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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 ***,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 *** 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 ***,transcriptome sequencing was implemented to identify the therapeutic targets and elucidate the underlying mechanisms governing the treatment ***: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 ***,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

Diabetic cardiomyopathy:Importance of direct evidence to support the roles of NOD-like receptor protein 3 inflammasome and pyroptosis

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World Journal of Diabetes 2024年第8期15卷 1659-1662页

作者： Lu Cai Yi Tan Md Shahidul Islam Michael Horowitz Kupper A Wintergerst Pediatric Research Institute Departments of PediatricsRadiation OncologyPharmacology and ToxicologyUniversity of LouisvilleWendy Novak Diabetes InstituteNorton Children’s HospitalLouisvilleKY 40202United States department of Biochemistry School of Life SciencesUniversity of KwaZulu-NatalDurban 4000KwaZulu-NatalSouth Africa department of Medicine University of AdelaideAdelaide 5005Australia Pediatric Research Institute Division of EndocrinologyDepartment of PediatricsWendy Novak Diabetes InstituteNorton Children’s HospitalUniversity of LouisvilleLouisvilleKY 40202United States

Recently,the roles of pyroptosis,a form of cell death induced by activated NODlike receptor protein 3(NLRP3)inflammasome,in the pathogenesis of diabetic cardiomyopathy(DCM)have been extensively ***,most studies have focused mainly on whether diabetes increases the NLRP3 inflammasome and associated pyroptosis in the heart of type 1 or type 2 diabetic rodent models,and whether various medications and natural products prevent the development of DCM,associated with decreased levels of cardiac NLRP3 inflammasome and *** direct link of NLRP3 inflammasome and associated pyroptosis to the pathogenesis of DCM remains unclear based on the limited evidence derived from the available studies,with the approaches of NLRP3 gene silencing or pharmaceutical application of NLRP3 specific *** thus emphasize the requirement for more systematic studies that are designed to provide direct evidence to support the link,given that several studies have provided both direct and indirect evidence under specific *** editorial emphasizes that the current investigation should be circumspect in its conclusion,i.e.,not overemphasizing its role in the pathogenesis of DCM with the fact of only significantly increased expression or activation of NLRP3 inflammasome and pyroptosis in the heart of diabetic rodent *** clear-cut evidence-based causative roles of NLRP3 inflammasome and pyroptosis in the pathogenesis of DCM can help to develop effective and safe medications for the clinical management of DCM,targeting these biomarkers.

关键词： Diabetic cardiomyopathy Nucleotide oligomerization domain NOD-like receptor protein 3 inflammasome Cardiac cell death Pyroptosis

Simultaneous type III congenital esophageal atresia and patent ductus arteriosus in a low-weight patient: A case report

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World Journal of Clinical Cases 2024年第3期12卷 560-564页

作者： Yong-Yu Ma Jun-Ru Chen Shi-Wu Yang Shu-Yu Wang Xin Cao Jun Wu Faculty of pediatrics Children’s Hospital Affiliated to Kunming Medical UniversityKunming 650103Yunnan ProvinceChina department of Cardiothoracic Surgery Kunming Children’s HospitalKunming 650103Yunnan ProvinceChina

BACKGROUND We report a low-birth-weight child(1.8 kg)with neonatal type III congenital esophageal atresia(CEA)combined with symptomatic patent ductus arteriosus(PDA).After comprehensive evaluation,esophageal anastomosis was performed on postnatal day 11 after excluding surgical contraindications,and arterial catheter ligation was performed at the same *** surgery for CEA combined with PDA has not been clearly reported in the *** SUMMARY We report a 6-day-old female child with type III CEA and *** patient presented with foam at the mouth after birth,cough and shortness of breath after *** another hospital,she was considered to have neonatal pneumonia,neonatal jaundice and congenital heart disease and transferred to our *** iodine oil radiography of the esophagus and echocardiography we con-firmed diagnosis of CEA and *** diameter of the PDA was 8 mm,with obvious left to right *** performed right rear extrapleural orificium fistula ligation and esophageal anastomosis,and ligation of PDA via left axilla straight incision after 5 d of *** operations were successful,and the incision healed after 12 d,and the patient was *** re-examined the patient 1 mo after *** did not vomit when she ate rice *** angiography showed no stricture of the anastomotic *** patient weighed 3.2 *** For CEA patients with multiple risk factors,comprehensive,timely and accurate diagnosis and evaluation,and early treatment may improve prognosis.

