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A genetic variant study of bortezomib-induced peripheral neuropathy in Chinese multiple myeloma patients

oncology Research 2024年第5期32卷 955-963页

作者： YAN ZHANG HEYANG ZHANG JING WANG XIN WEI YI QU FENG XU LIJUN ZHANG Department of hematology The First Affiliated Hospital of China Medical UniversityShenyang110001China

Background:Bortezomib results in peripheral neuropathy(PN)in approximately 50%of patients,during multiple myeloma(MM)treatment,a complication known as Bortezomib-induced peripheral neuropathy(BIPN).The drug response varies among *** factor may play an important role in ***:A nextgeneration sequencing(NGS)panel containing 1659 targets from 233 genes was used to identify risk variants for developing BIPN in 204 MM patients who received bortezomib *** expression of MTHFR and ALDH1A1 in 62 peripheral blood samples was detected by real-time quantitative PCR(RT-qPCR).Serum homocysteine(Hcy)levels were detected in 40 samples by chemiluminescent microparticle immunoassay(CMIA).Results:Compared with the non-BIPN group(n=89),a total of 8 significantly associated single nucleotide polymorphisms(SNPs)were identified in the BIPN group(n=115):MTHFR(rs1801131,rs1801133,rs17421511),EPHX1(rs1051740),MME(rs2016848),ALDH1A1(rs6151031),HTR7(rs1935349)and CYP2A6(rs8192720).The mRNA expression level of MTHFR in newly diagnosed patients with peripheral neuritis after treatment(NP group)was lower than that of newly diagnosed patients without peripheral neuritis after treatment(NnP group)(1.70±0.77 vs.2.81±0.97,p=0.009).Serum Hcy levels were significantly higher in BIPN group than in non-BIPN group(11.66±1.79μmol/L vs.8.52±3.29μmol/L,p=0.016)and healthy controls(11.66±1.79μmol/L vs.8.55±2.13μmol/L,p≤0.001).Conclusion:CYP2A6,EPHX1,MTHFR,ALDH1A1,HTR7,MME and BIPN are linked in Chinese MM *** is more likely to occur in patients with lower MTHFR mRNA expression,which might result in higher serum Hcy levels.

关键词： Multiple Myeloma Peripheral neuropathy Bortezomib Bortezomib-induced peripheral neuropathy Next-generation sequencing MTHFR Serum Hcy

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Analysis of the role of dihydromyricetin derived from vine tea(Ampelopsis grossedentata)on multiple myeloma by activating STAT1/RIG-I axis

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oncology Research 2024年第8期32卷 1359-1368页

作者： WEI JIANG MEI ZHOU Department of hematology Shaoxing Shangyu People’s HospitalShaoxing312000China Department of hematology Zhuji People’s HospitalShaoxing311800China

Multiple myeloma(MM)is a plasma cell malignancy and remains incurable as it lacks effective curative approaches;thus,novel therapeutic strategies are desperately *** study aimed to explore the therapeutic role of dihydromyricetin(DHM)in MM and explore its *** MM and normal plasma samples,human MM cell lines,and normal plasma cells were used for in vitro *** counting kit-8(CCK-8),flow cytometry,and trans-well assays were performed for the assessment of cell viability,apoptosis,migration,and invasion,*** real-time polymerase chain reaction(qRT-PCR)was employed to assess the mRNA expression of signal transducer and activator of transcription 1(STAT1)and retinoic acid-inducible gene I(RIG-I).Western blotting was employed to assess E-cadherin,N-cadherin,signal transducer,STAT1,p-STAT1,and RIG-I protein expression.A tumor xenograft model was used for in vivo ***,dihydromyricetin(DHM)dose-dependently restrained viability,apoptosis,migration,and invasion,and facilitated apoptosis of U266 *** DHM treatment,the Ecadherin level was increased and the N-cadherin level was decreased in U266 and RPMI-8226 cells,suggesting the inhibitory effects of DHM on epithelial-mesenchymal transition(EMT)in ***,the levels of p-STAT1/STAT1 and RIG-I were down-regulated in ***,the STAT1 inhibitor fludarabine undid the suppressive effect of DMH on the malignant characteristics of U266 ***,DHM inhibited MM tumor growth and EMT,and activated STAT1/RIG-I pathway in ***,this study first revealed that DHM can restrain EMT and tumor growth in MM by activating STAT1/RIG-I signaling,which provides a novel drug for the treatment of MM.

