1.Evaluation of colistin sulfate administration regimen based on PK/PD theory and Monte Carlo simulation
Yingchao MA ; Xia WU ; Yongjing WANG ; Jianjun GU ; Xiuling YANG
China Pharmacy 2025;36(4):459-463
OBJECTIVE To evaluate the therapeutic efficacy of 5 regimens of colistin sulfate for common Gram-negative bacilli infection based on pharmacokinetics (PK)/pharmacodynamics (PD) theory and Monte Carlo simulation. METHODS Minimal inhibitory concentration (MIC) data of colistin sulfate against Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli and Enterobacter cloacae in 2023 were collected from the China Antimicrobial Resistance Surveillance System. Monte Carlo simulation was conducted with the ratio of the area under the concentration-time curve from 0 to 24 hours in the unbound state to the MIC (fAUC0-24 h/MIC) ≥15 as the target value, the probabilities of target attainment (PTA) of 5 regimens of colistin sulfate to achieve the target ratio were obtained at different MIC; and the expected population PTA, specifically the cumulative fraction of response (CFR), for each regimen within a specific bacterial population was further calculated, to evaluate the therapeutic efficacy of the five colistin sulfate regimens. RESULTS When bacterial MIC≤0.5 µg/mL, PTA of all colistin sulfate regimens (500 000 IU, q12 h; 500 000 IU, q8 h; 750 000 IU, q12 h; 750 000 IU, q8 h; 1 000 000 IU, q12 h) were all more than 90%. When bacterial MIC=1 µg/mL, PTA for regimen (750 000 IU, q8 h) against A. baumannii, K. pneumoniae, P. aeruginosa, E. coli and E. cloacae, and for regimen (1 000 000 IU, q12 h) against the other four bacterial species (excluding P. aeruginosa) remained above 90%. When bacterial MIC≥2 µg/mL, PTA of 5 colistin sulfate regimens were all lower than 90%. For E. coli, the CFR of only colistin sulfate regimen (500 000 IU, q12 h) was less than 90%; for K. pneumoniae, the CFR of only colistin sulfate regimen (750 000 IU, q8 h and 1 000 000 IU, q12 h) was greater than 90%; for the other three bacteria, CFR of 5 regimens were all less than 90%. CONCLUSIONS When the MIC of Gram-negative bacteria is less than 0.5 µg/mL, colistin sulfate regimen with a routine dose can be selected for treatment. When MIC was 1 µg/mL, an increase in the dosing amount or frequency is required. The empirical treatment of the other four bacterial infections excluding E. coli requires the use of off-label doses.
2.Immune reconstitution and influencing factors in HIV infected men who have sex with men with access to antiviral therapy in Guangxi Zhuang Autonomous Region from 2005 to 2021
Ni CHEN ; He JIANG ; Huanhuan CHEN ; Qiuying ZHU ; Xiuling WU ; Jianjun LI ; Nengxiu LIANG ; Qin MENG ; Xuanhua LIU ; Jinghua HUANG ; Wenxuan HOU ; Zhaoquan WANG ; Guanghua LAN
Chinese Journal of Epidemiology 2024;45(4):529-535
Objective:To analyze immune reconstitution and influencing factors in HIV infected men who have sex with men (MSM) with access to antiviral therapy (ART) in Guangxi Zhuang Autonomous Region (Guangxi) during 2005-2021.Methods:The data were collected from Chinese Disease Prevention and Control Information System. The study subjects were HIV infected MSM with access to the initial ART for ≥24 weeks in Guangxi from 2005 to 2021 and HIV RNA lower than the detection limit within 24 months. The proportion of infected MSM who had immune reconstitution after ART was calculated. Cox proportional hazard regression model was used to analyze the influencing factors of immune reconstitution. Software SPSS 24.0 was used for statistical analysis.Results:A total of 3 200 HIV infected MSM were enrolled, in whom 15.56 % (498/3 200) had no immune reconstitution, 14.78% (473/3 200) had moderate immune reconstitution, and the rate of complete immune reconstitution was 69.66% (2 229/3 200). The M ( Q1, Q3) of ART time for immune reconstitution was 12 (5, 27) months. Multivariate Cox proportional risk regression model analysis results showed that compared with those with initial ART at age ≥30 years, WHO clinical stage Ⅲ/Ⅳ illness, baseline BMI <18.50 kg/m 2 and baseline CD4 +T lymphocyte (CD4) counts <200 cells/μl, HIV infected MSM with initial ART at age <30 years, WHO clinical stageⅠ/Ⅱ illness, baseline BMI≥24.00 kg/m 2 and baseline CD4 counts ≥200 cells/μl were more likely to have complete immune reconstitution. Conclusions:In the HIV infected MSM in Guangxi, failures to achieve moderate and complete immune reconstitution were observed. Surveillance and ART regimen should be improved for key populations, such as those with older age and low baseline CD4 counts.
