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Establishment of a cholangiocarcinoma risk evaluation model based on mucin expression levels

World Journal of Gastrointestinal Oncology 2024年第4期16卷 1344-1360页

作者： Chun-Yuan Yang Li-Mei Guo Yang Li Guang-Xi Wang Xiao-Wei Tang Qiu-Lu Zhang Ling-Fu Zhang Jian-Yuan Luo department of pathology Institute of Systems BiomedicineSchool of Basic Medical Sciences Peking UniversityPeking University Third HospitalPeking University Health Science CenterBeijing 100191China department of General Surgery Peking University Third HospitalBeijing 100191China department of Medical Genetics Department of Biochemistry and BiophysicsSchool of Basic Medical Sciences Peking UniversityPeking University Health Science CenterBeijing 100191China

BACKGROUND Cholangiocarcinoma(CCA)is a highly malignant cancer,characterized by frequent mucin ***1 has been identified as a critical oncogene in the progression of ***,the comprehensive understanding of how the mucin family influences CCA progression and prognosis is still *** To investigate the functions of mucins on the progression of CCA and to establish a risk evaluation formula for stratifying CCA *** Single-cell RNA sequencing data from 14 CCA samples were employed for elucidating the roles of mucins,complemented by bioinformatic ***-quent validations were conducted through spatial transcriptomics and *** construction of a risk evaluation model utilized the least absolute shrinkage and selection operator regression algorithm,which was further confirmed by independent cohorts and diverse data *** CCA tumor cells with elevated levels of MUC1 and MUC4 showed activated nucleotide metabolic pathways and increased ***5AC-high cells were found to promote CCA progression through WNT ***5B-high cells exhibited robust cellular oxidation activities,leading to resistance against antitumoral ***13-high cells were observed to secret chemokines,recruiting and transforming macrophages into the M2-polarized state,thereby suppressing antitumor ***16-high cells were found to promote tumor progression through interleukin-1/nuclear factor kappa-light-chain-enhancer of activated B cells signaling upon interaction with *** the expression levels of these mucins,a risk factor evaluation formula for CCA was developed and validated across multiple *** samples with higher risk factors exhibited stronger metastatic potential,chemotherapy resistance,and poorer *** Our study elucidates the functional mechanisms through which mucins contribute to CCA development,and provides tools for risk stratification in CCA.

关键词： Mucin Cholangiocarcinoma Single-cell RNA sequencing Spatial transcriptomics Prognosis

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Hepatocellular carcinoma presenting as an extrahepatic mass:A case report and review of literature

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 2241-2252页

作者： Wei Kelly Wu Krutika Patel Chandrasekhar Padmanabhan Kamran Idrees department of Surgery Vanderbilt University Medical CenterNashvilleTN 37232United States department of pathology Microbiology and ImmunologyVanderbilt University Medical CenterNashvilleTN 37232United States Division of Surgical Oncology and Endocrine Surgery Department of SurgeryVanderbilt University Medical CenterNashvilleTN 37232United States

BACKGROUND Hepatocellular carcinoma(HCC)is a primary liver tumor generally diagnosed based on radiographic *** disease is typically associated with increased tumor diameter,multifocality,and vascular *** report a case of a patient who presented with extrahepatic HCC metastasis to a portocaval lymph node with occult hepatic primary on computed tomography(CT).We review the literature for cases of extrahepatic HCC presentation without known hepatic lesions and discuss strategies to differentiate between metastatic and ectopic *** SUMMARY A 67-year-old male with remotely treated hepatis C was referred for evaluation of an enlarging portocaval,mixed cystic-solid *** CT evaluations demonstrated steatosis,but no cirrhosis or liver *** ultrasound demonstrated a normal-appearing pancreas,biliary tree,and *** needle aspiration yielded atypical *** differential diagnosis included duodenal or pancreatic cyst,lymphoproliferative cyst,stromal or mesenchymal lesions,nodal involvement from gastrointestinal or hematologic malignancy,or duodenal gastrointestinal stromal *** review by a multidisciplinary tumor board,the patient underwent open surgical resection of a 5.2 cm×5.5 cm retroperitoneal mass with pathology consistent with moderately-differentiated *** resonance imaging(MRI)subsequently demonstrated a 1.2 cm segment VIII hepatic lesion with late arterial enhancement,fatty sparing,and intrinsic T1 *** fetoprotein was 23.3 ng/*** patient was diagnosed with HCC with portocaval nodal ***:We surveyed the literature for HCC presenting as extrahepatic masses without history of concurrent or prior intrahepatic *** identified 18 cases of extrahepatic HCC ultimately found to represent metastatic lesions,and 30 cases of extrahepatic HCC found to be primary,ectopic *** Hepatocellular carcinoma can seldomly present with extrahepatic metastasis in the setting of

