1.Mechanisms on radiation resistance induced by an estrogen receptor in breast cancer cells
Tianpeng YANG ; Shinan ZHANG ; Huilin JI ; Linhui ZHU ; Yujie ZHANG ; Jin HUANG ; Yingren WEN ; Shumei MA ; Xiaodong LIU
Chinese Journal of Radiological Medicine and Protection 2024;44(2):88-95
Objective:To explore the effects of estrogen receptor α (ERα) encoded by protein encoding gene ESR1 on the radiation resistance of breast cancer cells and their molecular mechanisms.Methods:The ESR1 overexpression plasmid was transfected into estrogen receptor (ER)-negative breast cancer cells. Then, the shRNA-ESR1 vector was introduced into ER-positive cell to establish models with different phenotype. The ATG5 mRNA level and protein expression levels of LC3B-I, LC3B-II, P62, FIP200, ATG5, ATG7, ATG12, Beclin1, ULK1 were detected using qPCR and Western blot techniques. Cell death was measured using flow cytometry. The radiation sensitivity was determined through the colony formation assay. The mortality of breast cancer cells under the autophagy gene knockdown and overexpression or treated with estrogen receptor inhibitor (TAM) combined with ionizing radiation were detected by trypan blue staining.Results:Under the condition of 8 Gy X-ray irradiation, the knockdown of ESR1 in ER-positive ZR75 breast cancer cells promoted cell death ( t = 3.49, 3.13, P < 0.05), while the overexpression of ESR1 in ER-negative MDA-MB-231 breast cancer cells inhibited cell death ( t = 4.16, 7.48, P < 0.05). Compared to the control group, the treatment with chloroquine increased the number of formed colonies of ESR1 knockdown ZR75 cells ( t = 8.49, P < 0.05), and inhibiting autophagy could reduce the death of ZR75 cells caused by ESR1 silencing. Under the treatment with ionizing radiation, the overexpression of ESR1 in MDA-MB-231 cells promoted protective autophagy, which, however, was reduced after ESR1 knockdown in ZR75 cells. Furthermore, it was observed that the knockdown of ATG5 in ZR75 cells was associated with reduced autophagy and an increase in cell death ( t = 4.19, 6.39, P < 0.05). In contrast, the overexpression of ATG5 in ZR75 cells reversed the increase in cell death caused by ESR1 knockdown ( t = 1.70, 4.65, P < 0.05). After the treatment of ER-positive ZR75 breast cancer cells with TAM, the expressions of ATG5 and ATG12 decreased, suggesting inhibited autophagy and an increase in cell death ( t = 18.70, P < 0.05). Furthermore, these processes were promoted by ionizing radiation ( t = 16.82, P < 0.05). Conclusions:The estrogen receptor encoded by ESR1 promotes protective autophagy of ER-positive breast cancer cells by increasing ATG5, further leading to radiation resistance in ER-positive breast cancer cells. Treatment with tamoxifen combined with ionizing radiation can increase the radiation sensitivity of ER-positive breast cancer cells.
