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Microbiome subsets determine tumor prognosis and molecular characteristics of clear-cell renal cell carcinoma:a multi-center integrated analysis of microbiome,metabolome,and transcriptome data

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Frontiers of Medicine 2024年第2期18卷 399-402页

作者： Wenjin Chen Xiuwu Pan Wang Zhou Da Xu Jiaxin Chen Keqin Dong Weijie Chen Brian Rini Xingang Cui department of Urology Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghai200092China department of Urology Third Affiliated Hospital of the Second Military Medical UniversityShanghai201805China Division of hematology Oncology Vanderbilt University Medical CenterNashvilleTN37232USA

Dear editor,Patients with clear-cell renal cell carcinoma(ccRCC)potentially have a high recurrence rate of more than 40%[1].Patients receive radical or partial nephrectomy,sometimes assisted by targeted therapies or/and immune checkpoint inhibitors(ICIs),to improve overall survival(OS)[2].Large-cohort studies and large-scale human tissue sequencing have provided a series of molecular subtyping methods for precision medicine-based ccRCC risk stratification and therapeutic regimens,such as ClearCode34,the prognostic risk predictor[3],and seven subsets for ICI and angiogenesis blockade outcomes[4].However,these subtyping results are all based on human genomes without including the host microbiota,which may be non-negligible genome components.

关键词： editor negligible characteristics

Successful treatment of Purpureocillium lilacinum pulmonary infection with isavuconazole: A case report

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World Journal of Clinical Cases 2024年第10期12卷 1772-1777页

作者： Xue-Lin Yang Jun-Yu Zhang Jian-Min Ren department of Emergency Medicine Lishui Central HospitalLishui 323000Zhejiang ProvinceChina department of hematology Lishui Central HospitalLishui 323000Zhejiang ProvinceChina department of Clinical Laboratory The Fifth Affiliated Hospital of Wenzhou Medical UniversityLishui 323000Zhejiang ProvinceChina

BACKGROUND Purpureocillium lilacinum(***)is a saprophytic fungus widespread in soil and *** a causative agent,it is very rarely detected in humans,most commonly in the *** SUMMARY In this article,we reported the case of a 72-year-old patient with chronic lymphocytic leukemia who was admitted with cough and *** tomography revealed an infection in the right lower *** lavage fluid culture and metagenomic next-generation sequencing were ultimately confirmed to have a pulmonary infection with *** was eventually discharged with good outcomes after treatment with *** Pulmonary infection with *** was exceedingly *** currently there are no definitive therapeutic agents,there are reports of high resistance to amphotericin B and fluconazole and good sensitivity to second-generation *** present report is the first known use of isavuconazole for pulmonary *** *** provides new evidence for the characterization and treatment of clinical *** lung infections.

关键词： Purpureocillium lilacinum Pulmonary infection Isavuconazole Case report

Therapeutic genome editing of an aberrant splice site inβ-thalassemia by CRISPR/Cas9 with multiple sgRNAs

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Genes & Diseases 2024年第1期11卷 15-18页

作者： Fei Yang Shuqian Xu Chao Huang Zhiqiang Shao Yuefen Hu Yang Yang Yongrong Lai Qing Ke Dan Liang Yuxuan Wu Shanghai Key Laboratory of Regulatory Biology Institute of Biomedical Sciences and School of Life SciencesEast China Normal UniversityShanghai 200241China department of Obstetrics and Gynecology The First Affiliated Hospital of Anhui Medical UniversityHefeiAnhui 230022China NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract(Anhui Medical university) HefeiAnhui 230032China department of hematology Qilu HospitalCheeloo College of MedicineShandong UniversityJinanShandong 250012China BRLMedicine Inc. Shanghai 201108China department of hematology The First Affiliated Hospital of Guangxi Medical UniversityNanningGuangxi 530000China department of Neurology The First Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310003China

Genetic mutations cause aberrant splicing,one of the important molecular mechanisms in human ***2-654,a mutation causing aberrant splicing ofβ-globin premRNA and contributing toβ-globin deficiency,is one of the most common diseases in Southeast Asia and China."In our previous work,we found a TTTV protospacer adjacent motif(PAM)by the Cas12a system and the editing efficiency of Ivs2-654 C>T achieving 76.7%.