3.Relationship among psychological resilience, parental control, and behavioral problems in junior high school students in Guizhou Province
Chinese Journal of School Health 2024;45(5):689-692
Objective:
To investigate the relationships among psychological resilience, parental control, and behavioral problems in middle school students, aiming to provide evidencebased recommendations for the prevention and intervention of behavioral issues in middle school students, as well as for the development of related policies.
Methods:
A stratified cluster sampling method was used to select 2 745 participants from three cities in Guizhou Province with different levels of economic development from August to December 2021. The Child Behavior Checklist (CBCL), Parental Control Questionnaire, and Psychological Resilience Questionnaire were administered to junior high school students and their parents. A network analysis method was employed to construct a network analysis model of factors influencing behavioral problems.
Results:
The detection rate of behavioral problems among junior high school students in Guizhou Province was 22.62%. The scores for psychological resilience (goal focus, emotional control, positive cognition, family support, and interpersonal assistance) and proactive inquiry in behavior control were higher in the group without behavioral problems than in the group with behavioral problems. Scores for psychological control (inducing guilt, with drawing affection, and asserting authority) were higher in the group with behavioral problems than in the group without behavioral problems, with statistically significant differences (t=9.80, 17.76, 6.21, 12.20, 13.18, 6.28, 11.58, 11.10, 10.74, P<0.05). The network model showed that among the same variable factors, the strongest connection weight was between inducing guilt and withdrawing affection, with a weight of 0.79. Between different variables, there were negative correlation between behavioral problems and psychological resilience (goal focus, emotional control, positive cognition, family support, interpersonal assistance) and behavior control (proactive inquiry, behavioral restraint) with correlation coefficients (r=-0.25, -0.42, -0.16, -0.31, -0.33, -0.17, -0.03, P<0.05), respectively. There were positive correlation between psychological control factors (inducing guilt, withdrawing affection, and asserting authority) and behavioral problems (r=0.29, 0.27, 0.27), and a negative correlation between these psychological control factors and psychological resilience factors (goal focus, emotional control, positive cognition, family support, interpersonal assistance)(r=-0.53--0.13)(P<0.05). The strongest connection weight was between withdrawing affection and family support, with a connection weight of -0.53. Family support was an important bridge symptom connecting the entire behavioral problem network model, with a high centrality.
Conclusions
The detection rate of behavioral problems among junior high school students in Guizhou Province is relatively high. Assisting adolescents in establishing a supportive family environment facilitates the cultivation of their psychological resilience, thereby mitigating the occurrence of behavioral problems.