2.Predictive value of color Doppler ultrasound parameters for fetal growth restriction induced by gestational hypertension in high-altitude regions
Yongfeng ZHAO ; Guocai GAN ; Xue WANG ; Xu ZHAO ; Shumei MA ; Caiqin LI ; Cheng ZHANG
Journal of Clinical Medicine in Practice 2024;28(20):112-118
Objective To investigate the predictive value of color Doppler ultrasound parameters for fetal growth restriction (FGR) induced by hypertensive disorders of pregnancy in high-altitude regions. Methods Pregnant women with gestational hypertension who were treated between July 2020 and June 2022 at the Affiliated Hospital of Qinghai University (with altitude of 2, 300 meters, were divided into group A1 with 19 cases and group A2 with 51 cases according to occurrence of FGR), Yushu People's Hospital (with altitude of 3, 700 meters, were divided into group B1 with 25 cases and group B2 with 47 cases according to occurrence of FGR), and Civil Aviation Clinical Medical College of Peking University (plain region, control group with 71 cases) were enrolled in this study. All pregnant women in each group underwent fetal color Doppler ultrasound examination of the middle cerebral artery (MCA) and umbilical artery (UA) blood flow parameters, including pulsatility index (PI), resistance index (RI), systolic/diastolic ratio (S/D), peak systolicvelocity (PSV), and cerebroplacental ratio (CPR) at 28 weeks of gestation were detected. Multivariate Logistic regression analysis was performed to identify independent risk factors for FGR in pregnant women with gestational hypertension. Receiver operating characteristic (ROC) curves were plotted to analyze the predictive value of color Doppler parametersfor FGR. Results The UA blood flow parameters (PI, RI, S/D, PSV) of the fetuses in groups A1, A2, B1, and B2 were significantly higher than those in the control group, while the MCA blood flow parameters (PI, RI, S/D, PSV) and CPR were significantly lower (
3.Diagnostic value of ultrasound diagnosis of fetal intrauterine distress in high-risk puerperae in plateau areas
Yongfeng ZHAO ; Guocai GAN ; Xue WANG ; Xu ZHAO ; Shumei MA ; Caiqin LI ; Cheng ZHANG
Tianjin Medical Journal 2023;51(12):1374-1378
Objective To explore the diagnostic value of color Doppler ultrasound for fetal intrauterine distress(FIUD)in high-risk puerperae in plateau areas.Methods A total of 130 puerperae in plateau areas and 130 puerperae in plain areas were enrolled.According to presence or absence of FIUD in different areas,they were divided into the plateau distress group(47 cases),the plateau normal group(83 cases),the plain distress group(31 cases)and the plain normal group(99 cases).All cases underwent blood flow detection of middle cerebral artery(MCA)and umbilical artery(UA)before delivery,and cerebral-placental ratio(CPR)was calculated.The incidence of FIUD was compared between high-risk puerperae in plateau area and in plain area.Gestational age,birth weight,cesarean section rate and blood spectrum parameters of MCA and UA were compared between the four groups.The predictive value of color Doppler ultrasound parameters for FIUD was analyzed by receiver operating characteristic(ROC)curves.Results The incidence rates of FIUD and severe FIUD were higher in patients of plateau areas than those in plain areas(36.15%,13.85%vs.23.85%,4.62%,P<0.05).Compared with the plateau distress group,gestational age and birth weight were increased in the plateau normal group and the plain distress group(P<0.05).Compared with the plateau distress group,PI,RI,S/D and CPR of MCA were increased,while PI,RI and S/D of UA were decreased in the plateau normal group and the plain distress group(P<0.05).Results of ROC curve analysis showed that overall performance advantage of S/D of UA was the most obvious in the diagnosis of FIUD in high-risk puerperae in plateau areas.The diagnostic sensitivity of RI of MCA was the highest,and the diagnostic specificity of CPR was the highest(P<0.05).Conclusion Color Doppler ultrasound has good diagnostic value for FIUD in high-risk puerperae in plateau areas,which can be applied as an effective clinical screening means for FIUD.
4.Research on Employment Quality Evaluation Index System of Medical Students based on Analytic Hierarchy Process
Longting MA ; Maojie LIU ; Xueping LIANG ; Jingjing LIU ; Jingjing YU ; Peng WANG ; Xiaoli PANG ; Shumei ZHUANG
Chinese Journal of Medical Education Research 2023;22(6):956-960
Objective:To construct medical students' employment quality evaluation index system based on analytic hierarchy process (AHP), for providing basis to scientific and objective evaluation of medical students' employment quality.Methods:Two rounds of consultation with 21 experts were conducted to construct medical students' employment quality index and evaluation standard by Delphi method, and the weight of each index and evaluation standard determined by AHP. Excel 2007 and SPSS 21.0 were used to analyze the results of expert consultation. The enumeration data were expressed as frequency and percentage. The mean and coefficient of variation were used to describe the importance scores of experts on indicators at all levels. The positive coefficient, authority coefficient and coordination degree of experts were calculated, and the Kendall coordination coefficient ( W) test was carried out. Yaahp 6.0 is used to analyze the pairwise comparison matrix in the analytic hierarchy process to calculate the weight of the indicator. Results:The authority of expert consultation was ranged from 0.77 to 0.94, and the positive coefficient of experts was 100.00%. The evaluation system of medical students' employment quality was determined, which involved 3 first-class indexes, 9 second-class indexes and 35 third-class indexes, and the weight coefficients of each index were calculated by AHP.Conclusion:The evaluation index system of medical students' employment quality is reasonable, which can be used to provide reference standard for medical students' employment quality evaluation, and has certain application value.