关键词： Congenital esophageal atresia Patent ductus arteriosus Low weight One-stage operation Case report

Development of international guidelines by Tuina practitioners for specific acupoints of paediatrics Tuina(2022 version)

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Journal of Traditional Chinese Medicine 2024年第5期44卷 1044-1051页

作者： LAN Xiaoxue SUN Yanan WENG Zhiwen WANG Yue ZHANG Ying LIANG Yuanwen GU Sirui ZHOU Rong CHEN Qianji JIA Baolin BO Han WANG Fangying HE Qiang ZHANG Jie TAN Jiang YE Xingzhu WANG Xiyou YU Changhe CHEN Hong department of Tuina and Pain Management the First Clinical DepartmentBeijing University of Chinese Medicine department of Traditional Chinese Medicine Xuanwu HospitalCapital Medical University department of Tuina and Pain Management Dongzhimen Hospital of Beijing University of Chinese Medicine department of Encephalopathy Beijing Huairou Hospital of Traditional Chinese Medicine Yungang Community Health Service Center China Aerospace Science & Industry Corporation of 731 Hospital department of pediatrics China-Japan Friendship Clinical SchoolBeijing University of Chinese Medicine department of pediatrics the Second Clinical Medical College of Beijing University of Chinese Medicine Shenzhen Luohu Hospital of Traditional Chinese Medicine department of Chinese Medicine Raffles Medical Group department of Traditional Chinese Medicine Beiing Children's HospitalCapital Medicine UniversityNational Center for Children's Health Anzhen Community Health Service Center L. Ac. Ancient Healing Center Frederick department of Tuina and Pain Management Dongzhimen HospitalBeijing University of Chinese Medicine

OBJECTIVE: To establish a standardized framework encompassing the precise locations, manipulations,functions and indications of specific acupoints in the field of paediatric Tuina. METHODS: The development of consensus involved three distinct stages. Initially, a list of paediatric Tuina specific acupoints was compiled based on an extensive literature review, which was subsequently supplemented through expert interviews. In the second stage, the Delphi method was employed to assess the significance of acupoint locations, manipulations, functions, and indications. In situations where the questionnaire survey failed to yield agreement or when the experts held reservations, the nominal group approach was utilized during the expert consensus meeting. The final version of the technical standardized material was ultimately determined during an expert consensus conference. After undergoing external peer review and evaluation, the completed draft was prepared for public dissemination RESULTS: The comprehensive list identified a total of 66 specific acupoints. The location and manipulation questionnaire consisted of 156 items based on the literature database, while the function and indication questionnaire contained 116 items. Two rounds of Delphi surveys were conducted for the location and manipulation category, and another two rounds of Delphi surveys were conducted for the function and indication category. During the experts consensus meeting The panel of experts conducted in-depth discussions on 61 questions, resulting in the formulation of technical guidelines for the locations, manipulations, functions, and indications of 64 paediatric Tuina acupoints. Subsequently, the research team compiled and edited the draft of the technical guidelines for acupoints of paediatric Tuina, which was finalized after external review and feedback. CONCLUSION: This study successfully established the recognized technical standards for practitioners of paediatric Tuina, thereby standardizi

关键词： Child Delphi technique Tuina acupoint guideline international paediatrics

Associations of Perchlorate,Nitrate,and Thiocyanate with Sex Hormones among Children:A Nationally Representative Cross-sectional Study in U.S.

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Biomedical and Environmental Sciences 2024年第6期37卷 666-671页

作者： Yiwen Wang Guodong Ding Peipei Hu Yongjun Zhang department of pediatrics Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghai 200092China MOE-Shanghai Key Laboratory of Children’s Environmental Health Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghai 200092China

Nitrates,thiocyanates,and perchlorates are ubiquitous in the environment and can be introduced to the public through various dietary and environmental ***,thiocyanates,and perchlorates mainly affect health via the sam... 详细信息

关键词： mechanism sectional perchlorate

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Human herpesvirus 7 meningitis in an adolescent with normal immune function:A case report

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World Journal of Clinical Cases 2024年第18期12卷 3636-3643页

作者： Yuan-Yuan Zhen Jing Yang Pei-Yuan Liao department of pediatrics Qilu Hospital of Shandong University(Qingdao)Qingdao 266035Shandong ProvinceChina