4.Hederagenin alleviates neuroinflammation response by regulating glutamate-induced ferroptosis in HT22 cells
Yuxin FENG ; Heran WANG ; Yazhuo HU ; Hongmei SUN ; Xiaoxue ZHANG ; Xiuling MIAO ; Zihan LI ; Jianjun JIA
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2024;26(10):1221-1225
Objective To explore the regulatory role of hederagenin(HG)on glutamate(Glu)-in-duced ferroptosis and corresponding inflammatory responses in mouse hippocampal neuron HT22 cells and investigate its potential mechanisms.Methods HT22 cells were randomly divided into control,Glu and HG groups(n=3).The cells of the control group received no treatment,the cells of the Glu group were treated with 35 mmol/L Glu for 24 h to establish a cellular model of ferroptosis in Alzheimer's disease,and the cells of the HG group were treated with 0.5 μmol/L HG and 35 mmol/L Glu for 24 h simultaneously.FerroOrange fluorescent probe was used to de-tect intracellular Fe2+.The production of reactive oxygen species(ROS),mitochondrial membrane potential,and levels of inflammatory factors TNF-α,IL-1β and IL-6 in the cells were assessed.Finally,the expression of the key regulator of iron death,glutathione peroxidase 4(GPX4)was measured.Results Compared to the control group,the levels of intracellular Fe2+,ROS,TNF-α,IL-1β,and IL-6 were significantly elevated,while the mitochondrial membrane potential was obvi-ously reduced in the Glu group(P<0.05,P<0.01).The HG group had significantly decreased Fe2+,ROS,TNF-α,IL-1β,and IL-6 and enhanced mitochondrial membrane potential than the Glu group(P<0.05,P<0.01).The GPX4 expression was significantly lower in the Glu group than the control group(1.00±0.02 vs 0.46±0.04,P<0.01),and was notably higher in the 0.5 and 1.0 μmol/L HG groups when compared to the Glu group(0.64±0.03 and 0.59±0.05 vs 0.46±0.04,P<0.01).Conclusion HG inhibits ferroptosis by regulating GPX4 expression,and thereby effec-tively alleviates the inflammatory response.
5.Application value of prediction model based on magnetic resonance imaging machine learning algorithm and radiomics in predicting lymphovascular invasion status of rectal cancer with-out lymph node metastasis
Leping PENG ; Xiuling ZHANG ; Yuanhui ZHU ; Ling WANG ; Wenting MA ; Yaqiong MA ; Gang HUANG ; Lili WANG
Chinese Journal of Digestive Surgery 2024;23(8):1099-1111
Objective:To construct an prediction model based on magnetic resonance imaging (MRI) machine learning algorithm and radiomics and investigate its application value in predicting lymphovascular invasion (LVI) status of rectal cancer without lymph node metastasis.Methods:The retrospective cohort study was conducted. The clinicopathological data of 204 rectal cancer patients without lymph node metastasis who were admitted to Gansu Provincial Hospital from February 2016 to January 2024 were collected. There were 123 males and 81 females, aged (61±7)years. All 204 patients were randomly divided into the training dataset of 163 cases and the testing dataset of 41 cases by a ratio of 8∶2 using the electronic computer randomization method. The training dataset was used to construct the prediction model, and the testing dataset was used to validate the prediction model. The clinical prediction model, radiomics model and joint prediction model were constructed based on the selected clinical and/or imaging features. Measurement data with normal distribution were represented as Mean± SD. Count data were described as absolute numbers, and the chi-square test or Fisher exact probability were used for comparison between the groups. Comparison of ordinal data was conducted using the nonparameter rank sum test. The inter-class correlation coefficient (ICC) was used to evaluate the consistency of the radiomics features of the two doctors, and ICC >0.80 was good consistency. Univariate analysis was conducted by corres-ponding statistic methods. Multivariate analysis was conducted by Logistic stepwise regression model. The receiver operating characteristic (ROC) curve was drawn, and the area under the curve (AUC), Delong test, decision curve and clinical impact curve were used to evaluate the diagnostic efficiency and clinical utility of the model. Result:(1) Analysis of factors affecting LVI status of patients. Of the 204 rectal cancer patients without lymph node metastasis, there were 71 cases with positive of LVI and 133 cases with negative of LVI. Results of multivariate analysis showed that gender, platelet (PLT) count and carcinoembryonic antigen (CEA) were independent factors affecting LVI status of rectal cancer without lymph node metastasis in training dataset [ odds ratio=2.405, 25.062, 2.528, 95% confidence interval ( CI) as 1.093-5.291, 2.748-228.604, 1.181-5.410, P<0.05]. (2) Construction of clinical prediction model. The clinical prediction model was conducted based on the results of multivariate analysis including gender, PLT count and CEA. Results of ROC curve showed that the AUC, accuracy, sensitivity and specificity of clinical prediction model were 0.721 (95% CI as 0.637-0.805), 0.675, 0.632 and 0.698 for the training dataset, and 0.795 (95% CI as 0.644-0.946), 0.805, 1.000 and 0.429 for the testing dataset. Results of Delong test