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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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Exploiting the potential of the ubiquitin-proteasome system in overcoming tyrosine kinase inhibitor resistance in chronic myeloid leukemia

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Genes & Diseases 2024年第5期11卷 140-162页

作者： Xudong Li Wei Li Yanli Zhang Linping Xu Yongping Song department of hematology Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer HospitalZhengzhouHenan 450008China Academy of Medical Sciences Zhengzhou UniversityZhengzhouHenan 450052China department of hematology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052China

The advent of tyrosine kinase inhibitors(TKI)targeting BCR-ABL has drastically changed the treatment approach of chronic myeloid leukemia(CML),greatly prolonged the life of CML patients,and improved their ***,TKI resistance is still a major problem with CML patients,reducing the efficacy of treatment and their quality of *** resistance is mainly divided into BCR-ABL-dependent and BCR-ABL-independent ***,the main clinical strategy addressing TKI resistance is to switch to newly developed ***,data have shown that these new drugs may cause serious adverse reactions and intolerance and cannot address all resistance ***,finding new therapeutic targets to overcome TKI resistance is crucial and the ubiquitin-proteasome system(UPS)has emerged as a *** UPS mediates the degradation of most proteins in organisms and controls a wide range of physiological *** recent years,the study of UPS in hematological malignant tumors has resulted in effective treatments,such as bortezomib in the treatment of multiple myeloma and mantle cell *** CML,the components of UPS cooperate or antagonize the efficacy of TKI by directly or indirectly affecting the ubiquitination of BCR-ABL,interfering with CML-related signaling pathways,and negatively or positively affecting leukemia stem *** of these molecules may help overcome TKI resistance and treat *** this review,the mechanism of TKI resistance is briefly described,the components of UPS are introduced,existing studies on UPS participating in TKI resistance are listed,and UPS as the therapeutic target and strategies are discussed.

关键词： Chronic myeloid leukemia Deubiquitinases E3 ligase PROTAC TKI resistance Ubiquitin-proteasome system

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Haploidentical hematopoietic cell transplantation with or without an unrelated cord blood unit for adult acute myeloid leukemia:a multicenter,randomized,open-label,phase 3 trial

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2669-2678页

作者： Biqi Zhou Jia Chen Tianhui Liu Yishan Ye Yanming Zhang Yiyang Ding Hong Liu MingQing Zhu Xiao Ma Xiaoli Li Longfei Zhao Zhihong Lin He Huang Yang Xu Depei Wu National Clinical Research Center for Hematologic Diseases Jiangsu Institute of HematologyThe First Affiliated Hospital of Soochow UniversitySuzhouChina Institute of Blood and Marrow Transplantation Collaborative Innovation Center of HematologySoochow UniversitySuzhouChina Bone Marrow Transplantation Center The First Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiangChina department of hematology The Affiliated Huai’an Hospital of Xuzhou Medical University and The Second People’s Hospital of Huai’anHuai’anChina Soochow Hopes hematology hospital SuzhouChina department of hematology Hygeia Suzhou Yongding HospitalSuzhouChina

Coinfusion of unrelated cord blood(UCB)units in haploidentical hematopoietic cell transplantation(haplo-HCT)(haplo-cord HCT)for hematopoietic malignancies showed promising results in previous reports,but the efficiency of haplo-cord HCT in acute myeloid leukemia(AML)still lacks sufficient *** multicenter,randomized,phase 3 trial(*** NCT03719534)aimed to assess the efficacy and safety of haplo-cord HCT in AML patients.A total of 268 eligible patients aged 18-60 years,diagnosed with measurable residual disease in AML(excluding acute promyelocytic leukemia),with available haploidentical donors and suitable for allotransplantation,were randomly allocated(1:1)to receive haplo-cord HCT(n=134)or haplo-HCT(n=134).The 3-year overall survival(OS)was the primary endpoint in this *** median follow-up was 36.50 months(IQR 24.75-46.50).The 3-year OS of Haplo-cord HCT group was better than haplo-HCT group(80.5%,95%confidence interval[CI]:73.7-87.9 vs.67.8%95%CI 60.0-76.5,p=0.013).Favorable progression-free survival(70.3%,95%CI 62.6-78.8 vs.57.6%,95%CI 49.6-67.0,p=0.012)and cumulative incidence of relapse(12.1%,95%CI 12.0-12.2 vs.30.3%,95%CI 30.1-30.4,p=0.024)were observed in haplo-cord HCT *** 3-4 adverse events(AEs)within two years posttransplantation in the two groups were ***-cord HCT patients exhibited a faster cumulative incidence of neutrophil recovery(p=0.026)and increased T-cell reconstitution in the early period ***-cord HCT can improve OS in AML patients without excessive AEs,which may exert additional benefits for recipients of haplo-HCT.