5.Mechanism of lncRNA PRMT5-AS1 regulating radiation-induced ferroptosis in hepatocellular carcinoma cells
Tianxia YE ; Yimeng YING ; Shumei MA ; Xiaodong LIU
Chinese Journal of Radiological Medicine and Protection 2023;43(12):954-961
Objective:To evaluate the effect of long non-coding RNA PRMT5-AS1 on ferroptosis of hepatocellular carcinoma cell(HCC) after ionizing irradiation.Methods:The PRMT5-AS1 overexpression model was constructed in MHCC-97H cells and the PRMT5-AS1 knockdown model was constructed in HepG2 cells. X-ray irradiation(IR) was performed with an absorbed dose of 10 Gy and a dose rate of 3 Gy/min. Western blot and qRT-PCR were used to detect gene expression. The effect of PRMT5-AS1 expression on lipid peroxidation and ferroptosis of HCC after IR was detected by Trypan blue staining flow cytometry. The effect of PRMT5-AS1 expression on the death of HCC after IR was detected by CCK-8 assay. Dual luciferase assay to detect the binding of let-7c-5p to PRMT5-AS1 and SLC7A11.Results:Overexpression of PRMT5-AS1 in MHCC-97H cells could significantly reduce cell death induced by IR (Vector vs. PRMT5-AS1: 27.57% vs.18.30%, t=14.94, P<0.05). Knockdown of PRMT5-AS1 in HepG2 cells significantly increased cell death induced by IR (siNC vs. siPRMT5-AS1: 17.26% vs. 28.26%, t=13.63, P<0.05). Flow cytometry result show that overexpression of PRMT5-AS1 can significantly inhibit the increase of intracellular lipid ROS level induced by IR (Vector vs. PRMT5-AS1: 17.01% vs. 12.52%, t=12.80, P<0.05), and knockdown of PRMT5-AS1 significantly increases the lipid ROS level induced by IR (siNC vs. siPRMT5-AS1: 14.54% vs. 17.72%, t=5.93, P<0.05). The result of CCK-8 experiment showed that overexpression of PRMT5-AS1 could significantly inhibit Erastin induced cell activity reduction (Vector vs. PRMT5-AS1: 87.92% vs. 109.06%, t=2.87, P<0.05), and knockdown of PRMT5-AS1 could promote Erastin′s inhibitory effect on cell activity (siNC vs. siPRMT5-AS1: 82.56% vs. 60.58%, t=38.35, P<0.05). Western blot and fluorescent quantitative PCR result showed that the protein and mRNA levels of SLC7A11 were significantly increased after overexpression of PRMT5-AS1 ( t=26.24, P<0.05), and the protein and mRNA levels of SLC7A11 were significantly decreased after knockdown of PRMT5-AS1 ( t=5.60, P<0.05). The correlation between PRMT5-AS1 and let-7c-5p was confirmed by luciferase report gene experiment ( t=9.74, P<0.05). The result of luciferase reporter gene experiment showed that PRMT5-AS1 could form ceRNA network with let-7c-5p to regulate SLC7A11. Let-7c-5p was able to reverse the increase in SLC7A11 expression levels, decrease in Lipid-ROS levels and cell death induced by overexpression of PRMT5-AS1 ( t=3.01, 4.11, P<0.05). And knockdown of SLC7A11 reversed Lipid-ROS inhibition and reduced cell death caused by PRMT5-AS1( t=21.35, 7.15, P<0.05). Conclusions:LncRNA PRMT5-AS1 inhibits IR-induced ferroptosis in HCC through the PRMT5-AS1/let-7c-5p/SLC7A11 axis.
