; Zihui CHEN ; Yanhong GAO ; Yingjian LYU ; Yongning WU ; Xingfen YANG
Chinese Journal of Preventive Medicine 2016;50(4):322-327
Objective To investigate dynamic change of cadmium body burden and renal dysfunction among residents living in cadmium?polluted areas. Methods From April to July of 2011, the cadmium?polluted areas of northern Guangdong province in China was chosen as the study site. Based on the levels of cadmium pollution in soil and rice, the survey areas were divided into low exposed group (average concentration of cadmium was 0.15-0.40 mg/kg, 0.5-1.0 mg/kg in rice and soil, respectively) and high exposed group (average concentration of cadmium was >0.40 mg/kg, >1.0 mg/kg in rice and soil, respectively). Stratified random sampling and cluster sampling method of epidemiological investigations were carried out among 414 local residents who lived in cadmium exposure areas for more than 15 years, aged above 40, and without occupational cadmium exposure, including 168 and 246 residents in low and high exposed group, respectively. From March to June of 2014, 305 respondents of those who participated in 2011 were successfully traced, including 116 and 189 respondents in low and high exposed group, respectively. We used health questionnaires to acquire their health status. Home?harvested rice and vegetable samples were collected using quartering method for detection of cadmium level, including 190 rice samples, 161 vegetable samples in 2011 and 190 rice samples, 153 vegetable samples in 2014. Urine specimens of residents were collected for the detection of urinary cadmium and creatinine as well as renal dysfunction biomarkers, namely, N?acetyl?beta?D?glucosamidase (NAG) andβ2?microglobulin (β2?MG), respectively. In 2011 and 2014, Chi?square test was used to investigate the differences of abnormality of cadmium concentration in rice, vegetables and urinary cadmium,β2?MG,and NAG that were expressed as odds ratio (OR) and 95%confidence intervals (95%CI). Results In 2011 and 2014, cadmium concentration P50 (P25-P75) in rice was 0.43 (0.17-1.10) mg/kg,and 0.42 (0.20-1.14) mg/kg, respectively (Z=-0.77, P=0.440). In 2011 and 2014, cadmium concentrations P50 (P25-P75) in vegetables were 0.13 (0.07-0.34) mg/kg,and 0.25 (0.12-0.59) mg/kg, respectively, with abnormal rates of 38.5%(62/161) and 60.8%(93/153), respectively. In 2014, both average concentration and abnormal rate of cadmium in vegetables were higher than those in 2011 (Z=-4.69,P<0.001 andχ2=15.58, P<0.001). Concentrations of urinary cadmium P50 (P25-P75) in high exposed group were 7.90 (3.96-14.91)μg/g creatinine, 8.64 (4.56-17.60)μg/g creatinine in 2011 and 2014, respectively. Contrary to that in 2011, urinary cadmium of high exposed group was significantly increased in 2014 (Z=-2.80 ,P=0.005). In 2011 and 2014, concentrations of β2?MG, NAG P50 (P25-P75) were 0.15 (0.07-0.29)μg/g creatinine, 0.15 (0.07-0.45)μg/g creatinine,and 7.12 (5.05-10.65) U/g creatinine, 13.55 (9.1-19.84) U/g creatinine, respectively, with abnormal rates of 7.5% (23/305), 15.1% (46/305) ,8.2%(25/305) , and 33.8% (103/305), respectively. Compared with baseline in 2011, average concentrations ofβ2?MG, NAG significantly increased in 2014 (Z=-2.263,P=0.024 and Z=-12.52,P<0.001), and abnormal rates ofβ2?MG, NAG were also higher in 2014 (χ2=15.61,P<0.001 andχ2=64.72,P<0.001), with odds ratio (OR) of 2.00 (95%CI:1.23-3.24) and 4.12 (95%CI:2.87-5.92). Conclusion Environmental cadmium pollution of crops such as rice and vegetables in survey areas continued to remain high. Body burden of cadmium might kept at sustainably high levels and renal dysfunction was worsened after continuous, long?term cadmium exposure. Our results suggested that NAG might be more sensitive than β2?MG to serve as an indicator for an individual's future tubular function.
