1.Application of CRISPR/Cas System in Precision Medicine for Triple-negative Breast Cancer
Hui-Ling LIN ; Yu-Xin OUYANG ; Wan-Ying TANG ; Mi HU ; Mao PENG ; Ping-Ping HE ; Xin-Ping OUYANG
Progress in Biochemistry and Biophysics 2025;52(2):279-289
Triple-negative breast cancer (TNBC) represents a distinctive subtype, characterized by the absence of estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2 (HER2). Due to its high inter-tumor and intra-tumor heterogeneity, TNBC poses significant chanllenges for personalized diagnosis and treatment. The advant of clustered regular interspaced short palindromic repeats (CRISPR) technology has profoundly enhanced our understanding of the structure and function of the TNBC genome, providing a powerful tool for investigating the occurrence and development of diseases. This review focuses on the application of CRISPR/Cas technology in the personalized diagnosis and treatment of TNBC. We begin by discussing the unique attributes of TNBC and the limitations of current diagnostic and treatment approaches: conventional diagnostic methods provide limited insights into TNBC, while traditional chemotherapy drugs are often associated with low efficacy and severe side effects. The CRISPR/Cas system, which activates Cas enzymes through complementary guide RNAs (gRNAs) to selectively degrade specific nucleic acids, has emerged as a robust tool for TNBC research. This technology enables precise gene editing, allowing for a deeper understanding of TNBC heterogeneity by marking and tracking diverse cell clones. Additionally, CRISPR facilitates high-throughput screening to promptly identify genes involved in TNBC growth, metastasis, and drug resistance, thus revealing new therapeutic targets and strategies. In TNBC diagnostics, CRISPR/Cas was applied to develop molecular diagnostic systems based on Cas9, Cas12, and Cas13, each employing distinct detection principles. These systems can sensitively and specifically detect a variety of TNBC biomarkers, including cell-specific DNA/RNA and circulating tumor DNA (ctDNA). In the realm of precision therapy, CRISPR/Cas has been utilized to identify key genes implicated in TNBC progression and treatment resistance. CRISPR-based screening has uncovered potential therapeutic targets, while its gene-editing capabilities have facilitated the development of combination therapies with traditional chemotherapy drugs, enhancing their efficacy. Despite its promise, the clinical translation of CRISPR/Cas technology remains in its early stages. Several clinical trials are underway to assess its safety and efficacy in the treatment of various genetic diseases and cancers. Challenges such as off-target effects, editing efficiency, and delivery methods remain to be addressed. The integration of CRISPR/Cas with other technologies, such as 3D cell culture systems, human induced pluripotent stem cells (hiPSCs), and artificial intelligence (AI), is expected to further advance precision medicine for TNBC. These technological convergences can offer deeper insights into disease mechanisms and facilitate the development of personalized treatment strategies. In conclusion, the CRISPR/Cas system holds immense potential in the precise diagnosis and treatment of TNBC. As the technology progresses and becomes more costs-effective, its clinical relevance will grow, and the translation of CRISPR/Cas system data into clinical applications will pave the way for optimal diagnosis and treatment strategies for TNBC patients. However, technical hurdles and ethical considerations require ongoing research and regulation to ensure safety and efficacy.