6.Epidemiological trend of notifiable infectious diseases in Yangpu District of Shanghai during 1950‒2020
Lu JI ; Lin WANG ; Shumei MA ; Xue HAN
Shanghai Journal of Preventive Medicine 2022;34(6):551-554
ObjectiveTo analyze the characteristics and trends of notifiable infectious diseases in Yangpu District of Shanghai, from 1950 to 2020, and to provide scientific basis for the formulation of control measures. MethodsDescriptive epidemiological method was used to collect and analyze the epidemiological data of notifiable infectious diseases. ResultsA total of 1 186 675 cases from 38 types of infectious diseases were reported. The annual morbidity of Class A and Class B infectious diseases fluctuated between 138.22/105 and 7 861.45/105, showing a decreasing trend. Among the 3 785 cases of death, the top five were measles, viral hepatitis, dysentery, tuberculosis and epidemic cerebrospinal meningitis. The high incidence diseases were intestinal infectious diseases, and the respiratory infectious diseases fluctuated in a wide range. Furthermore, blood-borne infectious diseases and sexual -transmitted diseases had continued to increase in recent years. As the result of normative vaccination, the incidence of associated infectious disease showed a downward trend. ConclusionThe incidence of infectious diseases in Yangpu District was on the drop from 1950 to 2020. Prevention and control work should focus on respiratory infectious diseases, blood-borne infectious diseases and sexual -transmitted diseases in the future. Furthermore, it is important to guarantee normative vaccination, especially, for prevention and control of infectious diseases.
7.Pathogenic characteristics of severe acute respiratory infection in adult inpatients in Yangpu District, Shanghai, 2019‒2021
Lu JI ; Fangfang TAO ; Lin WANG ; Jin XU ; Zhengbin XIAO ; Shumei MA
Shanghai Journal of Preventive Medicine 2022;34(8):774-779
ObjectiveTo understand the pathogenic spectrum and epidemiological characteristics of severe acute respiratory infection (SARI) in adult inpatients in Yangpu District, Shanghai, China, in order to explore strategies for the prevention and treatment of respiratory infectious diseases. MethodsIndividual cases were from adult inpatients with SARI in Yangpu District, Shanghai, China from January 2019 to July 2021. Their respiratory samples were collected for etiological pathogen testing. ResultsA total of 681 SARI cases were enrolled for sampling and lab testing. Among them, 79.00% were aged 60 years and older, and 75.48% had confirmed chronic disease history. A total of 163 infection inpatients (23.94%) were positive for at least one pathogen. The pathogens identified most frequently were influenza A virus (6.75%), followed by rhinovirus/enterovirus (3.23%), parainfluenza virus (PIV) (2.79%), Mycoplasma pneumoniae (2.35%), coronavirus (CoV) (2.06%). The positive rates of adenovirus (AdV), human metapneumovirus (hMPV), respiratory syncytial virus and bocavirus were all less than 2%. Bacterial strains were identified in eleven SARI cases, including Staphylococcus aureus and Pseudomonas aeruginosa (4 strains), Klebsiella pneumoniae (3 strains). Legionella pneumophila was detected in 9 cases (1.32%) and Bordetella pertussis in 5 cases (0.73%). Two pathogens were co-detected from 11 cases, accounting for 1.62% of 163 positive cases. The most common co-detected pathogens were influenza A virus and other pathogens, accounting for 54.55% of the mixed infection. The positive rates of pathogens were not significantly different between less than 60 years old and over 60 years old groups except for Bordetella pertussis, adenovirus and Mycoplasma pneumonia(P<0.05). Influenza virus had epidemic peak in winter and spring, but not in summer from 2019 to 2021. ConclusionVarious respiratory pathogens are detected from adult SARI cases. It is mainly influenza virus, with co-detected pathogens and rare pathogens. This study provides helpful information for targeted prevention and control measures including vaccination.