showed that there was no significant difference in the AUC of clinical prediction model between the training dataset and the testing dataset ( Z=-0.836, P>0.05). (3) Construction of radiomics model. A total of 851 radiomics features were extracted from 204 patients, and seven machine learning algorithms, including logistic regression, support vector machine, Gaussian process, logistic regression-lasso algorithm, linear discriminant analysis, naive Bayes and automatic encoder, were used to construct the prediction model. Eight radiomics features were finally selected from the optimal Gaussian process learning algorithm to construct a radiomics prediction model. Results of ROC curve showed that the AUC, accuracy, sensitivity and specificity of radiomics prediction model were 0.857 (95% CI as 0.800-0.914), 0.748, 0.947 and 0.642 for the training dataset, and 0.725 (95% CI as 0.571-0.878), 0.634, 1.000 and 0.444 for the testing dataset. Results of Delong test showed that there was no significant difference in the AUC of radiomics prediction model between the training dataset and the testing dataset ( Z=1.578, P>0.05). (4) Construction of joint prediction model. The joint prediction model was constructed based on the results of multivariate analysis and the radiomics features. Results of ROC curve showed that the AUC, accuracy, sensitivity and specificity of radiomics prediction model were 0.885 (95% CI as 0.832-0.938), 0.791, 0.912 and 0.726 for the training dataset, and 0.857 (95% CI as 0.731-0.984), 0.854, 0.714 and 0.926 for the testing dataset. Results of Delong test showed that there was no significant difference in the AUC of joint prediction model between the training dataset and the testing dataset ( Z=0.395, P>0.05). (5) Performance comparison of three prediction models. Results of the Hosmer-Lemeshow goodness-of-fit test showed that all of the clinical prediction model, radiomics prodiction model and joint prediction model having good fitting degree ( χ2=1.464, 12.763, 10.828, P>0.05). Results of Delong test showed that there was no signifi-cant difference in the AUC between the clinical prediction model and the joint prediction model or the radiomics model ( Z=1.146, 0.658, P>0.05), and there was a significant difference in the AUC between the joint prediction model and the radiomics model ( Z=2.001, P<0.05). Results of calibra-tion curve showed a good performance in the joint prediction model. Results of decision curve and clinical impact curve showed that the performance of joint prediction model in predicting LVI status of rectal cancer without lymph node metastasis was superior to the clinical prediction model and the radiomics model. Conclusions:The clinical prediction model is constructed based on gender, PLT count and CEA. The radiomics predictive model is constructed based on 8 selected radiomics features. The joint prediction model is constructed based on the clinical prediction model and the radiomics predictive model. All of the three models can predict the LVI status of rectal cancer with-out lymph node metastasis, and the joint prediction model has a superior predictive performance.
6.Clinical application of endoscopic resection using snares in treatment of gastric submucosal tumors
Manman LU ; Zhenjuan LI ; Shanshan XU ; Huimin ZHANG ; Xueyan WANG ; Jiaxin LI ; Runzhao QUAN ; Hao ZHANG ; Hui DING ; Xiuling LI
China Journal of Endoscopy 2024;30(11):39-46
Objective To investigate the clinical efficacy and safety of endoscopic resection using snares for the treatment of gastric submucosal tumors(SMTs).Methods 66 patients diagnosed with gastric SMTs and treated with endoscopic resection from August 2017 to August 2023 were retrospectively analyzed and divided into the snare group(endoscopic resection using snares,n=33)and the traditional resection group(endoscopic resection using a traditional disposable incision knife,n=33).The operation time,overall resection rate,incidence of adverse reactions,operation cost,hospitalisation cost,and the post-operative hospital days were compared between the two groups.Results The lesion diameter was 8.00(6.00,14.00)mm in the snare group and 8.00(7.50,10.00)mm in the traditional resection group,the difference between the two groups was not statistically significant(P>0.05);The operative time in the snare group was significantly shorter than that in the traditional resection group[26.00(19.00,30.50)min vs 33.00(22.50,49.50)min],the difference was statistically significant(P<0.05);The overall resection rate in both groups was 100.0%;Neither group of patients had intraoperative perforation.There were no statistically significant differences in the incidence of adverse reactions such as intraoperative bleeding,abdominal pain and fever between the two group(P>0.05);The operative cost of the snare group was significantly lower than the traditional endoscopic resection group[(8 642.18±1 078.56)yuan vs(13 266.45±2 160.80)yuan],the difference was statistically significant(P<0.05).Conclusion Compared with traditional surgical instruments,endoscopic resection of gastric SMTs using snares has a shorter operating time,lower surgical costs,safe and effective,making it worthy of promotion.