2.Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients (version 2024)
Yao LU ; Yang LI ; Leiying ZHANG ; Hao TANG ; Huidan JING ; Yaoli WANG ; Xiangzhi JIA ; Li BA ; Maohong BIAN ; Dan CAI ; Hui CAI ; Xiaohong CAI ; Zhanshan ZHA ; Bingyu CHEN ; Daqing CHEN ; Feng CHEN ; Guoan CHEN ; Haiming CHEN ; Jing CHEN ; Min CHEN ; Qing CHEN ; Shu CHEN ; Xi CHEN ; Jinfeng CHENG ; Xiaoling CHU ; Hongwang CUI ; Xin CUI ; Zhen DA ; Ying DAI ; Surong DENG ; Weiqun DONG ; Weimin FAN ; Ke FENG ; Danhui FU ; Yongshui FU ; Qi FU ; Xuemei FU ; Jia GAN ; Xinyu GAN ; Wei GAO ; Huaizheng GONG ; Rong GUI ; Geng GUO ; Ning HAN ; Yiwen HAO ; Wubing HE ; Qiang HONG ; Ruiqin HOU ; Wei HOU ; Jie HU ; Peiyang HU ; Xi HU ; Xiaoyu HU ; Guangbin HUANG ; Jie HUANG ; Xiangyan HUANG ; Yuanshuai HUANG ; Shouyong HUN ; Xuebing JIANG ; Ping JIN ; Dong LAI ; Aiping LE ; Hongmei LI ; Bijuan LI ; Cuiying LI ; Daihong LI ; Haihong LI ; He LI ; Hui LI ; Jianping LI ; Ning LI ; Xiying LI ; Xiangmin LI ; Xiaofei LI ; Xiaojuan LI ; Zhiqiang LI ; Zhongjun LI ; Zunyan LI ; Huaqin LIANG ; Xiaohua LIANG ; Dongfa LIAO ; Qun LIAO ; Yan LIAO ; Jiajin LIN ; Chunxia LIU ; Fenghua LIU ; Peixian LIU ; Tiemei LIU ; Xiaoxin LIU ; Zhiwei LIU ; Zhongdi LIU ; Hua LU ; Jianfeng LUAN ; Jianjun LUO ; Qun LUO ; Dingfeng LYU ; Qi LYU ; Xianping LYU ; Aijun MA ; Liqiang MA ; Shuxuan MA ; Xainjun MA ; Xiaogang MA ; Xiaoli MA ; Guoqing MAO ; Shijie MU ; Shaolin NIE ; Shujuan OUYANG ; Xilin OUYANG ; Chunqiu PAN ; Jian PAN ; Xiaohua PAN ; Lei PENG ; Tao PENG ; Baohua QIAN ; Shu QIAO ; Li QIN ; Ying REN ; Zhaoqi REN ; Ruiming RONG ; Changshan SU ; Mingwei SUN ; Wenwu SUN ; Zhenwei SUN ; Haiping TANG ; Xiaofeng TANG ; Changjiu TANG ; Cuihua TAO ; Zhibin TIAN ; Juan WANG ; Baoyan WANG ; Chunyan WANG ; Gefei WANG ; Haiyan WANG ; Hongjie WANG ; Peng WANG ; Pengli WANG ; Qiushi WANG ; Xiaoning WANG ; Xinhua WANG ; Xuefeng WANG ; Yong WANG ; Yongjun WANG ; Yuanjie WANG ; Zhihua WANG ; Shaojun WEI ; Yaming WEI ; Jianbo WEN ; Jun WEN ; Jiang WU ; Jufeng WU ; Aijun XIA ; Fei XIA ; Rong XIA ; Jue XIE ; Yanchao XING ; Yan XIONG ; Feng XU ; Yongzhu XU ; Yongan XU ; Yonghe YAN ; Beizhan YAN ; Jiang YANG ; Jiangcun YANG ; Jun YANG ; Xinwen YANG ; Yongyi YANG ; Chunyan YAO ; Mingliang YE ; Changlin YIN ; Ming YIN ; Wen YIN ; Lianling YU ; Shuhong YU ; Zebo YU ; Yigang YU ; Anyong YU ; Hong YUAN ; Yi YUAN ; Chan ZHANG ; Jinjun ZHANG ; Jun ZHANG ; Kai ZHANG ; Leibing ZHANG ; Quan ZHANG ; Rongjiang ZHANG ; Sanming ZHANG ; Shengji ZHANG ; Shuo ZHANG ; Wei ZHANG ; Weidong ZHANG ; Xi ZHANG ; Xingwen ZHANG ; Guixi ZHANG ; Xiaojun ZHANG ; Guoqing ZHAO ; Jianpeng ZHAO ; Shuming ZHAO ; Beibei ZHENG ; Shangen ZHENG ; Huayou ZHOU ; Jicheng ZHOU ; Lihong ZHOU ; Mou ZHOU ; Xiaoyu ZHOU ; Xuelian ZHOU ; Yuan ZHOU ; Zheng ZHOU ; Zuhuang ZHOU ; Haiyan ZHU ; Peiyuan ZHU ; Changju ZHU ; Lili ZHU ; Zhengguo WANG ; Jianxin JIANG ; Deqing WANG ; Jiongcai LAN ; Quanli WANG ; Yang YU ; Lianyang ZHANG ; Aiqing WEN
Chinese Journal of Trauma 2024;40(10):865-881
Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.
3.Baimai Ointment relieves chronic pain induced by chronic compression of dorsal root ganglion in rats by regulating neuroactive ligand-receptor interaction and HIF-1 signaling pathway.