关键词： Dihydromyricetin Multiple myeloma Epithelial-mesenchymal transition Tumor growth

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Reconstitution of double-negative T cells after cord blood transplantation and its predictive value for acute graft-versus-host disease

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Chinese Medical Journal 2024年第10期137卷 1207-1217页

作者： Tianzhong Pan Peng Ding Aijie Huang Baolin Tang Kaidi Song Guangyu Sun Yue Wu Shiying Yang Xingchi Chen Dongyao Wang Xiaoyu Zhu Department of hematology The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui 230001China Anhui Provincial Key Laboratory of Blood Research and Applications HefeiAnhui230001China Blood and Cell Therapy Institute Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui 230001China division of Life Sciences and Medicine University of Science and Technology of ChinaHefeiAnhui 230001China The First Affiliated Hospital of USTC Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui 230001China

Background:With an increasing number of patients with hematological malignancies being treated with umbilical cord blood transplantation(UCBT),the correlation between immune reconstitution(IR)after UCBT and graft-versus-host disease(GVHD)has been reported successively,but reports on double-negative T(DNT)cell reconstitution and its association with acute GVHD(aGVHD)after UCBT are ***:A population-based observational study was conducted among 131 patients with hematological malignancies who underwent single-unit UCBT as their first transplant at the Department of hematology,the First Affiliated Hospital of USTC,between August 2018 and June *** differences were compared between the patients with and without ***:The absolute number of DNT cells in the healthy Chinese population was 109(70-157)/μL,accounting for 5.82(3.98-8.19)%of *** cells showed delayed recovery and could not reach their normal levels even one year after ***,the absolute number and percentage of DNT cells were significantly higher in UCBT patients without aGVHD than in those with aGVHD within one year(F=4.684,P=0.039 and F=5.583,P=0.026,respectively).In addition,the number of DNT cells in the first month after transplantation decreased significantly with the degree of aGVHD increased,and faster DNT cell reconstitution in the first month after UCBT was an independent protective factor for aGVHD(HR=0.46,95%confidence interval[CI]:0.23-0.93;P=0.031).Conclusions:Compared to the number of DNT cells in Chinese healthy people,the reconstitution of DNT cells in adults with hematological malignancies after UCBT was *** addition,the faster reconstitution of DNT cells in the early stage after transplantation was associated with a lower incidence of aGVHD.

关键词： Umbilical cord blood transplantation Graft-versus-host disease Immune reconstitution Double negative T Hematological Malignancies Treg cell Breg cell

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Evidence-based expert consensus on clinical management of safety of Bruton’s tyrosine kinase inhibitors(2024)

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Chinese Journal of Cancer Research 2024年第3期36卷 240-256页

作者： Zaiwei Song Dan Jiang Lingling Yu Yixuan Chen Daobin Zhou Yue Li Depei Wu Lingli Zhang Liyan Miao Jun Ma Jun Zhu Hongmei Jing Rongsheng Zhao the Steering Committee,the Consensus Panel and the Evidence Synthesis Group Evidence-based Pharmacy Professional Committee of Chinese Pharmaceutical Association(CPA) Hospital Pharmacy Professional Committee of Chinese Pharmaceutical Association(CPA) division of Therapeutic Drug Monitoring of Chinese Pharmacological Society(CPS) Expert Committee on Lymphoma of Chinese Society of Clinical oncology(CSCO) Expert Committee on Leukemia of Chinese Society of Clinical oncology(CSCO) Society of Integrative Cardio-oncology of China Anti-Cancer Association(CACA) Chinese Society of hematology of Chinese Medical Association(CMA) Hospital Pharmacy Professional Committee of Cross-Straits Medicine Exchange Association(SMEA) Department of Pharmacy Peking University Third HospitalBeijing 100191China Institute for Drug Evaluation Peking University Health Science CenterBeijing 100191China Therapeutic Drug Monitoring and Clinical Toxicology Center Peking UniversityBeijing 100191China Department of Pharmacy Administration and Clinical Pharmacy School of Pharmaceutical SciencesPeking UniversityBeijing 100191China Department of hematology Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100005China Department of Cardiology the First Affiliated HospitalHarbin Medical UniversityHarbin 150001China Department of hematology the First Affiliated Hospital of Soochow UniversitySuzhou 215006China Department of Pharmacy Evidence-based Pharmacy CenterWest China Second HospitalSichuan UniversityChengdu 610041China Department of Pharmacy the First Affiliated Hospital of Soochow UniversitySuzhou 215006China Department of hematology and oncology Harbin Institute of Hematology and OncologyHarbin 150010China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of LymphomaPeking University Cancer Hospital&InstituteBeijing 100142China Department of hematology Peking University Third HospitalBeijing 100191China 不详