BACKGROUND Human herpesvirus type 7(HHV-7)is a less common herpes virus that usually causes mild,self-limiting ***,in recent years,there have been increasing reports of HHV-7 causing serious central nervous system infections,especially *** pathogenesis and clinical features of HHV-7 meningitis,particularly in adolescents with normal immune function,remain incompletely ***,the purpose of this report is to share a case of HHV-7 meningitis in an immunocompetent adolescent with a view to deepening our understanding of the *** SUMMARY A 12-year-old female was admitted with fever,headache,and vomiting.4 d before admission,the patient developed a fever without obvious induction,with a temperature up to 39.5℃,no convulsions,accompanied by chills,headaches,fatigue,and no muscle *** patient was treated with fever reduction,which could be reduced to 38℃;repeated high fever,accompanied by vomiting 7-8 times;and no abdominal pain or *** patient was diagnosed with"acute suppurative tonsillitis"in a local hospital,and the blood routine was generally *** patient was given symptomatic support treatment such as"ceftriaxone sodium"and antiemetic rehydration for 2 d,and his condition did not *** patient's physical examination showed pharyngeal congestion,bilateral tonsil grade I hypertrophy,regression of purulent secretions,and cervical *** B-ultrasound:Opacity of the vitreous body and edema of the optic disc in both *** coherence tomography examination showed that the macular fovea was generally normal in both eyes,with edema of the optic *** virus monitoring results:*** gave ganciclovir antiviral therapy,dexamethasone anti-inflammatory treatment,mannitol to reduce cranial pressure,omeprazole to protect gastrointestinal mucosa,and calcium and potassium *** This study reports a case of HHV-7 meningitis in an adolescent with normal immune ***

关键词： Human herpesvirus 7 meningitis Immune function Immune deficiency Central system infection Case report

Use of donepezil for neurocognitive recovery after brain injury in adult and pediatric populations:a scoping review

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Neural Regeneration Research 2024年第8期19卷 1686-1695页

作者： Avery L.Miller Nathan K.Evanson J.Michael Taylor University of Cincinnati College of Medicine CincinnatiOHUSA department of pediatrics University of CincinnatiCincinnatiOHUSA department of Neurology and Rehabilitation Medicine University of CincinnatiCincinnatiOHUSA Division of Pediatric Rehabilitation Medicine Cincinnati Children’s Hospital Medical CenterCincinnatiOHUSA Division of Neurology Cincinnati Children’s Hospital Medical CenterCincinnatiOHUSA

There are few pharmacologic options for the treatment of cognitive deficits associated with traumatic brain injury in pediatric *** inhibitors such as donepezil have been evaluated in adult patients after traumatic brain injury,but relatively less is known about the effect in pediatric *** goal of this review is to identify knowledge gaps in the efficacy and safety of acetylcholinesterase inhibito rs as a potential a djuvant treatment fo r neurocognitive decline in pediatric patients with traumatic brain *** queried PubMed to identify literature published from database inception thro ugh June 2023 desc ribing the use of donepezil in young adult traumatic brain injury and pediatric patients with predefined *** on preselected search criteria,340 unique papers we re selected for title and abstra ct ***-two reco rds were reviewed in full after eliminating preclinical studies and pape rs outside the scope of the *** adult traumatic brain injury,we review results from 14 papers detailing 227 subjects where evidence suggests donepezil is well tole rated and shows both objective and patient-reported efficacy for reducing cognitive *** children,3 pape rs report on 5 children recovering from traumatic brain injury,showing limited *** additional 15 pediatric studies conducted in populations at risk for cognitive dysfunction provide a broader look at safety and efficacy in 210 patients in the pediatric age *** its promise for efficacy in adults with traumatic brain injury and tole rability in pediatric patients,we believe further study of donepezil for children and adolescents with traumatic brain injury is warranted.