10.Long-term effect of environmental cadmium exposure on human body's mineral metabolic balance
Haituan LING ; Rui HUANG ; Xuxia LIANG ; Zhixue LI ; Jing WANG ; Jianbin TAN ; Shixuan WU ; Ping WANG ; Zihui CHEN ; Qiong HUANG ; Yingjian LYU ; Qi JIANG ; Xingfen YANG ; Yongning WU
Chinese Journal of Preventive Medicine 2016;50(4):316-321
Objective To investigate the effect of long?term exposure to environmental cadmium on eight mineral element's metabolic balance of human body. Methods To choose a high cadmium area polluted by smelting and mining north of Guangdong province and a cadmium?free area with a similar economic level, and living and eating habit of residents as a contrast from April 2011 to August 2012. Stratified random sampling and clustered sampling method were adopted to choose the non?occupationally cadmium?exposed respondents who have lived in local area for more than 15 years, older than 40 years, having local rice and vegetable as the main dietary source, with simple and relatively stable diet, and without diabetes, kidney disease, thyroid disease, liver disease or other history of chronic disease. This study included 298 respondents, of whom 155 were in cadmium exposure group and 143 in control group. Questionnaires was used to acquire their health status and their morning urine samples were collected. Electrolytically coupled plasma mass spectrometry (ICP?MS) was used to test the concentrations of sodium (Na), magnesium (Mg), phosphorus (P), potassium (K), calcium (Ca), copper (Cu), zinc (Zn) and iodine (I). The Mann?Whitney U test method was used to compare the differences of concentrations of urinary cadmium, Na, Mg, P, K, Ca, Cu, Zn, I, and the ratio of Na to K (Na/K), Ca to P (Ca/P) between exposed group and control group.χ2 test was used to compare the abnormal rate of urinary cadmium between exposed group and control group. Pearson correlation and multiple regression method were used to investigate the relationship between urinary cadmium levels, gender, age, smoking, passive smoking, and minerals. Results The urinary cadmium level P50 (P25-P75) in exposed group was 5.45 (2.62-10.68)μg/g·cr, which was higher than that of the control group, which was 1.69 (1.22-2.36)μg/g · cr (Z=-10.49, P<0.001). The abnormal rate of urinary cadmium was 51.6%(80/155), which was higher than that of the control group (2.8%(4/143)) (χ2=87.56,P<0.001). The urinary Ca, Cu, Zn, and I level P50 (P25-P75) of exposed group were 173.80 (114.40-251.70), 20.55 (14.95-28.44), 520.23 (390.25-647.15), and 246.94 (203.65-342.97)μg/g · cr, which were higher than those in control group (142.42 (96.87-179.11), 15.44 (12.26-20.98), 430.09 (309.85-568.78) and 213.85 (156.70-281.63) μg/g · cr, respectively) (Z values were-4.33,-5.04,-3.47 and-4.24, all P values<0.001). The urinary P, K level P50 (P25-P75) of exposed group were 582.50 (463.20-742.8), 890.10 (666.00-1 305.40) μg/g · cr, which were lower than control group (694.50 (546.20-851.17), 1 098.58 (904.53-1 479.18) μg/g · cr) (Z values were-3.36,-4.02, all P values <0.001). on Based the results of Pearson correlation analysis, urinary cadmium was positively correlated with urinary Ca, Cu, Zn, and I, and the correlation coefficients were 0.31, 0.61, 0.38, and 0.25, respectively(all P values<0.05). Based on the results of multiple regression analysis, urinary cadmium levels contributed most to the metabolic balance of urinary Ca, Cu, Zn and I. The standardized regression coefficients were 0.31, 0.59, 0.39, and 0.24, respectively (all P values<0.001). Conclusion Long?term environmental exposure to cadmium affected the metabolic balance of Ca, Cu, Zn and I in human body.