Bruton’s tyrosine kinase inhibitors(BTKis)have revolutionized the treatment of B-cell ***,safety issues related to the use of BTKis may hinder treatment continuity and further affect clinical efficacy.A comprehensive and systematic expert consensus from a pharmacological perspective is lacking for safety issues associated with BTKi treatment.A multidisciplinary consensus working group was established,comprising 35 members from the fields of hematology,cardiovascular disease,cardio-oncology,clinical pharmacy,and evidencebased *** evidence-based expert consensus was formulated using an evidence-based approach and the Delphi *** Joanna Briggs Institute Critical Appraisal(JBI)tool and Grading of Recommendations Assessment,Development,and Evaluation(GRADE)approach were used to rate the quality of evidence and grade the strength of recommendations,*** consensus provides practical recommendations for BTKis medication based on nine aspects within three domains,including the management of common adverse drug events such as bleeding,cardiovascular events,and hematological toxicity,as well as the management of drug-drug interactions and guidance for special *** multidisciplinary expert consensus could contribute to promoting a multi-dimensional,comprehensive and standardized management of BTKis.

关键词： Consensus BTK inhibitors safety adverse drug events drug-drug interactions

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Incidence and Survivability of Acute Lymphocytic Leukemia Patients in the United States: Analysis of SEER Data Set from 2000-2019

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Journal of Cancer Therapy 2024年第4期15卷 141-163页

作者： Ishan Ghosh Sudipto Mukherjee Department of Biology Rockhurst University Kansas City Missouri USA hematology and Medical oncology Cleveland Clinic Cleveland Ohio USA

The main goal of this research is to assess the impact of race, age at diagnosis, sex, and phenotype on the incidence and survivability of acute lymphocytic leukemia (ALL) among patients in the United States. By taking these factors into account, the study aims to explore how existing cancer registry data can aid in the early detection and effective treatment of ALL in patients. Our hypothesis was that statistically significant correlations exist between race, age at which patients were diagnosed, sex, and phenotype of the ALL patients, and their rate of incidence and survivability data were evaluated using SEER*Stat statistical software from National Cancer Institute. Analysis of the incidence data revealed that a higher prevalence of ALL was among the Caucasian population. The majority of ALL cases (59%) occurred in patients aged between 0 to 19 years at the time of diagnosis, and 56% of the affected individuals were male. The B-cell phenotype was predominantly associated with ALL cases (73%). When analyzing survivability data, it was observed that the 5-year survival rates slightly exceeded the 10-year survival rates for the respective demographics. Survivability rates of African Americans patients were the lowest compared to Caucasian, Asian, Pacific Islanders, Alaskan Native, Native Americans and others. Survivability rates progressively decreased for older patients. Moreover, this study investigated the typical treatment methods applied to ALL patients, mainly comprising chemotherapy, with occasional supplementation of radiation therapy as required. The study demonstrated the considerable efficacy of chemotherapy in enhancing patients’ chances of survival, while those who remained untreated faced a less favorable prognosis from the disease. Although a significant amount of data and information exists, this study can help doctors in the future by diagnosing patients with certain characteristics. It will further assist the health care professionals in screening