关键词： hematopoietic acute phase

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Post-acute ischemic stroke hyperglycemia aggravates destruction of the blood-brain barrier

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Neural Regeneration Research 2024年第6期19卷 1344-1350页

作者： Tianqi Xu Jianhong Yang Yao Xu Xiaofeng Wang Xiang Gao Jie Sun Chenhui Zhou Yi Huang department of Neurology The First Affiliated Hospital of Ningbo University department of General Surgery The First Affiliated Hospital of Ningbo University department of Neurosurgery The First Affiliated Hospital of Ningbo University Key Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province

Post-acute ischemic stroke hyperglycemia increases the risk of hemorrhagic transformation, which is associated with blood-brain barrier disruption. Brain microvascular endothelial cells are a major component of the blood-brain barrier. Intercellular mitochondrial transfer has emerged as a novel paradigm for repairing cells with mitochondrial dysfunction. In this study, we first investigated whether mitochondrial transfer exists between brain microvascular endothelial cells, and then investigated the effects of post-acute ischemic stroke hyperglycemia on mitochondrial transfer between brain microvascular endothelial cells. We found that healthy brain microvascular endothelial cells can transfer intact mitochondria to oxygen glucose deprivation-injured brain microvascular endothelial cells. However, post-oxygen glucose deprivation hyperglycemia hindered mitochondrial transfer and exacerbated mitochondrial dysfunction. We established an in vitro brain microvascular endothelial cell model of the blood-brain barrier. We found that post-acute ischemic stroke hyperglycemia reduced the overall energy metabolism levels of brain microvascular endothelial cells and increased permeability of the blood-brain barrier. In a clinical study, we retrospectively analyzed the relationship between post-acute ischemic stroke hyperglycemia and the severity of hemorrhagic transformation. We found that post-acute ischemic stroke hyperglycemia serves as an independent predictor of severe hemorrhagic transformation. These findings suggest that post-acute ischemic stroke hyperglycemia can aggravate disruption of the blood-brain barrier by inhibiting mitochondrial transfer.

关键词： acute ischemic stroke blood-brain barrier brain microvascular endothelial cells mitochondrial transfer stress hyperglycemia

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Predictive value of neutrophil-to-lymphocyte ratio in coronary chronic total occlusion patients

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Journal of Geriatric Cardiology 2024年第5期21卷 542-549页

作者： Qian LI Yue YU Ya-Qiong ZHOU Yi ZHAO Jin WU Yuan-Jing WU Bin DU Pei-Jian WANG Tao ZHENG department of Cardiovascular Medicine the First Affiliated Hospital of Xi’an Jiaotong UniversityXi’anChina department of Cardiology First Affiliated Hospital of Chengdu Medical CollegeChengduChina department of Neurology the First Affiliated Hospital of Xi’an Jiaotong UniversityXi’anChina

