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The m^(6)A regulator KIAA1429 stabilizes RAB27B mRNA and promotes the progression of chronic myeloid leukemia and resistance to targeted therapy

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Genes & Diseases 2024年第2期11卷 993-1008页

作者： Fangyi Yao Fangmin Zhong Junyao Jiang Ying Cheng Shuai Xu Jing Liu Jin Lin Jing Zhang Shuqi Li Meiyong Li Yanmei Xu Bo Huang Xiaozhong Wang Jiangxi Province Key Laboratory of Laboratory medicine Jiangxi Provincial Clinical Research Center for Laboratory MedicineDepartment of Clinical LaboratoryThe Second Affiliated Hospital of Nanchang UniversityNanchangJiangxi 330006China

Chronic myeloid leukemia(CML)is a common adult *** the acute phase of the disease and the adverse effects of anti-cancer treatments can lead to a poor *** N6-methyladenine(m^(6)A)modification plays an important regulatory role in various physiological and pathological ***1429 is a known m^(6)A regulator,but the biological role of KIAA1429 in CML is *** this study,we observed that the m^(6)A levels and KIAA1429 expression were significantly up-regulated in patients with blast phase ***,KIAA1429 regulated the total level of RNA m^(6)A modification in the CML cells and promoted the malignant biological behaviors of CML cells,including proliferation,migration,and imatinib *** KIAA1429 in CML cells reduced the stability of RAB27B mRNA through the m^(6)A/YTHDF1 axis,consequently inhibiting CML proliferation and drug efflux,ultimately increasing the sensitivity of CML cells to ***,the knockdown of RAB27B also inhibited the proliferation and drug resistance of CML cells and promoted their ***,a recently developed anti-cancer agent,suppressed the expression of KIAA1429 and CML cell proliferation and promoted cell *** also inhibited the tumorigenesis of CML cells in *** combined use of rucaparib and imatinib enhanced the sensitivity of CML cells to *** study provides evidence that elevated KIAA1429 expression in the blast phase of CML enhances the stability of RAB27B mRNA through the m^(6)A/YTHDF1 axis to up-regulate RAB27B expression,thereby promoting CML *** exerts inhibitory effects on KIAA1429 expression and thus reduces CML progression.

关键词： Chronic myeloid leukemia KIAA1429 N6-methyladenine RAB27B Rucaparib YTHDF1

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Impact of lifestyle interventions on pathogenesis of nonalcoholic fatty liver disease

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World Journal of Gastroenterology 2024年第20期30卷 2633-2637页

作者： Wafaa Mohamed Ezzat department of Internal medicine Medical Research and Clinical Studies InstituteNational Research CenterGiza 12311Egypt

This editorial builds on the article titled“Establishment and validation of an adherence prediction system for lifestyle interventions in non-alcoholic fatty liver disease”by Zeng et *** carried out a critical examination of nonalcoholic fatty liver disease(NAFLD)pathogenesis and how lifestyle interventions could facilitate disease resolution,particularly highlighting that non-alcoholic steatohepatitis(NASH)is a severe form of *** discussion details that weight loss is a pivotal factor in disease outcomes:A 3%-5%reduction is enough for resolution in 50%of non-obese individuals,while a 7%-10%reduction achieves similar benefits in obese individuals,as demonstrated by magnetic resonance ***,the editorial underscores that such lifestyle changes are instrumental not only in resolving NAFLD but also in reversing hepatic steatosis and *** insights,derived from the research,emphasize the critical role of personalized lifestyle modifications in halting the progression of NAFLD to NASH and even reversing fibrosis,thus offering a template for effective patient management.

关键词： Nonalcoholic fatty liver disease Non-alcoholic steatohepatitis Diet Physical activity Life style

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NLRP3 activation in macrophages promotes acute intestinal injury in neonatal necrotizing enterocolitis

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World Journal of Pediatrics 2024年第2期20卷 153-164页

作者： Bo Shi Cheng-Jie Lyu Zhen-Kai Le Hao-Sen Ji Yi Xiao Yuan-Yuan Zhang Shou-Jiang Huang Lin-Jun Yu Qiang Shu Jin-Fa Tou Deng-Ming Lai department of Neonatal Surgery Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhou 310052China department of Pulmonology Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhou 310052China department of Thoracic and Cardiovascular Surgery Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhou 310052China

Background Macrophages are involved in various immune inflammatory disease *** study aimed to investigate the role and mechanism of macrophages in regulating acute intestinal injury in neonatal necrotizing enterocolitis(NEC).Methods CD68,nucleotide-binding oligomerization domain,leucine-rich repeat,and pyrin domain-containing 3(NLRP3),cysteine aspartate-specific protease-1(caspase-1),and interleukin-1β(IL-1β)in paraffin sections of intestinal tissues from NEC and control patients were detected with immunohistochemistry,immunofluorescence,and western *** pet milk,hypoxia and cold stimulation were used to establish a mouse(wild type and Nlrp3^(-/-))model of *** mouse macrophage(RAW 264.7)and rat intestinal epithelial cell-6 lines were also cultured followed by various ***,intestinal epithelial cell injuries,and IL-1β release were *** Compared to the gut“healthy”patients,the intestinal lamina propria of NEC patients had high macrophage infiltration and high NLRP3,caspase-1,and IL-1β ***,in vivo,the survival rate of Nlrp3^(-/-)NEC mice was dramatically improved,the proportion of intestinal macrophages was reduced,and intestinal injury was decreased compared to those of wild-type NEC ***3,caspase-1,and IL-1β derived from macrophages or supernatant from cocultures of macrophages and intestinal epithelial cells also caused intestinal epithelial cell *** Macrophage activation may be essential for NEC ***3/caspase-1/IL-1β cellular signals derived from macrophages may be the underlying mechanism of NEC development,and all these may be therapeutic targets for developing treatments for NEC.