关键词： CRISPR/Cas9 China thalassemia

Predictive value of T cell receptor repertoire profiling for immunosuppressive therapy in severe aplastic anemia

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Genes & Diseases 2024年第1期11卷 95-98页

作者： Cunte Chen Yuling Zhang Dongpei Lu Zelong Zhang Jun Yang Xiaowei Chen Ming Zhou Wenjian Mo Caixia Wang Qinghua Cai Yumiao Li Ruiqing Zhou Shilin Xu Wei Zhou Tingfen Deng Shiyi Pan Yanli Xu Shunqing Wang Yuping Zhang department of hematology Guangzhou First People's HospitalSouth China University of TechnologyGuangzhouGuangdong 510180China Guangzhou Junruikang Biotechnology Co. LtdGuangzhouGuangdong 510700China

Increasing evidence supports the hypothesis of autologous immune attack in severe aplastic anemia(SAA):the predominant role of activated cytotoxic T cells(CTL)expressing-interferon in inhibiting the growth of bone marrow(BM)cells,putative autoantigens,and oligoclonal expansion of CD8+T cells.1 For SAA patients,the definitive therapies are immunosuppressive therapy(IST)or hematopoietic stem transplantation(HSCT).

关键词： anemia aplastic interferon

Associations of serum D-dimer and glycosylated hemoglobin levels with third-trimester fetal growth restriction in gestational diabetes mellitus

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World Journal of Diabetes 2024年第5期15卷 914-922页

作者： Ying Zhang Teng Li Chao-Yan Yue Yun Liu department of Laboratory Medicine Obstetrics and Gynecology Hospital of Fudan UniversityShanghai 200011China department of Interventional Radiology The People’s Hospital of Weifang CityWeifang 261041Shandong ProvinceChina department of hematology The People’s Hospital of Weifang CityWeifang 261041Shandong ProvinceChina

BACKGROUND Gestational diabetes mellitus(GDM)is a special type of diabetes that commonly occurs in women during pregnancy and involves impaired glucose tolerance and abnormal glucose metabolism;GDM is diagnosed for the first time during pregnancy and can affect fetal growth and *** To investigate the associations of serum D-dimer(D-D)and glycosylated hemoglobin(HbA1c)levels with third-trimester fetal growth restriction(FGR)in GDM *** The clinical data of 164 pregnant women who were diagnosed with GDM and delivered at the Obstetrics and Gynecology hospital of Fudan university from January 2021 to January 2023 were analyzed *** these women,63 whose fetuses had FGR were included in the FGR group,and 101 women whose fetuses had normal body weights were included in the normal body weight group(normal group).Fasting venous blood samples were collected from the elbow at 28-30 wk gestation and 1-3 d before delivery to measure serum D-D and HbA1c levels for comparative *** diagnostic value of serum D-D and HbA1c levels for FGR was evaluated by receiver operating characteristic analysis,and the influencing factors of third-trimester FGR in GDM patients were analyzed by logistic *** Serum fasting blood glucose,fasting insulin,D-D and HbA1c levels were significantly greater in the FGR group than in the normal group,while the homeostasis model assessment of insulin resistance values were lower(P<0.05).Regarding the diagnosis of FGR based on serum D-D and HbA1c levels,the areas under the curves(AUCs)were 0.826 and 0.848,the cutoff values were 3.04 mg/L and 5.80%,the sensitivities were 81.0%and 79.4%,and the specificities were 88.1%and 87.1%,*** AUC of serum D-D plus HbA1c levels for diagnosing FGR was 0.928,and the sensitivity and specificity were 84.1%and 91.1%,*** D-D and HbA1c levels were risk factors for third-trimester FGR in GDM patients(P<0.05).CONCLUSION D-D and HbA1c levels can

关键词： Gestational diabetes mellitus D-dimer Hemoglobin Fetal growth restriction Fasting blood glucose

Low-dose immune tolerance induction for severe hemophilia A inhibitor patients:Immunosuppressants are generally not necessary for inhibitor-titer below 200 BU/mL

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Pediatric Investigation 2024年第2期8卷 91-100页