关键词： Extrahepatic Metastasis Portocaval Lymph node Case report

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Diagnosis and treatment of biliary mucinous cystic neoplasms: A single-center experience

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Hepatobiliary & Pancreatic Diseases International 2024年第5期23卷 495-501页

作者： Jun-Jun Jia Ya-Fen Cheng Mei-Bao Feng Li Liu Ming-Qi Shuai Xiao-Dong Shen Xiao-Feng Tang Shu-Sen Zheng Division of Hepatobiliary and Pancreatic Surgery Department of Surgerythe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China department of International Healthcare Center the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China department of pathology the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China department of Library the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China

Background: Biliary mucinous cystic neoplasms(BMCNs) are rare hepatobiliary cystic tumors, which can be divided into noninvasive and invasive types. This study aimed to investigate the diagnosis, treatment, and prognosis of BMCNs in a large single center. Methods: We analyzed 49 patients with BMCNs confirmed by postoperative pathology at the First Afflliated Hospital, Zhejiang university School of Medicine between January 2007 and December 2021. Results: Among the 49 patients, 37 were female(75.5%), and the average age was 57.04 years. Common symptoms included abdominal discomfort, jaundice and fever, while 22 patients(44.9%) had no symptoms. Serum carbohydrate antigen(CA) 19-9 and CA125 concentrations were elevated in 34.8% and 19.6% of patients, respectively. Forty-eight patients had tumors in the intrahepatic bile ducts and only one had a tumor in the extrahepatic bile duct. Forty-eight patients with noninvasive intrahepatic BMCNs were further analyzed in terms of pathological features: 34(70.8%) had low-grade intraepithelial neoplasms(LGINs), and 14(29.2%) had high-grade intraepithelial neoplasms(HGINs). The potential immunohistochemical markers of BMCNs were cytokeratin(CK) 19, CK7, estrogen receptor and progesterone receptor. Follow-up data for 37 patients with intrahepatic BMCNs were obtained. The median overall survival(OS) of BMCNs was not reached. The longest survival time was 137 *** 5-and 10-year OS rates were 100% and 85.4%, respectively. The 5-and 10-year recurrence-free survival(RFS) rates were 93.9% and 80.2%, respectively. Conclusions: BMCNs are rare cystic neoplasms that commonly occur in middle-aged females. BMCNs can only be diagnosed and classified by postoperative pathology, as there are no specific clinical presentations, serological indicators or imaging modalities for preoperative diagnosis. Complete surgical resection is necessary for BMCNs, and the postoperative prognosis is favorable.

关键词： Biliary mucinous cystic neoplasms Low-grade intraepithelial neoplasms High-grade intraepithelial neoplasms Overall survival Recurrence-free survival

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COVID-19 vaccination produces exercise-responsive SARS-CoV-2 specific T-cells regardless of infection history

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Journal of Sport and Health Science 2024年第1期13卷 99-107页

作者： Kyle A.Smith Tiffany M.Zúñiga Forrest L.Baker Helena Batatinha Charles R.Pedlar Shane C.Burgess Michael P.Gustafson Emmanuel Katsanis Richard J.Simpson School of Nutritional Sciences and Wellness The University of ArizonaTucsonAZ 85721USA department of Pediatrics The University of ArizonaTucsonAZ 85724USA Faculty of Sport Allied Health and Performance ScienceSt.Mary's UniversityTwickenham TW14SXUK Institute of Sport Exercise and Health University College LondonLondon WC1E 7HUUK department of Animal and Comparative Biomedical Sciences The University of ArizonaTucsonAZ 85721USA The university of Arizona Cancer Center The University of ArizonaTucsonAZ 85719USA Laboratory Medicine and pathology Mayo Clinic ArizonaPhoenixAZ 85054USA department of Immunobiology The University of ArizonaTucsonAZ 85724USA department of Medicine The University of ArizonaTucsonAZ 85724USA department of pathology The University of ArizonaTucsonAZ 85724USA