BACKGROUND The neutrophil to lymphocyte ratio(NLR)has been reported as a novel predictor for atherosclerosis and car-diovascular *** study aimed to determine the effects of NLR on long-term clinical outcomes of chronic total occlusion(CTO)*** A total of 670 patients with CTO who met the inclusion criteria were included at the end of the follow-up *** were divided into tertiles according to their baseline NLR levels at admission:low(n=223),intermediate(n=223),and high(n=224).The incidence of major adverse cardiac events(MACEs)during the follow-up period,including all-cause death,nonfatal myocardial infarction(MI),or ischemia-driven revascularization,were compared among the three *** Major adverse cardiac events were observed in 27 patients(12.1%)in the low tertile,40(17.9%)in the intermediate tertile,and 61(27.2%)in the high NLR tertile(P<0.001).Kaplan-Meier analysis demonstrated a significantly higher incidence of MACE,ischemia-driven coronary revascularization,non-fatal MI,and mortality in patients within the high tertile than those in the low and intermediate groups(all P<0.001).Multivariable COX regression analysis showed that the high tertile of baseline NLR level showed a strong association with the risk of MACE(hazard ratio[HR]=2.21;95%confidence interval[CI]:1.21-4.03;P=0.009),ischemia-driven coronary revascularization(HR=3.19;95%CI:1.56-6.52;P=0.001),MI(HR=2.61;95%CI:1.35-5.03;P=0.043)and mortality(HR=3.78;95%CI:1.65-8.77;P=0.001).CONCLUSION Our findings suggest that NLR is an inexpensive and readily available biomarker that can independently pre-dict cardiovascular risk in patients with CTO.

关键词： patients coronary occlusion

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Ginsenoside Rd Induces Differentiation of Myeloid Leukemia Cells via Regulating ERK/GSK-3βSignaling Pathway

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Chinese Journal of Integrative Medicine 2024年第7期30卷 588-599页

作者： JIANG Yu-xia ZHAO Yan-na YU Xiao-ling YIN Li-ming department of hematology Tongde Hospital of Zhejiang ProvinceHangzhou310012China Institute of hematology Research the First Affiliated Hospital of Zhejiang Chinese Medical University(Zhejiang Provincial Hospital of Chinese Medicine)Hangzhou310006China

Objective To investigate the role of ginsenoside Rd(GRd)in acute myeloid leukemia(AML)cell *** AML cells were treated with GRd(25,50,100 and 200µg/mL),retinoic acid(RA,0.1g/L)and PD98059(20 mg/mL)for 72 h,cell survival was detected by methylthiazolyldiphenyl-tetrazolium bromide and colony formation assays,and cell cycle was detected by flow *** morphology and differentiation were observed by Wright-Giemsa staining,peroxidase chemical staining and cellular immunochemistry assay,*** protein expression levels of GATA binding protein 1(GATA-1),purine rich Box-1(PU.1),phosphorylated-extracellular signal-related kinase(p-ERK),ERK,phosphorylated-glycogen synthase kinase-3β(p-GSK3β),GSK3βand signal transducer and activator of transcription 1(STAT1)were detected by Western ***-six mice were randomly divided into 3 groups using a random number table:model control group(non-treated),GRd group[treated with 200 mg/(kg·d)GRd]and homoharringtonine(HTT)group[treated with 1 mg/(kg·d)HTT].A tumor-bearing nude mouse model was established,and tumor weight and volume were *** of subcutaneous tumor tissue were observed after hematoxylin and eosin ***1 and GATA-1 expressions were detected by immunohistochemical *** The cell survival was inhibited by GRd in a dose-dependent manner and GRd caused G0/G1 cell arrest(p<0.05).GRd treatment induced leukemia cell differentiation,showing increased expressions of peroxidase and specific proteins concerning erythrogenic or granulocytic differentiation(p<0.05).GRd treatment elicited upregulation of p-ERK,p-GSK-3βand STAT1 expressions in cells,and reversed the effects of PD98059 on inhibiting the expressions of peroxidase,GATA-1 and PU.1(P<0.05).After GRd treatment,tumor weight and volume of mice were decreased,and tumor cells underwent massive apoptosis and necrosis(P<0.05).WT1 level was decreased,and GATA-1 level was significantly increased in subcutaneous tumor ti