8.The application and value evaluation of assisted diagnosis system for five fundus lesion based on artificial intelligence combined with optical coherence tomography
Jian MA ; Shumei CHEN ; Min WANG ; Fuli WU ; Jian WU ; Xiaoyun FANG
Chinese Journal of Ocular Fundus Diseases 2022;38(2):126-131
Objective:To establish an artificial intelligence robot-assisted diagnosis system for fundus diseases based on deep learning optical coherence tomography (OCT) and evaluate its application value.Methods:Diagnostic test studies. From 2016 to 2019, 25 000 OCT images of 25 000 patients treated at the Eye Center of the Second Affiliated Hospital of Zhejiang University School of Medicine were used as training sets and validation sets for the fundus intelligent assisted diagnosis system. Among them, macular epiretinal membrane (MERM), macular edema, macular hole, choroidal neovascularization (CNV), and age-related macular degeneration (AMD) were 5 000 sheets each. The training set and the verification set are 18 124 and 6 876 sheets, respectively. Through the transfer learning Attention ResNet structure algorithm, the OCT image was characterized by lesion identification, the disease feature was extracted by a specific procedure, and the given image was distinguished from other types of disease according to the statistical characteristics of the target lesion. The model algorithms of MERM, macular edema, macular hole, CNV and AMD were initially formed, and the fundus intelligent auxiliary diagnosis system of five models was established. The performance of each model-assisted diagnosis in the fundus intelligent auxiliary diagnostic system was evaluated by applying the subject working characteristic curve, area under the curve (AUC), sensitivity, and specificity.Results:With the intelligent auxiliary diagnosis system, the diagnostic sensitivity of the MERM was 93.5%, the specificity was 99.23%, and AUC was 0.983 7; the diagnostic sensitivity of macular edema was 99.02%, the specificity was 98.17%, and AUC was 0.994 6; the diagnostic sensitivity of macular hole was 98.91%, the specificity was 99.91%, AUC was 0.996 2; the diagnostic sensitivity of CNV was 97.54%, the specificity was 94.71%, AUC was 0.987 5; the diagnostic sensitivity of AMD was 95.12%, the specificity was 97.09%, AUC was 0.985 3.Conclusions:The artificial intelligence robot-assisted diagnosis system for fundus diseases based on deep learning for OCT images has accurate and efficient diagnostic performance for assisting the diagnosis of MERM, macular edema, macular hole, CNV, and AMD.
9.Hepatectomy combined with radiofrequency ablation on liver cross section for hepatocellular carcinoma with microvascular invasion
Zhipeng TANG ; Dan ZHANG ; Jianwei QIN ; Zheng DANG ; Shulin XU ; Yuesheng LI ; Shumei XU ; Ganqing MA ; Ruifang FAN
Chinese Journal of General Surgery 2022;37(11):807-811
Objective:To evaluate radiofrequency ablation-assisted liver resection on early recurrence of hepatocellular carcinoma(HCC) with microvascular invasion (MVI).Methods:A total of 82 HCC patients from Jun 2015 to Jun 2020 were divided into assisted group ( n=41) and control group ( n=41) after local hepatectomy.And by pathology,both groups were further substratified into with or without MVI subgroups. Results:There was no statistically significant difference in the baseline data between two groups,nor there was difference in recurrence-free survival rate between the two groups ( χ 2=0.177, P=0.674). However, by subgroup analysis, the recurrence-free survival rate of ablation assisted group was higher than that of the simple local hepatectomy group among MVI positive patients ( χ 2=5.096, P = 0.024).Multivariate analysis showed that only tumor diameter ( HR=1.32, 95% CI: 1.02-1.72, P=0.036) was an independent risk factor for local recurrence at the incisal margin, while mode of operation ( HR=0.15 ,95% CI: 0.04-0.52 ,P=0.003) and MVI ( HR=8.65 ,95% CI: 2.19-34.19 ,P=0.002) were independent risk factors for intrahepatic distant metastasis. Conclusion:Local hepatectomy assisted by intraoperative radiofrequency ablation on hepatic cross section could effectively reduce the postoperative early recurrence rate for hepatocellular carcinoma patients with MVI.