Background:The mobilization and redistribution of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)specific T-cells and neutralizing antibodies(nAbs)during exercise is purported to increase immune surveillance and protect against severe coronavirus disease 2019(COVID-19).We sought to determine if COVID-19 vaccination would elicit exercise-responsive SARS-CoV-2 T-cells and transiently alter nAb ***:Eighteen healthy participants completed a 20-min bout of graded cycling exercise before and/or after receiving a COVID-19 *** major leukocyte subtypes were enumerated before,during,and after exercise by flow cytometry,and immune responses to SARS-CoV-2 were determined using whole blood peptide stimulation assays,T-cell receptor(TCR)-βsequencing,and SARS-CoV-2 nAb ***:COVID-19 vaccination had no effect on the mobilization or egress of major leukocyte subsets in response to intensity-controlled graded ***,non-infected participants had a significantly reduced mobilization of CD4+and CD8+naive T-cells,as well as CD4+central memory T-cells,after vaccination(synthetic immunity group);this was not seen after vaccination in those with prior SARS-CoV-2 infection(hybrid immunity group).Acute exercise after vaccination robustly mobilized SARS-CoV-2 specific T-cells to blood in an intensity-dependent *** groups mobilized T-cells that reacted to spike protein;however,only the hybrid immunity group mobilized T-cells that reacted to membrane and nucleocapsid *** increased significantly during exercise only in the hybrid immunity ***:These data indicate that acute exercise mobilizes SARS-CoV-2 specific T-cells that recognize spike protein and increases the redistribution of nAbs in individuals with hybrid immunity.

关键词： Anti-viral COVID-19 Exercise immunology SARS-CoV-2 T-Cells Vaccine

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Acute upper gastrointestinal bleeding due to portal hypertension in a patient with primary myelofibrosis:A case report

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World Journal of Clinical Cases 2024年第15期12卷 2621-2626页

作者： Yu Chen Bing-Bing Kong He Yin Hao Liu Sheng Wu Ting Xu department of Emergency Beijing Tsinghua Changgung HospitalSchool of Clinical MedicineTsinghua UniversityBeijing 102218China department of pathology Beijing Tsinghua Changgung HospitalSchool of Clinical MedicineTsinghua UniversityBeijing 102218China

BACKGROUND Acute upper gastrointestinal bleeding is a common medical emergency that has a 10%hospital mortality *** to the etiology,this disease can be divided into acute varicose veins and nonvaricose *** from esophageal varices is a life-threatening complication of portal *** hypertension is a clinical syndrome defined as a portal venous pressure that exceeds 10 *** is the most common cause of portal hypertension,and thrombosis of the portal system not associated with liver cirrhosis is the second most common cause of portal hypertension in the Western *** myeloproliferative disorders are the main cause of portal venous thrombosis,and somatic mutations in the Janus kinase 2 gene(JAK2 V617F)can be found in approximately 90% of polycythemia vera,50% of essential thrombocyrosis and 50% of primary *** SUMMARY We present a rare case of primary myelofibrosis with gastrointestinal bleeding as the primary manifestation that presented as portal-superior-splenic mesenteric vein *** blood tests revealed the presence of the JAK2 V617F *** marrow biopsy ultimately confirmed the diagnosis of myelofibrosis(MF-2 grade).CONCLUSION In patients with acute esophageal variceal bleeding due to portal hypertension and vein thrombosis without cirrhosis,the possibility of myeloproliferative neoplasms should be considered,and the JAK2 mutation test should be performed.

关键词： Acute esophageal variceal bleeding Portal hypertension Myelofibrosis JAK2 V617F mutation Case report

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Trametinib boosts palbociclib’s efficacy in breast cancer via autophagy inhibition

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Oncology Research 2024年第7期32卷 1197-1207页

作者： ANGUO WU JIAO YAN TING SU CHI FENG XIN LONG YIRU PAN RUPEI YE TIAN XIA HANAN LONG JIANMING WU XIULI XIAO Sichuan Key Medical Laboratory of New Drug Discovery and Druggability Evaluation Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia MedicaKey Laboratory of Medical Electrophysiology of Ministry of EducationSchool of PharmacySouthwest Medical UniversityLuzhou646000China The department of pathology The Affiliated Hospital of Southwest Medical UniversityLuzhou646000China The department of pathology Mianyang Central HospitalSchool of MedicineUniversity of Electronic Science and Technology of ChinaMianyang621000China The department of pathology Yongchuan Hospital of Chongqing Medical UniversityChongqing402160China School of Basic Medical Sciences Southwest Medical UniversityLuzhou646000China School of Clinical Medical Sciences Southwest Medical UniversityLuzhou646000China