关键词： Acute Lymphocytic Leukemia Survivability Incidence Demography SEER Data Set

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RNF6 promotes chronic myelogenous leukemia cell proliferation and migration by stabilizing vimentin via multiple atypical ubiquitinations

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Genes & Diseases 2024年第1期11卷 87-90页

作者： Hongxia Zhang Yueya Zhong Yuanming He Yujia Xu Ying Ren Haixia Zhuang Tong Sun Zhigang Zhu Xinliang Mao Institute of Clinical Pharmacology Science and Technology Innovation CenterGuangzhou University of Chinese MedicineGuangzhouGuangdong 510403China Guangdong Provincial Key Laboratory of Protein Modification and Degradation School of Basic Medical SciencesGuangzhou Medical UniversityGuangzhouGuangdong 511436China Department of Pharmacology College of Pharmaceutical SciencesSoochow UniversitySuzhouJiangsu 215123China division of hematology&oncology Department of GeriatricsGuangzhou First People's HospitalCollege of MedicineSouth China University of TechnologyGuangzhouGuangdong 510180China

Chronic myelogenous leukemia(CML)is a malignancy from bone marrow myeloid stem cells mainly driven by the fusion gene *** addition to BCR-ABL,other genes including RNF6 are also dysregulated in CML cells.1 RNF6,a ubiquitin ligase of the RING family,promotes various cancer cell proliferation,chemoresistance,and tumor growth in vivo by targeting various proteins for ubiquitination and degradation,including SHP1,TLE3,FOXA1,and MAD1.^(2) However,its specific mechanism in CML is not known.

关键词： ubiquitin myelogenous leukemia

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COVID-19 mutations:An overview

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World Journal of Methodology 2024年第3期14卷 7-22页

作者： Malay Sarkar Irappa Madabhavi Department of Pulmonary Medicine Indira Gandhi Medical CollegeShimla 171001Himachal PradeshIndia Department of Medical and Pediatric oncology and hematology J N Medical Collegeand KAHERBelagaviKarnataka 590010India Department of Medical and Pediatric oncology and hematology Kerudi Cancer HospitalBagalkotKarnataka 587103India

The severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)belongs to the genus Beta coronavirus and the family of *** is a positive-sense,non-segmented single-strand RNA *** common types of human coronaviruses circulate globally,particularly in the fall and winter *** are responsible for 10%-30% of all mild upper respiratory tract infections in *** are 229E,NL63 of the Alfacoronaviridae family,OC43,and HKU1 of the Betacoronaviridae ***,there are three highly pathogenic human coronaviruses:SARS-CoV-2,Middle East respiratory syndrome coronavirus,and the latest pandemic caused by the SARS-CoV-2 *** viruses,including SARS-CoV-2,have the inherent tendency to ***-CoV-2 is still evolving in ***,due to the development of herd immunity,prior infection,use of medication,vaccination,and antibodies,the viruses are facing immune *** the replication process and due to immune pressure,the virus may undergo *** SARS-CoV-2 variants,including the variants of concern(VOCs),such as B.1.1.7(Alpha),B.1.351(Beta),B.1.617/B.1.617.2(Delta),P.1(Gamma),and B.1.1.529(Omicron)have been reported from various parts of the *** VOCs contain several important mutations;some of them are on the spike *** mutations may lead to enhanced infectivity,transmissibility,and decreased neutralization efficacy by monoclonal antibodies,convalescent sera,or *** may also lead to a failure of detection by molecular diagnostic tests,leading to a delayed diagnosis,increased community spread,and delayed *** searched PubMed,EMBASE,Covariant,the Stanford variant Database,and the CINAHL from December 2019 to February 2023 using the following search terms:VOC,SARS-CoV-2,Omicron,mutations in SARS-CoV-2,*** review discusses the various mutations and their impact on infectivity,transmissibility,and neutralization efficacy.