Fang-Ting ZHOU ; Ying ZONG ; Wu-Qiong HOU ; Sen-Sen LI ; Fei YANG ; Li-Ting XU ; Xia MAO ; Yu-Dong LIU ; Xiao-Hui SU ; Hong-Ye WAN ; Jing-Feng OUYANG ; Qiu-Yan GUO ; Wei-Jie LI ; Zhen WANG ; Chao WANG ; Na LIN
China Journal of Chinese Materia Medica 2023;48(23):6457-6474
The Baimai Ointment with the effect of relaxing sinew and activating collaterals demonstrates a definite effect on Baimai disease with pain, spasm, stiffness and other symptoms, while the pharmacodynamic characteristics and mechanism of this agent remain unclear. In this study, a rat model of chronic compression of L4 dorsal root ganglion(CCD) was established by lumbar disc herniation, and the efficacy and mechanism of Baimai Ointment in the treatment of CCD were preliminarily explored by behavioral tests, side effect evaluation, network analysis, antagonist and molecular biology verification. The pharmacodynamic experiment indicated that Baimai Ointment significantly improved the pain thresholds(mechanical pain, thermal pain, and cold pain) and gait behavior of CCD model rats without causing tolerance or obvious toxic and side effects. Baimai Ointment inhibited the second-phase nociceptive response of mice in the formalin test, increased the hot plate threshold of normal mice, and down-regulated the expression of inflammatory cytokines in the spinal cord. Network analysis showed that Baimai Ointment had synergistic effect in the treatment of CCD and was related to descending inhibition/facilitation system and neuroinflammation. Furthermore, behavioral tests, Western blot, and immunofluorescence assay revealed that the pain-relieving effect of Baimai Ointment on CCD may be related to the regulation of the interaction between neuroactive ligand and receptors(neuroligands) such as CHRNA7, ADRA2A, and ADRB2, and the down-regulation of the expression of NOS2/pERK/PI3K, the core regulatory element of HIF-1 signaling pathway in spinal microglia. The findings preliminarily reveal the mechanism of relaxing sinew and activating collaterals of Baimai Ointment in the treatment of Baimai disease, providing a reference for the rational drug use and further research of this agent.
Rats
;
Mice
;
Animals
;
Chronic Pain/metabolism*
;
Rats, Sprague-Dawley
;
Ganglia, Spinal/metabolism*
;
Ligands
;
Signal Transduction
;
Hyperalgesia/metabolism*
;
Drugs, Chinese Herbal
4.Correlation between triglyceride-glucose index and high on-treatment platelet reactivity during clopidogrel treatment in patients with ischemic stroke
Haoxuan CHEN ; Li YANG ; Zhenzhen LOU ; Yibo ZHAN ; Huiying OUYANG ; Guixian CHEN ; Changlin ZHANG ; Hui MAO ; Xiaojun LI ; Zhiping HUANG ; Zequan ZHENG ; Haoyou XU ; Longlong WEN ; Min ZHAO ; Yuanqi ZHAO
International Journal of Cerebrovascular Diseases 2023;31(4):253-258
Objective:To investigate the correlation between triglyceride-glucose (TyG) index and high on-treatment platelet reactivity (HTPR) during clopidogrel treatment in patients with ischemic stroke.Methods:Patients with ischemic stroke who received maintenance dose of clopidogrel (75 mg/d) in the Department of Neurology, Guangdong Provincial Hospital of Chinese Medicine from January 2017 to March 2021 were retrospectively included. The highest quartile (Q4) of the TyG index was defined as insulin resistance. Platelet reactivity was assessed by thromboelastogram and clopidogrel HTPR was defined as the clot strength induced by adenosine diphosphate (MA ADP) >47 mm. Multivariate regression model was used to analyze the independent correlation between TyG index and platelet reactivity. Results:A total of 83 patients were included. The TyG index showed a linear correlation with MA ADP. The patients were divided into 4 groups according to the quartile of TyG index. The incidence of clopidogrel HTPR increased significantly with the increase of the quartile of the TyG index ( Ptrend=0.017). Multivariate analysis showed that there was a significant independent correlation between insulin resistance and clopidogrel HTPR (odds ratio 4.597, 95% confidence interval 1.285-16.446; P=0.019). Conclusions:In patients with ischemic stroke treated with clopidogrel, the incidence of clopidogrel HTPR gradually increases with the increase of the quartile of the TyG index. The insulin resistance assessed by the TyG index is independently associated with clopidogrel HTPR.