Breast cancer,a predominant global health issue,requires ongoing exploration of new therapeutic ***(PAL),a well-known cyclin-dependent kinase(CDK)inhibitor,plays a critical role in breast cancer *** its efﬁcacy is recognized,the interplay between PAL and cellular autophagy,particularly in the context of the RAF/MEK/ERK signaling pathway,remains insufﬁciently *** study investigates PAL’s inhibitory effects on breast cancer using both in vitro(MCF7 and MDA-MB-468 cells)and in vivo(tumor-bearing nude mice)*** at elucidating the impact of PAL on autophagic processes and exploring the potential of combining it with trametinib(TRA),an MEK inhibitor,our research seeks to address the challenge of PAL-induced drug ***ﬁndings reveal that PAL signiﬁcantly decreases the viability of MCF7 and MDA-MB-468 cells and reduces tumor size in mice while showing minimal cytotoxicity in MCF10A ***,PAL also induces protective autophagy,potentially leading to drug resistance via the RAF/MEK/ERK pathway *** TRA effectively neutralized this autophagy,enhancing PAL’s anti-tumor efﬁcacy.A combination of PAL and TRA synergistically reduced cell viability and proliferation,and in vivo studies showed notable tumor size *** conclusion,the PAL and TRA combination emerges as a promising strategy for overcoming PAL-induced resistance,offering a new horizon in breast cancer treatment.

关键词： Palbociclib Trametinib Protective autophagy RAF/MEK/ERK MCF7 MDA-MB-468

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Comprehensive analysis of the gut microbiome and posttranslational modifications elucidates the route involved in microbiota-host interactions

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Zoological Research 2024年第1期45卷 95-107页

作者： Hai-Yang Wang Lan-Xiang Liu Xue-Yi Chen Yang-Dong Zhang Wen-Xia Li Wen-Wen Li Lian Wang Xiao-Long Mo Hong Wei Ping Ji Peng Xie NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China College of Stomatology and Affiliated Stomatological Hospital of Chongqing Medical university Chongqing 401147China Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences Chongqing 401147China department of Neurology Yongchuan Hospital of Chongqing Medical UniversityChongqing 402160China department of pathology Faculty of Basic MedicineChongqing Medical UniversityChongqing 400016China department of Neurology First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Yu-Yue pathology Scientific Research Center Chongqing 401329China

The gut microbiome interacts with the host to maintain body homeostasis,with gut microbial dysbiosis implicated in many ***,the underlying mechanisms of gut microbe regulation of host behavior and brain functions remain *** study aimed to elucidate the influence of gut microbiota on brain functions via post-translational modification mechanisms in the presence or absence of bacteria without any *** conducted succinylome analysis of hippocampal proteins in germ-free(GF)and specific pathogen-free(SPF)mice and metagenomic analysis of feces from SPF *** results were integrated with previously reported hippocampal acetylome and phosphorylome data from the same batch of *** bioinformatics analyses revealed 584 succinylation sites on 455 proteins,including 54 up-regulated succinylation sites on 91 proteins and 99 down-regulated sites on 51 proteins in the GF mice compared to the SPF *** constructed a panoramic map of gut microbiota-regulated succinylation,acetylation,and phosphorylation,and identified cross-talk and relative independence between the different types of post-translational modifications in modulating complicated intracellular *** correlation analysis indicated that 13 taxa,predominantly belonging to the Bacteroidetes phylum,were correlated with the biological functions of post-translational *** correlations between these taxa and succinylation and negative correlations between these taxa and acetylation were identified in the modulation of intracellular *** study highlights the hippocampal physiological changes induced by the absence of gut microbiota,and proteomic quantification of succinylation,phosphorylation,and acetylation,contributing to our understanding of the role of the gut microbiome in brain function and behavioral phenotypes.

关键词： Gut microbiota Hippocampal protein Post-translational modifications Succinylation Acetylation Phosphorylation

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Progress of vegetation modelling and future research prospects

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Science China Earth Sciences 2024年第9期67卷 2718-2738页

作者： Siqi LI Xu ZHANG Zhengyao LU Jian NI Jianhua LU State Key Laboratory of Tibetan Plateau Earth System Resources and Environment(TPESRE)Institute of Tibetan Plateau ResearchChinese Academy of SciencesBeijing 100101China College of Resources and Environment University of Chinese Academy of SciencesBeijing 100049China British Antarctic Survey Cambridge CB30ETUnited Kingdom department of Physical Geography and Ecosystem Science Lund UniversityLund 22362Sweden College of Life Sciences Zhejiang Normal UniversityJinhua 321004China School of Atmospheric Sciences Sun Yat-sen University and Southern Marine Science and Engineering Guangdong Laboratory(Zhuhai)Zhuhai 519082China

