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Effect of insulin and metformin on methylation and glycolipid metabolism of peroxisome proliferator-activated receptor γcoactivator-1A of rat offspring with gestational diabetes mellitus

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Asian Pacific Journal of Tropical Medicine 2016年第1期9卷 89-93页

作者： Ai-Qin Song Li-Rong Sun Yan-Xia Zhao Yan-Hua Gao Lei Chen Department of Pediatric Hematology Affiliated Hospital of Qingdao University

Objective:To discuss the effect of insulin and metformin on amethylation and glycolipid metabolism of peroxisome proliferator-activated receptor γ coactivator-1A(PPARGC1A) of rat offspring with gestational diabetes mellitus(GDM).Methods:A total of 45 pregnant rats received the intraperitoneal injection of streptozotocin to establish the pregnant rat model of GDM.A total of 21 pregnant rats with GDM were randomly divided into three groups,with 7ruts in each group,namely the insulin group,metformin group and control group.Rats in the insulin group received the abdominal subcutaneous injection of 1 mL/kg recombinant insulin glargine at 18:00 every day.Rats in the metformin group received the intragastric infusion of metformin hydrochloride at 18:00 every day,with the first dose of 300 mg/kg.The doses of two groups were adjusted every 3 d to maintain the blood glucose level at 2.65-7.62 mmol/L.Rats in the control group received the intragastric infusion of 1 mL normal saline at 18:00 every day.After the natural delivery of pregnant rats.10 offspring rats were randomly selected from each group.At birth,4 wk and 8 wk after the birth of offspring rats,the weight of offspring rats was measured.The blood glucose level of offspring rats was measured at 4wk and 8 wk,while the level of serum insulin,triglyceride and leptin was measured at 8 wk.Results:The weight of offspring rats at birth in the insulin group and metformin group was significantly lower than the one in the control group(P0.05).The fasting blood glucose and random blood glucose in the insulin group and metformin group at 4 wk and 8 wk were all significantly lower than ones in the control group(P0.05).The expression of PPARGC1 A mRNA in the insulin group and metformin group was significantly higher and the methylation level of PPARGC1 A was significantly lower than the one in the control

关键词： Insulin Metformin Gestational diabetes mellitus Peroxisome proliferator-activated receptor γ coactivator-1 A Methylation Glycolipid metabolism

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Physician approaches to drug shortages: Results of a national survey of pediatric hematologist/oncologists

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World Journal of Clinical Oncology 2017年第4期8卷 336-342页

作者： Jill C Beck Baojiang Chen Bruce G Gordon Department of Pediatric Hematology/Oncology University of Nebraska Medical Center

AIM To evaluate personnel involved in scarce drug prioritization and distribution and the criteria used to inform drug distribution during times of shortage among pediatric hematologists/oncologists. METHODS Using the American Society of pediatric hematology/Oncology(ASPHO) membership list, a 20 question survey of pediatric hematologists/oncologists was conducted via email to evaluate personnel involved in scarce drug prioritization and distribution and criteria used to inform scarce drug distribution. RESULTS Nearly 65% of the 191 study respondents had patients directly affected by drug shortages. Most physicians find out about shortages from the pharmacist(n = 179, 98%) or other doctors(n = 75, 41%). One third of respondents do not know if there is a program or policy for handling drug shortages at their institution. The pharmacist was the most commonly cited decision maker for shortage drug distribution(n = 128, 70%), followed by physicians(n = 109, 60%). One fourth of respondents did not know who makes decisions about shortage drug distribution at their institution. The highest priority criterion among respondents was use of the shortage drug for curative, rather than palliative intent and lowest priority criterion was order of arrival or first-come first-served.CONCLUSION Despite pediatric hematology/oncology physicians and patients being heavily impacted by drug shortages, institutional processes for handling shortages are lacking. There is significant disparity between how decisions for distribution of shortage drugs are currently made and how study respondents felt those decisions should be made. An institution-based, and more importantly, a societalapproach to drug shortages is necessary to reconcile these disparities.