7.Application of multidisciplinary family empowerment mode in home care for patients after percutaneous endoscopic gastrostomy
Yu LI ; Zhicheng HUANG ; Haili FANG ; Jing YANG ; Caixia MOU ; Lijuan WANG ; Yanjiang LIU ; Xiuling ZHOU
Journal of Interventional Radiology 2024;33(11):1234-1238
Objective To discuss the effect of multidisciplinary family empowerment mode in home care for patients after receiving percutaneous endoscopic gastrostomy(PEG).Methods A total of 86 patients,who received initial PEG at the Jilin Provincial Cancer Hospital of China from January 2021 to July 2023,were selected for this study.The patients were randomly divided into observation group.The patients of the control group received routine nursing guidance for gastrostomy,while the patients of the observation group received multidisciplinary family empowerment nursing mode.The self-care ability[using self-care ability scale of the elderly(SASE)score],health behavior ability[using self-rating scale of health behavior ability(SRAHP)score],incidence of complications,and healing time of complications were compared between the two groups.Results In the observation group the SASE[(129.48±5.48)points vs.(73.05±12.04)points]and the SRAHP[(80.14±1.00)points vs.(70.25±7.92)points]were significantly higher than those in the control group(all P<0.05),the incidence of complications was lower than that in the control group,and the healing time of complications was shorter than that in the control group.Conclusion The implementation of multidisciplinary family empowerment nursing mode can improve the self-care ability and health behavior ability of patients after receiving PEG,reduce postoperative complications,as well as shorten the healing time of complications,therefore,this nursing mode is suitable for home patients after receiving PEG.
8.Effects of long non-coding RNA H19 regulating miRNA-675 and PTEN on the cell proliferation of glioma
Ping LIU ; Ningning ZHANG ; Ying ZHANG ; Ranxin HUANG ; Yuexiang ZHANG ; Lulu LI ; Zemin QIN ; Xiuling WANG ; Sulan WANG ; Jianlan CHANG ; Junyan YU
Cancer Research and Clinic 2024;36(11):863-868
Objective:To investigate the effect of long non-coding RNA (lncRNA) H19 regulating miRNA-675 (miR-675) and phosphatase and tensin homologue-deleted chromosome ten gene (PTEN) on the cell proliferation of glioma.Methods:Glioma cell lines U87-MG and U251 were chosen. The siRNA online design tool wad used to design small interfering RNA (siRNA) targeting H19. U87-MG and U251 cell lines with the stable knockdown of H19 were constructed (the stable knockdown of H19 group), and the cells randomly transfected with siRNA plasmid were taken as the control group, and normal cultured cells were treated as the blank group. Additionally, miR-675 and control microRNA were transfected into U87-MG and U251 with the stable knockdown of H19 (the overexpressing miR-675 group and the corresponding control group). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the relative expression levels of miR-675 and H19 in each group; the methyl thiazolyl tetrazolium (MTT) assay was used to detect the cell proliferation ability; the dual luciferase reporter gene assay was used to verify the targeting relationship between miR-675 and PTEN; Western blot was used to detect the relative expression level of PTEN protein.Results:The MTT assay results showed that the proliferation ability of U87-MG and U251 cells in the stable knockdown of H19 group was lower than that of the corresponding control group; and the differences in cell proliferation ability of all the groups after 48 h of culture were statistically significant (all P < 0.05). qRT-PCR detection results showed that the relative expression level of miR-675 in U251 cells in the stable knockdown of H19 group and the corresponding control group was 0.329±0.009 and 1.043±0.087, respectively, and the difference was statistically significant ( t = 14.15, P < 0.001); the relative expression level of miR-675 in U87-MG cells in the stable knockdown of H19 group and the corresponding control group was 0.299±0.009 and 1.027±0.106, respectively, and the difference was statistically significant ( t = 11.85, P < 0.001); the relative expression level of miR-675 in U87-MG and U251 cells in the stable knockdown of H19 group was lower than that of the corresponding control group. The dual luciferase reporter gene assay verified that miR-675 could bind to the 3'-UTR of PTEN. Western blot detection results showed that the relative expression level of PTEN protein in U87-MG and U251 cells in the stable knockdown of H19 group was higher than that of the corresponding control group and the blank group; in the U87-MG and U251 cells in the stable knockdown of H19 group, the relative expression level of PTEN in the overexpressing miR-675 group was lower than that of the corresponding blank group and the control group. In the U87-MG and U251 cells in the stable knockdown of H19 group, the cell proliferation ability of the overexpressing miR-675 group was higher than that of the corresponding blank group and the control group; the differences in cell proliferation ability of all the groups after 48 h of culture were statistically significant (all P < 0.05). Conclusions:lncRNA H19 may regulate the cell proliferation of glioma cells through the miR-675-PTEN signaling pathway.