关键词： Variant of concern SARS-CoV-2 Omicron N501Y mutation E484K mutation

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Efficacy of Yisui granule(益髓颗粒)on myelodysplastic syndromes in SKM-1 mouse xenograft model through suppressing Wnt/β-catenin signaling pathway

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Journal of Traditional Chinese Medicine 2024年第1期44卷 78-87页

作者： WU Jieya HOU Li ZHANG Xiaoyuan Elizabeth Gullen GAO Chong WANG Jing Department of oncology and hematology Dongzhimen HospitalBeijing University of Chinese MedicineBeijing 100700China Department of Pharmacology Yale Medical SchoolNew HavenCT 06510USA Department of oncology Beijing Hospital of Traditional Chinese MedicineCapital Medical UniversityBeijing 100010China

OBJECTIVE:To unmask the underlying mechanisms of Yisui granule(益髓颗粒,YSG)for the treatment of Myelodysplastic syndromes(MDS).METHODS:Our study used an SKM-1 mouse xenograft model of MDS to explore the anti-tumor potential of YSG and its safety,assess its effect on overall survival(OS),and evaluate whether its mechanism is associated with the demethylation of the secreted frizzled related protein 5(s FRP5)gene and suppressing Wnt/β-catenin *** amplicon sequencing was applied to detect the level of methylation of the s FRP5 gene;western blotting,immunofluorescence staining,and real-time Polymerase Chain Reaction were performed to detect DNA methyltransferase 1(DNMT1),s FRP5,and other Wnt/β-catenin pathway-related m RNA and protein ***:The results showed that high-dosage YSG exerted an anti-tumor effect similar to that of decitabine,improved OS,and reduced long-term adverse effects in the long ***,YSG reduced the expression of DNMT1 methyltransferase,decreased the methylation,and increased the expression of the Wnt/β-catenin pathway antagonist-s ***,components of the Wnt/β-catenin pathway,including Wnt3a,β-catenin,c-Myc,and cyclin D1,were down-regulated in response to YSG,suggesting that YSG could treat MDS by demethylating the s FRP5 gene and suppressing the Wnt/β-catenin ***:Our findings demonstrated that YSG could be used alone or in combination with decitabine to improve outcomes in the MDS animal model,providing an alternative solution for treating MDS.

关键词： myelodysplastic syndromes Wnt signaling pathway beta catenin decitabine survival adverse effects sFRP5 gene methylation Yisui granule

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Plasmacytosis mimicking multiple myeloma in angioimmunoblastic T-cell lymphoma:A case report and review of literature

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World Journal of Clinical Cases 2024年第17期12卷 3226-3234页

作者： Chia-Ching Lin Hsu-Lin Lee Hsin-Yi Chuo Tuo-An Chen Ming-Yueh Liu Li-Mien Chen division of Cardiovascular Surgery Department of SurgeryKaohsiung Armed Forces General HospitalKaohsiung 802Taiwan division of Cardiovascular Surgery Department of SurgeryTri-Service General HospitalNational Defense Medical CenterTaipei 114Taiwan division of hematology and oncology Department of Internal MedicineTaichung Armed Forces General HospitalTaichung 411Taiwan division of hematology and oncology Department of Internal MedicineTri-Service General HospitalNational Defense Medical CenterTaipei 114Taiwan Department of Internal Medicine Taichung Armed-Forces General HospitalTaichung 411Taiwan Department of Pathology Taichung Armed-Forces General HospitalTaichung 411Taiwan Department of Radiation oncology Taichung Armed-Forces General HospitalTaichung 411Taiwan Department of Radiation oncology Tri-Service General HospitalNational Defense Medical CenterTaipei 114Taiwan