关键词： acetylcholinesterase inhibitor adult cognition donepezil pediatrics traumatic brain injury

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Exposure to ephedrine attenuates Th1/Th2 imbalance underlying OVA-induced asthma through airway epithelial cell-derived exo-somal lnc-TRPM2-AS

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Chinese Journal of Natural Medicines 2024年第6期22卷 530-540页

作者： HU Yan WANG Mengqing XIE Jing JIAO Luojia DING Yi LUO Yinhe department of pediatrics The First Hospital of Hunan University of Chinese MedicineChangsha 410007China Hunan University of Chinese Medicine Changsha 410208China department of Rehabilitation Medical CollegeChangsha Civil Affairs Vocational and Technical CollegeChangsha 410004Hunan ProvinceChina Teaching and Research Office of Chinese and Western Combination Hunan University of Chinese MedicineChangsha 410208China

Although various anti-inflammatory medications,such as ephedrine,are employed to manage cough-variant asthma,their underlying mechanisms are yet to be fully *** studies suggest that exosomes derived from airway epithelial cells(AECs)contain components like messenger RNAs(mRNAs),micro-RNAs(miRNAs),and long noncoding RNA(lncRNA),which play roles in the occurrence and progression of airway *** study investigates the influence of AEC-derived exosomes on the efficacy of ephedrine in treating cough-variant *** established a mouse model of asthma and measured airway resist-ance and serum inflammatory cell ***-time polymerase chain reaction(RT-qPCR),Western blotting,and enzyme-linked im-munosorbent assay(ELISA)analyses were used to assess gene and protein expression *** were isolated and *** immunoprecipitation(RIP)and RNA pull-down assays were conducted to examine the interaction between hnRNPA2B1 and *** the ovalbumin(OVA)-challenged mouse model,ephedrine treatment reduced inflammatory responses,air-way resistance,and Th1/Th2 cell *** from OVA-treated AECs showed elevated levels of lnc-TRPM2-AS1,which were diminished following ephedrine *** exosomal lnc-TRPM2-AS1 mediated the Th1/Th2 imbalance in CD4^(+)T cells,with its packaging into exosomes being facilitated by *** study unveils a novel mechanism by which ephedrine ameli-orates OVA-induced CD4^(+)T cell imbalance by suppressing AEC-derived exosomal *** findings could provide a theoretical framework for using ephedrine in asthma treatment.

关键词： Asthma Ephedrine Exosomal lnc-TRPM2-AS1 Th1/Th2 imbalance HnRNPA2B1 Airway epithelial cells

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Frequency of Uveitis among Juvenile Idiopathic Arthritis Patients in a Tertiary Care Hospital of Bangladesh: A Retrospective Study

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Open Journal of Rheumatology and Autoimmune Diseases 2024年第3期14卷 144-156页

作者： Md. Asif Ali Mujammel Haque Kamrul Laila Mohammad Hafiz Al-Mamun Mohammed Mahbubul Islam Mohammad Imnul Islam Manik Kumar Talukder Pediatric Rheumatology Division Department of Pediatrics Bangabandhu Sheikh Mujib Medical University Dhaka Bangladesh

Background: Juvenile idiopathic arthritis (JIA) is the most frequently encountered pediatric rheumatologic disorder with an unknown etiology. At present there is no published data regarding the frequency of uveitis in patients with JIA in Bangladesh. This study aimed to observe the frequency of JIA-associated uveitis (JIAU) and distribution of uveitis among different sub-categories of JIA at the Pediatric Rheumatology division, both outdoor and indoor patients, department of pediatrics, Bangabandhu Sheikh Mujib Medical University (BSMMU) in Bangladesh. Methods: This was a retrospective study of 1784 JIA patients at the Pediatric Rheumatology division, BSMMU from July 2010 to March 2023. Results: Among the 1784 enrolled JIA patients, we observed that 0.73% of cases had uveitis. Here, 61.5% of JIAU cases were male. Most of the cases (92.3%) had bilateral uveitis and only 7.7% cases had unilateral uveitis. Among JIAU patients, the majority were Oligo JIA (53.8%), followed by ERA 30.8%, Poly JIA RF(−) 7.7% and Systemic JIA 7.7% cases respectively. This study also revealed that 15.4% of JIAU patients had ANA positivity and 23% had HLA B-27 positivity. Here we also found ocular complications associated with uveitis such as band keratopathy (23.1%), posterior synechiae (15.4%) and cataract (15.4%). Conclusions: In this study, we observed only 0.73% of patients of JIA had developed uveitis which is lower than the frequency observed in other European studies. This study also showed various ocular complications amongst JIA-associated uveitis patients which signifies the importance of adherence to periodic ophthalmological follow-up to prevent these ocular complications.

关键词： JIA Uveitis HLA-B27 ANA BSMMU