关键词： pediatric hematology/oncology Chemotherapy Ethics

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Long-term outcome of tyrosine kinase inhibitor treatment in children and adolescents with newly diagnosed chronic myeloid leukemia in chronic phase

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Chinese Medical Journal 2021年第24期134卷 3009-3011页

作者： Yong-Zhi Zheng Jian Li Cai Chen Hao Zheng Dan-Hui Fu Jian-Da Hu department of hematology Fujian Institute of HematologyFujian Provincial Key Laboratory of HematologyFujian Medical University Union HospitalFuzhouFujian 350001China pediatric hematology department Fujian Institute of HematologyFujian Provincial Key Laboratory of HematologyFujian Medical University Union HospitalFuzhouFujian 350001China

Chronic myeloid leukemia(CML)is relatively rare in children,with an average annual incidence of 0.6 to 1.0 case per million in children<15 years and 2.2 cases per million in adolescents aged 15 to 19 years,accounting ... 详细信息

Chronic myeloid leukemia(CML)is relatively rare in children,with an average annual incidence of 0.6 to 1.0 case per million in childrenpediatric patients with chronic-phase CML(CML-CP).[2]However,IM treatment is discontinued in 25%to 29%of pediatric patients with CML-CP because of drug resistance or intolerance.[3]For such patients,second-generation tyrosine kinase inhibitors(2G-TKIs),including dasatinib and nilotinib,were approved by the FDA as first-and second-line therapies in 2017 and 2018,respectively.[2]However,given the rarity of this neoplasm and the lack of clinical trial data,treatments for pediatric CML follow the recommended adult regimen,and little is known about the long-term efficacy and safety of these treatments in children and adolescents.[2]Furthermore,there are few reports detailing the sequential use of IM as first-line treatment followed by 2G-TKIs as second-line therapy in Chinese pediatric patients with CML.Therefore,there is a strong need to investigate the long-term effects of IM treatment in a large cohort of Chinese pediatric patients.In this report,we retrospectively analyzed the long-term follow-up results of 58 pediatric patients with CML-CP treated with IM as first-line therapy and 2G-TKIs as second-line therapy in a single South China center.

关键词： adolescent myeloid treatment

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Homoharringtonine is a safe and effective substitute for anthracyclines in children younger than 2 years old with acute myeloid leukemia

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Frontiers of Medicine 2019年第3期13卷 378-387页

作者： Xiaoxiao Chen Yanjing Tang Jing Chen Ru Chen Longjun Gu Huiliang Xue Ci Pan Jingyan Tang Shuhong Shen Key Laboratory of pediatric hematology and Oncology Ministry of Health Department of Hematology and OncologyPediatric Translational Medicine InstituteShanghai Children's Medical CenterShanghai Jiao Tong University School of MedicineShanghai 200127China

Homoharringtonine (HHT),a plant alkaloid from Cephalotaxus harringtonia,exhibits a unique anticancer mechanism and has been widely used in China to treat patients with acute myeloid leukemia (AML) since the 1970s.Trial SCMC-AML-2009 presented herein was a randomized clinical study designed based on our previous findings that pediatric AML patients younger than two years old may benefit from HHT-containing chemotherapy regimens.Patients randomized to arm A were treated with a standard chemotherapy regimen comprising mainly of anthracyclines and cytarabine (Ara-C),whereas patients in arm B were treated with HHTcontaining regimens in which anthracyclines in all but the initial induction therapy were replaced by HHT.From February 2009 to November 2015,59 patients less than 2 years old with de novo AML (other than acute promyelocytic leukemia) were recruited.A total of 42 patients achieved a morphologic complete remission (CR) after the first course,with similar rates in both arms (70.6% vs.72.0%).At the end of the follow-up period,40 patients remained in CR and 5 patients underwent hematopoietic stem cell transplantation in CR,which could not be considered as events but censors.The 5-year event-free survival (EFS) was 60.2%± 9.6% for arm A and 88.0%± 6.5% for arm B (P=0.024).Patients in arm B experienced shorter durations of leukopenia,neutropenia,and thrombocytopenia and had a lower risk of infection during consolidation chemotherapy with high-dosage Ara-C.Consequently,the homoharringtonine-based regimen achieved excellent EFS and alleviated hematologic toxicity for children aged younger than 2 years with de novo AML compared with the anthracycline-based regimen.

关键词： homoharringtonine acute myeloid leukemia pediatrics

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A histone tale that enCOMPASSes pausing:new insights into the functional repertoire of H3K4me3

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Signal Transduction and Targeted Therapy 2023年第8期8卷 3555-3557页

作者： Thomas K.Albert Kornelius Kerl Department of Pediatric Hematology and Oncology University Children’s Hospital MuensterMuensterGermany

A recently published study in Nature provides compelling evidence for the involvement of the histone H3K4me3 modification in regulating RNA polymerase II(Pol II)pause-release and elongation.1 The expansion of the functional repertoire of this active chromatin mark and the elucidation of the molecular mechanisms behind it represents a major advance for the field,not least because the epigenetic factors involved are linked to a wide range of human pathologies.The term epigenetics derives from the Greek prefix“epi”and describes an inheritable regulatory state that manifests itself beyond the mere genetic information encoded in the DNA.