9.Risk factors analysis and nomogram construction of facial pressure injury related to ventilation in prone positioning in children with severe pneumonia
Xiuling ZHAI ; Yongxia WANG ; Hui DING ; Libing ZHANG ; Mei LI
Journal of Clinical Medicine in Practice 2024;28(4):102-106
Objective To investigate the influencing factors of facial pressure injury related to ventilation in prone positioning in children with severe pneumonia and to construct a nomogram prediction model. Methods A total of 158 children with severe pneumonia who underwent prone positioning ventilation were selected as research subjects. Clinical data were collected, and the children were divided into injury group (31 cases) and non-injury group (127 cases) based on whether facial pressure injury occurred. Univariate and multivariate Logistic regression analysis were used to explore the influencing factors of facial pressure injury related to prone positioning ventilation in children with severe pneumonia; the receiver operating characteristic (ROC) curve, consistency index, and Hosmer-Lemeshow goodness-of-fit test were used to evaluate the predictive efficiency of the nomogram model for facial pressure injury related to prone positioning ventilation in children with severe pneumonia. Results Univariate analysis showed that the proportion of children aged < 3 years, the proportion of those with complications, ventilation time in prone positioning, the proportions of children with sedative drugs and poor nutritional status, no decompression dressings, and the proportions of children without prone positioning ventilation training for medical staff in the injury group were higher or longer than that in the non-injury group (
10.Estrogen upregulates DNA2 expression through the PI3K-AKT pathway in endometrial carcinoma.
Xinyan WANG ; Xiuling XU ; Ting ZHANG ; Yang JIN ; Sheng XU ; Lifeng CHEN ; Yucheng LAI ; Ling ZHANG ; Ruolang PAN ; Yan YU
Journal of Zhejiang University. Science. B 2023;24(3):262-268
Endometrial cancer is the most common gynecological malignancy, affecting up to 3% of women at some point during their lifetime (Morice et al., 2016; Li and Wang, 2021). Based on the pathogenesis and biological behavioral characteristics, endometrial cancer can be divided into estrogen-dependent (I) and non-estrogen-dependent (II) types (Ulrich, 2011). Type I accounts for approximately 80% of cases, of which the majority are endometrioid carcinomas, and the remaining are mucinous adenocarcinomas (Setiawan et al., 2013). It is generally recognized that long-term stimulation by high estrogen levels with the lack of progesterone antagonism is the most important risk factor; meanwhile, there is no definite conclusion on the specific pathogenesis. The incidence of endometrial cancer has been on the rise during the past two decades (Constantine et al., 2019; Gao et al., 2022; Luo et al., 2022). Moreover, the development of assisted reproductive technology and antiprogestin therapy following breast cancer surgery has elevated the risk of developing type I endometrial cancer to a certain extent (Vassard et al., 2019). Therefore, investigating the influence of estrogen in type I endometrial cancer may provide novel concepts for risk assessment and adjuvant therapy, and at the same time, provide a basis for research on new drugs to treat endometrial cancer.
Female
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Humans
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Proto-Oncogene Proteins c-akt
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Phosphatidylinositol 3-Kinases
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Endometrial Neoplasms
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Estrogens
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Breast Neoplasms
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DNA Helicases


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