10.Observation on the structural characteristics of optic discs in high myopia combined with primary open-angle glaucoma
Jie ZHOU ; Yuxin ZHANG ; Jing DENG ; Peilin ZHONG ; Shumei WANG ; Jia MA
Chinese Journal of Ocular Fundus Diseases 2022;38(6):468-477
Objective:To observe and analyze the structural characteristics of the optic discs in high myopia (HM) combined with primary open-angle glaucoma (POAG) and the optic disc parameters with diagnostic efficacy.Methods:A cross-sectional study. From August 2020 to March 2021, a total of 114 eyes of 68 patients with POAG, HM and healthy volunteers who were diagnosed by Department of Ophthalmology, The First Affiliated Hospital of Kunming Medical University were included in the study. Among them, 21 POAG patients (39 eyes) were divided into H+P group (9 patients, 18 eyes) and non-H+P group (12 patients, 21 eyes) according to whether or not HM was combined; 26 HM patients (37 eyes) were selected as HM group; 21 healthy volunteers (38 eyes) were selected as normal control group. The subjects included 31 males (51 eyes) and 37 females (63 eyes), whose average age was 36.93±12.60 years old. Diopter, central corneal thickness (CCT) and axial length (AL) were measured. There was no significant difference in age ( F=8.333), sex composition ratio ( χ2=0.863), and CCT ( F=1.425) among the four groups ( P>0.05); while, there were significant differences in AL ( F=69.956), diopter ( F=37.711), visual field index (VFI) ( F=43.254) and mean defect (MD) ( F=49.793) among the four groups ( P<0.01). Enhanced depth imaging using optical coherence tomography was used to obtain the tilt parameters, the disc rim parameters, the lamina cribrosa parameters and the retinal nerve fiber layer (RNFL) thickness. The tilt parameters included optic disc horizontal diameter, optic disc vertical diameter, optic disc ellipse index (horizontal diameter/vertical diameter); the disc rim parameters included Bruch’s membrane opening-minimal rim width (BMO), optic cup area, optic disc area, disc rim area, cup-disc area ratio; the lamina cribrosa parameters included anterior laminar insertion depth (ALID), prelaminar neural tissue (PLNT), and lamina cribrosa thickness. The pairwise comparison between groups were performed by ANOVA test. Pearson correlation analysis was used to analyze the correlation between disc tilt parameters, disc rim parameters, lamina cribrosa parameters and visual field parameters, as well as between disc rim parameters and RNFL thickness. According to receiver operating characteristic (ROC) curve and area under the curve (AUC), the predictive value of those above related factors for HM combined with POAG was evaluated. Results:Tilt parameters: compared with the optic disc horizontal diameter of non-H+P group, those of normal control group, HM group and H+P group were significantly decreased ( P<0.05), the ellipse indices of HM group and H+P group were significantly lower than those of normal control group and non-H+P group ( P<0.05). The results of correlation analysis showed that the optic disc horizontal and vertical diameters were negatively correlated with MD ( r=-0.302,-0.235; P=0.002, 0.017), and negatively correlated with VFI ( r=-0.291,-0.246; P=0.003, 0.013). Disc rim parameters: the disc cup area and cup-disc area ratio of non-H+P group and H+P group were significantly larger than those of normal control group and HM group ( P<0.05). The disc rim area and the average BMO of HM group, non-H+P group and H+P group were significantly smaller than those of normal control group ( P<0.05). The results of correlation analysis showed that the cup-disc area ratio ( r=-0.584), the average BMO ( r=0.650) had the highest correlation with the average RNFL thickness ( P<0.001). The superior, inferior, nasal and temporal BMO were all positively correlated with the corresponding quadrant RNFL thicknesses ( r=0.431, 0.656, 0.362, 0.375; P<0.05); the optic disc rim area, the average BMO were positively correlated with MD ( r=0.449, 0.618) and VFI ( r=0.449, 0.605) ( P<0.05), among which the correlation of the average BMO was the highest; the optic cup area and cup-disc area ratio were negatively correlated with MD ( r=-0.346,-0.559) and VFI ( r=-0.312,-0.548) ( P<0.001), among which the correlation of the cup-disc area ratio was the highest. Lamina cribrosa parameters: ALID of non-H+P group and H+P group were significantly deeper than those of normal control group and HM group ( P<0.05). LC of non-H+P group and H+P group were significantly thinner than those of normal control group and HM group ( P<0.05). The results of correlation analysis showed that ALID was negatively correlated with MD and VFI ( r=-0.402, P<0.001), VFI ( r=-0.405, P=0.001); LC was positively correlated with MD and VFI ( r=0.403, P<0.001), VFI ( r=-0.401, P=0.015). Comparison of diagnostic efficiency between various optic disc parameters: the results of ROC analysis showed that the cup-disc area ratio had the highest diagnostic performance (AUC=0.847, P=0.007), the maximum Youden index was 0.563, the sensitivity and specificity were 0.833 and 0.730, respectively, and the best critical value was 0.340. Conclusions:Optic disc tilt is more pronounced in HM combined with POAG; BMO in each quadrant could objectively reflect the disc rim defect of HM combined with POAG; the thinning and the backward shift of the lamina cribrosa were consistent with the aggravation of the visual field defect. Among them, the cup-disc area ratio had better diagnostic performance.


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