5.Research progress on the relationship between periodontitis and chronic obstructive pulmonary disease
Yan MAO ; Yingqiu HU ; Aibing LI ; Ming OUYANG
Chinese Journal of General Practitioners 2023;22(12):1315-1319
Periodontitis is a chronic periodontal disease with a high incidence, and chronic obstructive pulmonary disease (COPD) is considered to be a chronic airway inflammatory disease. In recent years, many studies have observed that there is a potential relationship between periodontitis and COPD. The periodontal condition of patients with COPD is relatively poor, and the composition of their oral microbiome is different from that of healthy people. The inflammation “spillage”and hypoxia may induce the occurrence and development of periodontal disease. At the same time, the risk of COPD in periodontitis patients may be related to the inhalation of periodontal pathogens and inflammatory factors. Regular periodontal sequence therapy can reduce the risk of acute exacerbation of the disease to a certain extent. Since periodontitis and COPD are both chronic progressive diseases characterized by chronic inflammation and accompanied by proteolytic destruction of connective tissue, they may share a common pathophysiological process and may be intrinsically linked. This article reviews the latest research progress on the relationship between chronic periodontitis and COPD, and possible interaction mechanism, in order to provide insight for further study on the interaction between the two conditions.
6.A comprehensive update: gastrointestinal microflora, gastric cancer and gastric premalignant condition, and intervention by traditional Chinese medicine.
Yuting LU ; Huayi LIU ; Kuo YANG ; Yijia MAO ; Lingkai MENG ; Liu YANG ; Guangze OUYANG ; Wenjie LIU
Journal of Zhejiang University. Science. B 2022;23(1):1-18
With the recent upsurge of studies in the field of microbiology, we have learned more about the complexity of the gastrointestinal microecosystem. More than 30 genera and 1000 species of gastrointestinal microflora have been found. The structure of the normal microflora is relatively stable, and is in an interdependent and restricted dynamic equilibrium with the body. In recent years, studies have shown that there is a potential relationship between gastrointestinal microflora imbalance and gastric cancer (GC) and precancerous lesions. So, restoring the balance of gastrointestinal microflora is of great significance. Moreover, intervention in gastric premalignant condition (GPC), also known as precancerous lesion of gastric cancer (PLGC), has been the focus of current clinical studies. The holistic view of traditional Chinese medicine (TCM) is consistent with the microecology concept, and oral TCM can play a two-way regulatory role directly with the microflora in the digestive tract, restoring the homeostasis of gastrointestinal microflora to prevent canceration. However, large gaps in knowledge remain to be addressed. This review aims to provide new ideas and a reference for clinical practice.
Drugs, Chinese Herbal/therapeutic use*
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Gastrointestinal Microbiome
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Humans
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Medicine, Chinese Traditional
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Precancerous Conditions/pathology*
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Stomach Neoplasms/pathology*
7.Therapeutic potential of traditional Chinese medicine for vascular endothelial growth factor.
Yijia MAO ; Lingkai MENG ; Huayi LIU ; Yuting LU ; Kuo YANG ; Guangze OUYANG ; Yanran BAN ; Shuang CHEN
Journal of Zhejiang University. Science. B 2022;23(5):353-364
Vascular endothelial growth factor (VEGF) is the main regulator of physiological angiogenesis during embryonic development, bone growth, and reproductive function, and it also participates in a series of pathological changes. Traditional Chinese medicine (TCM), with a history of more than 2000 years, has been widely used in clinical practice, while the exploration of its mechanisms has only begun. This review summarizes the research of recent years on the influence of TCM on VEGF. It is found that many Chinese medicines and recipes have a regulatory effect on VEGF, indicating that Chinese medicine has broad prospects as a complementary and alternative therapy, providing new treatment ideas for clinical applications and the theoretical basis for research on the mechanisms of TCM.
Drugs, Chinese Herbal/therapeutic use*
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Medicine, Chinese Traditional
;
Vascular Endothelial Growth Factor A
8.Effect of Sanjie Xiaoliu Recipe on epithelial mesenchymal transformation of transplanted tumor in breast cancer mice
Dongyan HE ; Yuhua WU ; Mao CHEN ; Zhe PENG ; Yushan LIAO ; Zhenwen OUYANG ; Weijia HU
Journal of Chinese Physician 2022;24(7):996-1001
Objective:To study the effect of Sanjie Xiaoliu Recipe on transplanted tumors in breast cancer mice through in vivo experiments, in order to explore the efficacy and mechanism of Sanjie Xiaoliu Recipe on breast cancer patients. Methods:45 BaL B/c female mice were selected to establish the transplanted tumor model of breast cancer. All the transplanted tumor models of breast cancer mice were randomly divided into five groups: the control group (intragastric administration of normal saline), the low, medium and high dose group of Sanjie Xiaoliu Recipe (intragastric administration of different doses of Sanjie Xiaoliu Decoction), and the paclitaxel group (intraperitoneal injection of paclitaxel). After 24 days of continuous administration, the diet and activities of mice were observed; the body weight, weight and volume changes of transplanted tumor mice were recorded, and the tumor inhibition rate was calculated. Western blot was used to detect the expression of epithelial mesenchymal transformation related proteins (E-cadherin, N-cadherin, Vimentin) in the transplanted tumor tissues of mice in each group.Results:(1) The food intake and activity status of mice treated with Sanjie Xiaoliu Recipe were less affected by the transplanted tumor of breast cancer. (2) The volume and weight of transplanted tumor in the treat groups were smaller than those in the control group (all P<0.01), and the volume of transplanted tumor in the middle dose group of Sanjie Xiaoliu Recipe was smaller than that in the low dose group ( P<0.05). The tumor inhibition rates among the treatment groups were: Sanjie Xiaoliu Recipe medium dose group 52.4%, paclitaxel group 40.3%, Sanjie Xiaoliu Recipe low dose group 39.5%, Sanjie Xiaoliu Recipe high dose group 34.1%. (3) The results of Western blot showed that the expression level of E-cadherin in the transplanted tumor tissue of the treat groups was higher than that in the control group, and the expression levels of N-cadherin and Vimentin were lower than that in the control group, with statistically significant difference (all P<0.05). Conclusions:The Sanjie Xiaoliu Recipe can improve the weakness and reduced consumption of breast cancer mice, which can inhibit the tumor mass growth in mice to a certain extent. Its mechanism may be that Sanjie Xiaoliu Recipe can inhibit the epithelial mesenchymal transformation of breast cancer and the invasion and metastasis of breast cancer.