作者： Zhengping Li Jie Sun Zekun Li Zhenping Chen Guoqing Liu Wanru Yao Xiaoling Cheng Gang Li Yingzi Zhen Di Ai Yaohan Zhou Qianqian Mao Man-Chiu Poon Runhui Wu Hemophilia Comprehensive Care Center Hematology DepartmentHematology CenterBeijing Key Laboratory of Pediatric Hematology-OncologyKey Laboratory of Major Diseases in ChildrenNational Key Discipline of Pediatrics(Capital Medical University)Ministry of EducationBeijing Children’s HospitalCapital Medical UniversityNational Center for Children’s HealthBeijingChina Hematologic Disease Laboratory Hematology DepartmentHematology CenterBeijing Key Laboratory of Pediatric Hematology-OncologyKey Laboratory of Major Diseases in ChildrenNational Key Discipline of Pediatrics(Capital Medical University)Ministry of EducationBeijing Pediatric Research InstituteBeijing Children’s HospitalCapital Medical UniversityNational Center for Children’s HealthBeijingChina department of Pharmacy Beijing Children’s HospitalCapital Medical UniversityNational Center for Children’s HealthBeijingChina departments of Medicine Pediatrics and OncologyUniversity of Calgary Cumming School of MedicineCalgaryCanada

Importance:It remained unclear that the efficacy comparison between low-dose immune tolerance induction(LD-ITI)incorporating immunosuppressants(IS)when severe hemophilia A(SHA)patients had inhibitor-titer≥200 Bethesda Units(BU)/mL(LD-ITI-IS200 regimen)and LD-ITI combining with IS when SHA patients had inhibitor-titer≥40 BU/mL(LD-ITI-IS40 regimen).Objective:To compare the efficacy of the LD-ITI-IS200 regimen with that of the LD-ITI-IS40 regimen for SHA patients with high-titer ***:A prospective cohort study on patients receiving LD-ITI-IS200 compared to those receiving LD-ITI-IS40 from January 2021 to December *** received LD-ITI[FVIII 50 IU/kg every other day].IS(rituximab+prednisone)was added when peak inhibitor tier≥200 BU/mL in the LD-ITI-IS200 regimen and≥40 BU/mL in the LD-ITI-IS40 *** is defined as a negative inhibitor plus FVIII recovery≥66%of the ***:We enrolled 30 patients on LD-ITI-IS200 and 64 patients on LD-ITI-IS40,with similar baseline clinical characteristics.A lower IS-use rate was discovered in the LD-ITI-IS200 regimen compared to the LD-ITI-IS40 regimen(30.0%vs.62.5%).The two regimens(LD-ITI-IS200 ***-ITI-IS40)had similar success rate(70.0%vs.79.7%),median time to success(9.4 vs.10.6 months),and annualized bleeding rate during ITI(3.7 vs.2.8).The cost to success was lower for LD-ITI-IS200 than for LD-ITI-IS40(2107 vs.3256 US Dollar/kg).Among patients with peak inhibitor-titer 40-199 BU/mL,10 non-IS-using(on LD-ITI-IS200 regimen)and 28 IS-using(on LD-ITI-IS40 regimen)had similar success rates(70.0%vs.78.6%)and time to success(9.0 vs.8.8 months).Interpretation:In LD-ITI,IS are not necessary for inhibitor titer<200 BU/mL.

关键词： Hemophilia A High-titer inhibitor Immune tolerance induction Immunosuppressant Low-dose

HIF-1α signaling: Essential roles in tumorigenesis and implications in targeted therapies

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Genes & Diseases 2024年第1期11卷 234-251页

作者： Yan Zhao Cheng Xing Yating Deng Can Ye Hongling Peng department of hematology The Second Xiangya HospitalCentral South UniversityChangshaHunan 410011China Hunan Key Laboratory of Tumor Models and Individualized Medicine The Second Xiangya HospitalCentral South UniversityChangshaHunan 410011China Hunan Engineering Research Center of Cell Immunotherapy for Hematopoietic Malignancies The Second Xiangya HospitalCentral South UniversityChangshaHunan 410011China