BACKGROUND Angioimmunoblastic T-cell lymphoma(AITL)is a common subtype of peripheral T-cell *** half of patients with AITL may concurrently present with *** numbers of plasma cells in the bone marrow are commonly observed at *** tumors mimic plasma cell myelomas,hindering a conundrum of clinical diagnoses and potentially delaying appropriate *** SUMMARY A 78-year-old woman experienced poor appetite,weight loss of 5 kg,fatigue 2 months before presentation,and shortness of breath 2 d before presentation,but no fever or night *** examination revealed splenomegaly and many palpable masses over the bilateral axillary regions,approximately>2 cm in size,with rubbery consistency and no *** tests revealed anemia and thrombocytopenia,lactate dehydrogenase level of 153 U/L,total protein level of 10.9 g/dL,albumin to globulin ratio of 0.2,and immunoglobulin G level more than the upper limit of 3000 mg/*** free kappa and lambda light chain concentrations were 451 and 614 mg/L,respectively.A pathological examination confirmed the diagnosis of *** initial treatment was the cyclophosphamide,epirubicin,vincristine,and prednisolone *** this treatment,pleural effusion was controlled,and the patient was discharged in a stable condition and followed up in our outpatient *** This report highlights the importance of differentiating reactive plasmacytosis from plasma cell myeloma in patients with hypergammaglobulinemia.A precise diagnosis of AITL requires a comprehensive evaluation,involving clinical,immunophenotypic,and histological findings conducted by a multidisciplinary team to ensure appropriate treatment.

关键词： Angioimmunoblastic T-cell lymphoma Plasmacytosis Multiple myeloma Lymphoma,Hypergammaglobulinemia Case report

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Jianpi Decoction Combined with Medroxyprogesterone Acetate Alleviates Cancer Cachexia and Prevents Muscle Atrophy by Directly Inhibiting E3 Ubiquitin Ligase

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Chinese Journal of Integrative Medicine 2024年第6期30卷 499-506页

作者： LI Qi KONG Zhao-di WANG Huan GU Hong-hui CHEN Zhong Li Shi-guang CHEN Yi-qi CAI Yu YANG Zhen-jiang Department of oncology and hematology Shenzhen Traditional Chinese Medicine HospitalShenzhenGuangdong Province518033China College of Pharmacy/International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education(MOE)of China Jinan UniversityGuangzhou510632China Guangdong Key Lab of Traditional Chinese Medicine Information Technology Jinan UniversityGuangzhou510632China

ObjectiveTo provide comprehensive evidence for the anti-cancer cachexia effect of Jianpi Decoction(JP)and to explore its mechanism of anti-cancer *** mouse model of colon cancer(CT26)-induced cancer cachexia(CC)was used to investigate the anti-CC effect of JP combined with medroxyprogesterone acetate(MPA).Thirty-six mice were equally divided into 6 groups:normal control,CC,MPA(100 mg·kg^(−1)·d^(−1)),MPA+low-dose(20 mg·kg^(−1)·d^(−1))JP(L-JP),MPA+medium-dose(30 mg·kg^(−1)·d^(−1))JP(M-JP),and MPA+high-dose(40 mg·kg^(−1)·d^(−1))JP(H-JP)*** successful modeling,the mice were administered by gavage for 11 *** body weight and tumor volume were measured and recorded every 2 d starting on the 8th day after *** liver,heart,spleen,lung,kidney,tumor and gastrocnemius muscle of mice were collected and *** pathological changes of the tumor was observed,and the cross-sectional area of the gastrocnemius muscle was *** protein expressions of STAT3 and E3 ubiquitinase in the gastrocnemius muscle were measured by Western *** addition,an in vitro C2C12 myotube formation model was established to investigate the role of JP in hindering dexamethasone-induced muscle *** vitro experiments were divided into control,model,and JP serum *** 2-d administration,microscopic photographs were taken and myotube diameters were *** blot was performed to measure the protein expressions of STAT3 and E3 *** combined with MPA restored tumor-induced weight loss(P<0.05,***)and muscle fiber size(P<0.01,***).Mechanistically,JP reduced the expression of atrophy-related proteins MuRF1 and MAFbx in tumor-induced muscle atrophy in vivo(P<0.05,***).In addition,JP reduced the expression of atrophy-related proteins MuRF1 and MAFbx and p-STAT3 phosphorylation(P<0.05 or P<0.01 *** group)in C2C12 myotubes treated with dexamethasone in *** of JP combined with MPA restores t

关键词： cancer cachexia muscle atrophy Jianpi Decoction Chinese medicine E3 ubiquitin ligases

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