9.Research progress in establishment of N-methyl-N'-nitro-N-nitroso-guanidine-induced rat model of Precancerous lesion of gastric cancer.
Yu-Ting LU ; Hua-Yi LIU ; Jia-Ju SHANG ; Yi-Jia MAO ; Guang-Ze OUYANG ; Liu YANG
China Journal of Chinese Materia Medica 2021;46(16):4089-4095
Gastric cancer(GC), one of the most common malignancies worldwide, seriously threatens human health due to its high morbidity and mortality. Precancerous lesion of gastric cancer(PLGC) is a critical stage for preventing the occurrence of gastric cancer, and PLGC therapy has frequently been investigated in clinical research. Exploring the proper animal modeling methods is necessary since animal experiment acts as the main avenue of the research on GC treatment. At present, N-methyl-N'-nitro-N-nitroso-guanidine(MNNG) serves as a common chemical inducer for the rat model of GC and PLGC. In this study, MNNG-based methods for modeling PLGC rats in related papers were summarized, and the applications and effects of these methods were demonstrated by examples. Additionally, the advantages, disadvantages, and precautions of various modeling methods were briefly reviewed, and the experience of this research group in exploring modeling methods was shared. This study is expected to provide a reference for the establishment of MNNG-induced PLGC animal model, and a model support for the following studies on PLGC.
Animals
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Gastric Mucosa
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Methylnitronitrosoguanidine/toxicity*
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Precancerous Conditions/chemically induced*
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Rats
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Stomach Neoplasms/drug therapy*
10.Outcomes and the role of adjuvant therapy of limited stage small cell lung cancer undergoing surgical treatment
Jing YU ; Wen OUYANG ; Zhao HUANG ; Gang CHEN ; Yan ZHOU ; Yanling MAO ; Junhong ZHANG ; Conghua XIE
Chinese Journal of Oncology 2020;42(4):336-339
Objective:To investigate the outcomes of limited stage small cell lung cancer (L-SCLC) undergoing surgical therapy and to explore the value of adjuvant therapy for those patients.Methods:A retrospective analysis was initialed for the L-SCLC patients who underwent the surgical treatment in the Zhongnan Hospital of Wuhan University from January 2012 to December 2018. The median disease-free survival (DFS) and overall survival (OS) were calculated by Kaplan-Meier method. Cox regression was used to explore the prognostic factors.Results:A total of 44 patients were included in our study. The median DFS was 25 months, 1- and 2-year DFS rate were 70.2% and 51.9%, respectively. The median OS was 41 months, 1- and 2- year OS rate were 88.4% and 69.9%, respectively. Multivariate analysis showed male ( RR=6.56, P=0.03), T3-4 ( RR=6.23, P=0.01), pathological lymph node metastasis ( RR=6.52, P=0.03) and adjuvant radiotherapy ( RR=0.13, P=0.002) were associated with disease relapse significantly. Moreover, pathological lymph node metastasis ( RR=3.62, P=0.01) coupled with sufficient adjuvant chemotherapy (≥4 cycles) ( RR=0.12, P=0.01) were independent prognostic factors of OS. Conclusions:Surgical therapy may be an alternative primary treatment for L-SCLC. Additional adjuvant radiotherapy can reduce the risk of recurrence. Giving sufficient course of adjuvant chemotherapy can improve OS.

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