关键词： ginsenoside Rd myeloid leukemia survival differentiation extracellular signal-related kinase signaling pathway

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Immune cells in the B-cell lymphoma microenvironment:From basic research to clinical applications

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Chinese Medical Journal 2024年第7期137卷 776-790页

作者： Wenli Zhang Mengmeng Liu Wei Li Yongping Song department of hematology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052China department of hematology Henan Provincial Hematology HospitalZhengzhouHenan 450000China Academy of Medical Sciences Zhengzhou UniversityZhengzhouHenan 450052China department of Research and Foreign Affairs The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer HospitalZhengzhouHenan 450008China

B-cell lymphoma is a group of hematological malignancies characterized by variable genetic and biological features and clinical *** tumor microenvironment(TME)is a complex network in tumors,which consists of surrounding blood vessels,extracellular matrix,immune and non-immune cells,and signaling *** evidence has shown that the TME,especially immune cells within,is a double-edged sword,acting either as a tumor killer or as a promoter of tumor *** pro-tumor activities are driven by subpopulations of immune cells that express typical markers but have unique transcriptional characteristics,making tumor-associated immune cells good targets for human anti-cancer therapy by ablating immunosuppressive cells or enhancing immune-activated ***,exploring the role of immune cells in the TME provides distinct insights for immunotherapy in B-cell *** this review,we elucidated the interaction between immune cells and tumor cells and their function in the initiation,progression,and prognosis of B-cell lymphoma,from preclinical experiments to clinical ***,we outlined potential therapeutic approaches and discussed the potential clinical value and future perspectives of targeting immune cells in patients with B-cell lymphoma.

关键词： Tumor microenvironment B-cell lymphoma Immune cells Immunotherapy Targeted therapy

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NIR-triggered on-site NO/ROS/RNS nanoreactor:Cascade-amplified photodynamic/photothermal therapy with local and systemic immune responses activation

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Opto-Electronic Advances 2024年第6期7卷 58-73页

作者： Ziqing Xu Yakun Kang Jie Zhang Jiajia Tang Hanyao Sun Yang Li Doudou He Xuan Sha Yuxia Tang Ziyi Fu Feiyun Wu Shouju Wang Laboratory of Molecular Imaging Department of RadiologyThe First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China department of Breast Surgery The First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China department of Women&Children Research Center The First Affiliated HospitalNanjing Medical UniversityNanjing 210029China

Photothermal and photodynamic therapies(PTT/PDT)hold promise for localized tumor treatment,yet their full potential is hampered by limitations such as the hypoxic tumor microenvironment and inadequate systemic immune *** these challenges,we present a novel near-infrared(NIR)-triggered RNS nanoreactor(PBNO-Ce6)to amplify the photodynamic and photothermal therapy efficacy against triple-negative breast cancer(TNBC).The designed PBNOCe6 combines sodium nitroprusside-doped Prussian Blue nanoparticles with Chlorin e6 to enable on-site RNS production through NIR-induced concurrent NO release and ROS *** not only enhances tumor cell eradication but also potentiates local and systemic antitumor immune responses,protecting mice from tumor *** in vivo evaluations revealed that treatment with PBNO-Ce6 leads to a remarkable 2.7-fold increase in cytotoxic T lymphocytes and a 62%decrease in regulatory T cells in comparison to the control PB-Ce6(Prussian Blue nanoparticles loaded with Chlorin e6),marking a substantial improvement over traditional PTT/*** such,the PBNO-Ce6 nanoreactor represents a transformative approach for improving outcomes in TNBC and potentially other malignancies affected by similar barriers.