The hypoxic microenvironment is an essential characteristic of most malignant ***,hypoxia-inducible factor-1 alpha(HIF-1a)is a key regulatory factor of cellular adaptation to hypoxia,and many critical pathways are correlated with the biological activity of organisms via *** the intra-tumoral hypoxic environment,HIF-1αis highly expressed and contributes to the malignant progression of tumors,which in turn results in a poor prog-nosis in ***,it has been indicated that HiF-1αinvolves in various critical pro-cesses of life events and tumor development via regulating the expression of HiF-1a target genes,such as cell proliferation and apoptosis,angiogenesis,glucose metabolism,immune response,therapeutic resistance,*** from solid tumors,accumulating evidence has re-vealed that HiF-1αis also closely associated with the development and progression of hemato-logical malignancies,such as leukemia,lymphoma,and multiple *** inhibition of HiF-1a can facilitate an increased sensitivity of patients with malignancies to relevant ther-apeutic *** the review,we elaborated on the basic structure and biological functions of HIF-1a and summarized their current role in various *** is expected that they will have future potential fortargeted therapy.

关键词： Angiogenesis Hematological malignancies Hypoxia-inducible factor-1 alpha(HIF-1α) Immune escape Targeted therapy

Repurposing disulfiram with CuET nanocrystals:Enhancing anti-pyroptotic effect through NLRP3 inflammasome inhibition for treating inflammatory bowel diseases

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2698-2715页

作者： Xueming Xu Yuanfeng Han Jiali Deng Shengfeng Wang Shijie Zhuo Kai Zhao Wenhu Zhou hematology and department of Critical Care Medicine The Third Xiangya HospitalCentral South UniversityChangsha 410013China Xiangya School of Pharmaceutical Sciences Central South UniversityChangsha 410013China Hunan Chidren's hospital Changsha 410007China department of Pharmacy The Third Xiangya HospitalCentral South UniversityChangsha 410013China Key Laboratory of Biological Nanotechnology of National Health Commission Changsha 410008China

Drug repurposing offers a valuable strategy for identifying new therapeutic applications for existing ***,disulfiram(DSF),a drug primarily used for alcohol addiction treatment,has emerged as a potential treatment for inflammatory diseases by inhibiting pyroptosis,a form of programmed cell *** therapeutic activity of DSF can be further enhanced by the presence of Cu^(2+),although the underlying mechanism of this enhancement remains *** this study,we investigated the mechanistic basis of Cu^(2+)-induced enhancement and discovered that it is attributed to the formation of a novel copper ethylthiocarbamate(CuET)*** exhibited significantly stronger anti-pyroptotic activity compared to DSF and employed a distinct mechanism of ***,despite its potent activity,CuET suffered from poor solubility and limited permeability,as revealed by our druggability *** overcome these intrinsic limitations,we developed a scalable method to prepare CuET nanocrystals(CuET NCs)using a metal coordination-driven self-assembly *** studies demonstrated that CuET NCs exhibited a 6-fold improvement in ***,CuET NCs exhibited high biodistribution in the intestine,suggesting their potential application for the treatment of inflammatory bowel diseases(IBDs).To evaluate their therapeutic efficacy in vivo,we employed a murine model of DSS-induced colitis and observed that CuET NCs effectively attenuated inflammation and ameliorated colitis *** findings highlight the discovery of CuET as a potent anti-pyroptotic agent,and the development of CuET NCs represents a novel approach to enhance the druggability of CuET.

关键词： Drug repurposing Pyroptosis Nanoparticles Bioavailability Disulfiram DSS-induced colitis NLRP3 inflammasome CuET

Parenteral iron therapy in children with iron deficiency anemia

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World Journal of Clinical Cases 2024年第13期12卷 2138-2142页

作者： Jelena Roganovic department of Pediatric hematology and Oncology Children’s Hospital Zagreb10000 ZagrebCroatia Faculty of Biotechnology and Drug Development University of RijekaRijeka 51000Croatia

Iron deficiency anemia(IDA)continues to be a global public health *** iron is the universally accepted first-line therapy,and most children have a prompt and favorable response to oral *** subsets of children who fail to respond due to intolerance,poor adherence,or inadequate intestinal absorption,parenteral iron is *** numerous studies in adults with IDA of diverse etiologies,pediatric studies on parenteral iron use are very *** mostly retrospective and small,these studies have documented the efficacy and safety profile of intravenous iron *** this editorial the author comments on the most important published data and underscores the need to seriously consider parenteral iron use in children unresponsive to oral therapy.

关键词： Anemia Iron deficiency Intravenous iron Iron deficiency anemia Children