关键词： involvement functional insight

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A Retrospective Analysis of Intracranial Hemorrhage in Children with Hemophilia A

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Current Medical Science 2018年第5期38卷 875-879页

作者： Qun HU Ai ZHANG Ai-guo LILT Song-mi WANG Ya-qin WANG Liu-qing ZHANG Department of Pediatric Hematology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

To investigate the incidence,risk factors,clinical manifestations and prognosis of intracranial hemorrhage (ICH)in children with hemophilia A in a center of China, we conducted a retrospective analysis of 126 children with hemophilia A at our hospital in recent 4 years.Thirty-six children with hemophilia A (including 19 severe cases,and 17 moderate cases complicated with joint diseases)received low dose factor Ⅷ (FⅧ) prophylaxis,and none of them had ICH.However,13 cases of hemophilia A not given prophylaxis were complicated with ICH (12 severe cases,and 1 moderate case)and demonstrated an incidence of 10.3%(13/126)in all patients,and 28.6%(12/42)in severe cases.Of the 13 cases,9 severe ICH cases had a definite history of head injury,accounting for 69.2%.Headache was common in children >3 years,but somnolence,irritability, gaze or convulsions in children <3 years.The most common findings of cranial CT scan included intracranial hematoma (9/13),and less commonly observed were subependymal hemorrhage and intraventricular hemorrhage.After administration of FⅧ,all patients survived.Hematoma of 6 cases was observed during CT reexamination after 1-3 months. During the follow-up period,only one case had slight activity limitation on one side of the limb,but steadily recovered.Besides the decreased concentration of FⅧ,trauma is the most common risk factor of ICH in children with hemophilia A.The active treatment can improve the prognosis of ICH in children with hemophilia A.

关键词： hemophilia A intracranial hemorrhage children retrospective analysis

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Rhythmical massage improves autonomic nervous system function:a single-blind randomised controlled trial

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Journal of Integrative Medicine 2018年第3期16卷 172-177页

作者： Georg Seifert Jenny-Lena Kanitz Carolina Rihs Ingrid Krause Katharina Witt Andreas Voss department of pediatric Oncology and hematology Charité-Universit?tsmedizin Berlin Institute of Innovative Health Technologies Ernst-Abbe-Hochschule University of Applied Sciences

Background： Rhythmical massage therapy（RMT） is a massage technique used in anthroposophic medicine.Objective： The authors aimed to investigate the physiological action of RMT on the cardiovascular system by analysing heart rate variability（HRV）.Design, setting, participants and intervention： This study was a randomised, controlled and single-blinded trial, involving 44 healthy women（mean age：（26.20 ± 4.71） years）. The subjects were randomised to one of three arms： RMT with aromatic oil（RA）, RMT without aromatic oil（RM） or standardised sham massage（SM）. In the study the subjects were exposed to a standardised stress situation followed by one of the study techniques and Holter electrocardiograms（ECGs） were recorded for 24 h.Main outcome measures： HRV parameters were calculated from linear（time and frequency domain） and nonlinear dynamics（symbolic dynamics, Poincare plot analysis） of the 24-h Holter ECG records.Results： Short-and long-term effects of massage on autonomic regulation differed significantly among the three groups. Immediately after an RMT session, stimulation of HRV was found in the groups RA and RM. The use of an aromatic oil produced greater short-term measurable changes in HRV compared with rhythmic massage alone, but after 24 h the effect was no longer distinguishable from the RM group.The lowest stimulation of HRV parameters was measured in the SM group.Conclusion： RMT causes specific and marked stimulation of the autonomic nervous system. Use of a medicinal aromatic oil had only a temporary effect on HRV, indicating that the RM causes the most relevant long-term effect. The effect is relatively specific, as the physiological effects seen in the group of subjects who received only SM were considerably less pronounced.