Terrestrial vegetation is a crucial component of the Earth system,and its changes not only represent one of the most distinct aspects of climate change but also exert significant feedback within the climate system by exchanging energy,moisture,and carbon *** quantitatively and mechanistically study climate-vegetation feedback,numerical vegetation models have been developed on the theory of ecophysiological constraints on plant functional *** models eventually can simulate vegetation distribution and succession across different spatial and temporal scales,and associated terrestrial carbon cycle processes by categorizing vegetation into biomes according different plant functional types and their associated environmental *** we review the developing history of vegetation models and provide recent advances and future *** 21st century,static vegetation models,as developed statistical models,can only simulate equilibrated characteristics of vegetation *** last several decades,Dynamic Global Vegetation Models(DGVMs)have been developed to simulate instantaneous responses of vegetation to climate change and associated dynamics,and can be coupled with Earth system models to investigate interactions among atmosphere,ocean,and *** are also widely applied to investigate the dynamics accounting for changes in the geographic distribution patterns of land surface vegetation at different spatial and temporal scales and to assess the impacts of terrestrial carbon and water fluxes and land use *** suggest that future vegetation modeling could integrate with machine learning,and explore vegetation transient response and feedback as well as impacts of process hierarchies and human activities on climate and ecosystem.

关键词： Vegetation models DGVMs Ecosystems Plant functional types Plant functional traits

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Mechanical sensor PDLIM5 promotes the osteogenesis of human adipose-derived stem cells through microfilament alterations

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Genes & Diseases 2024年第3期11卷 136-139页

作者： Yuchao Yang Shutong Wu Rongmei Qu Congrong Wang Jinyang Wang Asmat Ullah Khan You Pan Wenqing Liu Jinhui Zhu Muhammad Akram Khan Chujiang Xu Jingxing Dai Jun Ouyang Guangdong Provincial Key Laboratory of Medical Biomechanics&National Key Discipline of Human Anatomy Schoolof BasicMedical SciencesSouthern Medical UniversityGuangzhouGuangdong 510515China department of Laboratory Medicine Nanfang Hospital of Southern Medical UniversityGuangzhouGuangdong 510515China department of pathology Guangdong Provincial People's HospitalGuangdong Academy of Medical SciencesGuangzhouGuangdong 510080China department of Breast Surgery Guangxi Medical University Cancer HospitalNanningGuangxi 530000China department of Veterinary pathology Faculty of Veterinary and Animal SciencesPMAS Arid Agriculture UniversityRawalpindi 46300Pakistan department of Orthopedics TCM-Integrated HospitalSouthern Medical UniversityGuangzhouGuangdong 510000China

Bone regeneration is a multifaceted,abstract,and wellcoordinated physiological progression of bone formation that participates in continuous regeneration and remodeling throughout ***,when it comes to complex clinical situations requiring extensive bone regeneration,such as massive bone defects caused by injuries,infection,or tumor removal,traditional methods do not often yield good treatment strategies or protocols due to their limitations.

关键词： alterations injuries massive

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Aldo-keto reductases:Role in cancer development and theranostics

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Oncology Research 2024年第8期32卷 1287-1308页

作者： SIDDAVARAM NAGINI PRATHAP REDDY KALLAMADI KRANTHI KIRAN KISHORE TANAGALA GEEREDDY BHANUPRAKASH REDDY World Neem Organization Mumbai400101India department of Biochemistry ICMR-National Institute of NutritionHyderabad500007India department of pathology and Cell Biology Columbia University Irving Medical CenterNew York10032USA

Aldo-keto reductases(AKRs)are a superfamily of enzymes that play crucial roles in various cellular processes,including the metabolism of xenobiotics,steroids,and carbohydrates.A growing body of evidence has unveiled the involvement of AKRs in the development and progression of various *** are aberrantly expressed in a wide range of malignant *** expression of AKRs enables the acquisition of hallmark traits of cancer by activating oncogenic signaling pathways and contributing to *** have emerged as promising oncotherapeutic targets given their pivotal role in cancer development and *** of aldose reductase(AR),either alone or in combination with chemotherapeutic drugs,has evolved as a pragmatic therapeutic option for *** classes of synthetic aldo-keto reductase(AKR)inhibitors have been developed as potential anticancer agents,some of which have shown promise in clinical *** AKR inhibitors from natural sources also exhibit anticancer *** molecule inhibitors targeting speciﬁc AKR isoforms have shown promise in preclinical *** inhibitors disrupt the activation of oncogenic signaling by modulating transcription factors and kinases and sensitizing cancer cells to *** this review,we discuss the physiological functions of human AKRs,the aberrant expression of AKRs in malignancies,the involvement of AKRs in the acquisition of cancer hallmarks,and the role of AKRs in oncogenic signaling,and drug ***,the potential of aldose reductase inhibitors(ARIs)as anticancer drugs is summarized.

关键词： Aldo-keto reductases(AKRs) Aldo-keto reductase(AKR)inhibitors Cancer Drug-resistance Xenobiotics

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