关键词： photothermal therapy photodynamic therapy nitric oxide reactive nitrogen species triple-negative breast cancer immune response nanoreactor

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Resilience provides mediating effect of resilience between fear of progression and sleep quality in patients with hematological malignancies

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World Journal of Psychiatry 2024年第4期14卷 541-552页

作者： Yuan Tian Ying-Li Wang department of hematology The First Affiliated Hospital of Jinzhou Medical UniversityJinzhou 121000Liaoning ProvinceChina department of Cardiology The First Affiliated Hospital of Jinzhou Medical UniversityJinzhou 121000Liaoning ProvinceChina

BACKGROUND Hematological tumors are common malignant tumors,with high morbidity and mortality *** patients with hematological malignancies develop sleep disorders that seriously affect their life and health because of acute onset of disease,rapid progression,high recurrence rates,complex treatment methods,and treatment *** To explore the mediating effect of resilience on fear of disease progression and sleep quality in patients with hematological *** A cross-sectional analysis of 100 patients with hematological malignancies,treated in the first affiliated hospital of Jinzhou Medical University between August 2022 and August 2023,was *** were assessed using a general data survey,a simplified scale for the fear of progression(FoP)of disease,a resilience scale,and the Pittsburgh Sleep Quality *** analysis was conducted to determine the relationship between various patient characteristics and FoP,resilience,and sleep ***’s correlation analysis was used to examine the correlations between mental resilience,FoP,and sleep *** The total FoP score mean value in patients with hematological malignancies was 38.09±5.16;the total resilience score mean value was 40.73±7.04;and the Pittsburgh Sleep Quality Index score mean value was 10.72±***,resilience,and sleep quality of the patients were associated with family per capita monthly income and patient education level(P<0.05).Spearman correlation analysis revealed that FoP was negatively correlated with resilience and sleep quality scores(r=-0.560,-0.537,P<0.01),respectively,and resilience was significantly associated with sleep quality scores(r=0.688,P<0.01).Mediation analysis showed that the mediating effect of resilience between FoP and sleep quality in patients with hematological malignancies was-0.100 and accounted for 50.51%of the total *** indicated that FoP directly and indirectly affected sleep quality through the mesomeric eff

关键词： Resilience Blood tumor Fear of progression Sleep quality Mediating effect

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Impact of comorbid subthreshold depressive symptoms on cancerrelated fatigue and complications in adults with leukemia

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World Journal of Psychiatry 2024年第7期14卷 1009-1016页

作者： Yue-Xian Liu Juan Wang department of hematology Central Hospital Affiliated to Shandong First Medical UniversityJinan 250013Shandong ProvinceChina

BACKGROUND Patients not only experience symptoms caused by cancer but also suffer from the accompanying psychological ***,these patients do not have high quality of *** to the World Health Organization,the incidence of leukemia in China in 2020 was 5.1/100000,the mortality rate was 3.3/100000,and the prevalence rate was 16.7/***,it is important to examine the influence of comorbid subthreshold depressive symptoms on leukemia *** To determine the impact of comorbid subthreshold depressive symptoms on cancer-related fatigue and complications in leukemia patients,thereby providing a basis for early diagnosis and treatment in clinical *** A questionnaire survey was conducted among leukemia patients admitted to a tertiary hospital in Xi'an,Shaanxi Province,China,from August 2022 to December *** with a score>16 on the Chinese Classification of Mental Disorders(CCMD-3)and a Hamilton Depression Rating Scale score of 8-17 were classified as the subthreshold depressive group(n=95),while 100 leukemia patients admitted during the same period were classified as the control *** were collected using Epidata 3.1 software,and comparisons were made between the two groups regarding general clinical data,the Piper Fatigue Scale(PFS),the Pittsburgh Sleep Quality Index(PSQI),the Numeric Rating Scale for pain assessment,laboratory indicators,and the occurrence of *** In this survey,120 leukemia patients with depression were preliminarily screened,95 patients with subthreshold depression were ultimately selected as the subthreshold depression group,and 100 leukemia patients admitted during the same period were enrolled as the normal *** of basic clinical data between the two groups revealed no significant differences in age,sex,body mass index,cognitive function,or comorbidity with other chronic ***,there were statistically significant differences in the use of radiotherapy

关键词： Subthreshold depression Leukemia Cancer-related fatigue Complications Minor depression

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