关键词： Sham massage Well-being Mood Alertness Relaxation Stress Heart rate variability Randomised controlled trial

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Detection of Cytokine Expression Patterns in the Peripheral Blood of Patients with Acute Leukemia by Antibody Microarray Analysis

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2014年第2期34卷 176-180页

作者：李青李梅吴耀辉朱晓健曾辰邹萍陈智超 Institute of hematology Union Hospital Tongji Medical College Huazhong University of Science and Technology Department of Pediatric Hematology Union Hospital Fujian Medical University

The cytokines of acute leukemia （AL） patients have certain expression patterns, forming a complex network involved in diagnosis, progression, and prognosis. We collected the serum of different AL patients before and after complete remission （CR） for detection of cytokines by using an antibody chip. The expression patterns of cytokines were determined by using bioinformatics computational analysis. The results showed that there were significant differences in the cytokine expression patterns between AL patients and normal controls, as well as between acute myeloid leukemia （AML） and acute lymphoblastic leukemia （ALL）. In confirmatory test, ELISA revealed the expression of uPAR in AL. Moreover, the bioinformatic analysis showed that the differentially expressed cytokines among the AL groups were involved in different biological behaviors and were closely related with the development of the disease. It was concluded that the cytokine expression pattern of AL patients is significantly different from that of healthy volunteers. Also, differences of cytokine expression patterns exist between AML and ALL, and between before and after CR in the same subtype of AL, which holds important clinical significance for revealing disease progression.

关键词： cytokine microarray acute leukemia expression patterns bioinformatics

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Preclinical evaluation of cyclophosphamide and fludarabine combined with CD19 CAR-T in the treatment of B-cell hematologic malignancies in vivo

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Oncology Research 2024年第6期32卷 1109-1118页

作者： ZHIGANG XIA MENGYAO TIAN YUCAI CHENG WENFANG YI ZEFAN DU TIANWEN LI YUCHEN WEN LINDI LI YONG LIU CHUN CHEN pediatric hematology Laboratory Division of Hematology/OncologyDepartment of PediatricsThe Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhen518107China Scientific Research Center The Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhen518107China

Background:Chimeric antigen receptor T(CAR-T)cell therapy has achieved marked therapeutic success in ameliorating hematological malignancies.However,there is an extant void in the clinical guidelines concerning the most effective chemotherapy regimen prior to chimeric antigen receptor T(CAR-T)cell therapy,as well as the optimal timing for CAR-T cell infusion post-chemotherapy.Materials and Methods:We employed cell-derived tumor xenograft(CDX)murine models to delineate the optimal pre-conditioning chemotherapy regimen and timing for CAR-T cell treatment.Furthermore,transcriptome sequencing was implemented to identify the therapeutic targets and elucidate the underlying mechanisms governing the treatment regimen.Results:Our preclinical in vivo evaluation determined that a combination of cyclophosphamide and fludarabine,followed by the infusion of CD19 CAR-T cells five days subsequent to the chemotherapy,exerts the most efficacious therapeutic effect in B-cell hematological malignancies.Concurrently,RNA-seq data indicated that the therapeutic efficacy predominantly perturbs tumor cell metabolism,primarily through the inhibition of key mitochondrial targets,such as C-Jun Kinase enzyme(C-JUN).Conclusion:In summary,the present study offers critical clinical guidance and serves as an authoritative reference for the deployment of CD19 CAR-T cell therapy in the treatment of B-cell hematological malignancies.

关键词： CD19 CAR-T B-cell hematologic malignancies Metabolism In vivo

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Asparaginase-associated pancreatitis in chemotherapytreated pediatric patients:a five-year retrospective study

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World Journal of Emergency Medicine 2022年第4期13卷 313-321页

作者： Chen-xi Liu Yun-yu Zhang Qiu-shi Yang Shu-hong Shen Jing Chen Yan-jing Tang Chang-cheng Chen Zhuo Wang Bi-ru Li Juan Qian Ying Wang Wen-ting Hu Bo-tao Ning Department of Pediatric Hematology and Oncology Shanghai Children’s Medical CenterSchool of MedicineShanghai Jiao Tong UniversityShanghai 200127China department of pediatric Intensive Care Unit Shanghai Children’s Medical CenterSchool of MedicineShanghai Jiao Tong UniversityShanghai 200127China

Asparaginase(Asp)represents a key agent in induction remission for acute lymphoblastic leukemia(ALL)and certain subtypes of non-Hodgkin lymphoma(NHL).By catalyzing the hydrolysis of extracellular asparagine,thus depleting the level of plasma asparagine necessary for the growth of leukemic lymphoblasts,Asp can inhibit leukemic lymphoblast protein synthesis and lead to subsequent apoptosis with little myelosuppression.[1]This will achieve anti-leukemia efficacy,and promote the remission of leukemia.[2]A previous study showed that an Asp-containing regimen could significantly increase the event-free survival rate(71%vs.31%).[3]A previous study showed that those who completed the Asp regimen had a higher 5-year event-free survival rate(90%)than those who were unable to tolerate toxicity and quitted the treatment(73%).[4]

关键词： regimen acute pancreatitis

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