关键词： Caspase-1 Interleukin-1β Macrophage Necrotizing enterocolitis NLRP3

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Role of mitochondrial dysfunction in kidney disease:Insights from the cGAS-STING signaling pathway

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Chinese Medical Journal 2024年第9期137卷 1044-1053页

作者： Lu Li Fei Liu Chunyue Feng Zhenjie Chen Nan Zhang Jianhua Mao department of Nephrology Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhouZhejiang 310052China department of Pediatric Intensive Care Unit Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhouZhejiang 310052China

Over the past decade,mitochondrial dysfunction has been investigated as a key contributor to acute and chronic kidney ***,the precise molecular mechanisms linking mitochondrial damage to kidney disease remain *** recent insights into the cyclic guanosine monophosphate-adenosine monophosphate(GMP-AMP)synthetase(cGAS)-stimulator of interferon gene(STING)signaling pathway have revealed its involvement in many renal *** of these findings is that mitochondrial DNA(mtDNA)induces inflammatory responses via the cGAS-STING ***,we provide an overview of the mechanisms underlying mtDNA release following mitochondrial damage,focusing specifically on the association between mtDNA release-activated cGAS-STING signaling and the development of kidney ***,we summarize the latest findings of cGAS-STING signaling pathway in cell,with a particular emphasis on its downstream signaling related to kidney *** review intends to enhance our understanding of the intricate relationship among the cGAS-STING pathway,kidney diseases,and mitochondrial dysfunction.

关键词： Mitochondrial dysfunction Mitochondrial DNA cGAS-STING pathway Kidney diseases Chronic kidney disease

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Influenza and pneumococcal vaccination coverage and associated factors in patients hospitalized with acute exacerbations of COPD in China:Findings from real-world data

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Chinese Medical Journal 2024年第10期137卷 1179-1189页

作者： Ruoxi He Xiaoxia Ren Ke Huang Jieping Lei Hongtao Niu Wei Li Fen Dong Baicun Li Ye Wang Ting Yang Chen Wang School of Population medicine and Public Health Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China department of Respiratory medicine National Key Clinical SpecialtyBranch of National Clinical Research Center for Respiratory DiseaseXiangya HospitalCentral South UniversityChangshaHunan 410008China department of Pulmonary and Critical Care medicine Center of Respiratory MedicineChina-Japan Friendship HospitalBeijing 100029China Institute of Respiratory medicine Chinese Academy of Medical SciencesBeijing 100029China National Center for Respiratory medicine Beijing 100029China National clinical research Center for Respiratory Diseases Beijing 100029China department of clinical research and Data Management Center of Respiratory MedicineChina-Japan Friendship HospitalBeijing 100029China

Background:Influenza and pneumococcal vaccination are a priority in patients with chronic obstructive pulmonary disease(COPD).However,limited information is available on vaccination coverage among patients with acute exacerbations of COPD(AECOPD)in *** study aimed to determine the rates and associated factors of influenza and pneumococcal vaccination in patients hospitalized with ***:Baseline data from a national,multicenter,hospital-based study that included adult inpatients with AECOPD between 2017 and 2021 were *** outcomes of interest were the influenza vaccination in the past year and the pneumococcal vaccination in the past 5 *** ensure national representativeness,rates were weighted according to the distribution of hospital levels and types enrolled in this *** Poisson regression based on mixed-effects models were used to determine the associated *** independent variables included the region and hospital features where the participants were located,sociodemographic characteristics(age,sex,rural/urban residence,education,etc.),and clinical indicators(COPD disease history,lung function parameters,comorbidities,etc.).The treatment profiles of the vaccinated and unvaccinated participants were ***:Of 6949 eligible participants,the weighted rates of influenza/pneumococcal,influenza,and pneumococcal vaccination were 2.72%(95%confidence interval[CI]:2.34%-3.10%),2.09%(95%CI:1.76%-2.43%),and 1.25%(95%CI:0.99%-1.51%),*** multivariable models,age≥60 years(60-69 years,odds ratio[OR]:1.90,95%CI:1.11-3.25;≥80 years,OR:2.00,95%CI:1.06-3.78),geographical regions(Northern China relative to Eastern China,OR:5.09,95%CI:1.96-13.21),urban residence(OR:1.69,95%CI:1.07-2.66),a higher education level(junior high school,OR:1.77,95%CI:1.21-2.58;senior high school or above,OR:2.61,95%CI:1.69-4.03),former smoking(OR:1.79,95%CI:1.15-2.79),and regular inhaled medication treatment(OR:3.28,95%CI:2.29-4.70)were

关键词： Chronic obstructive pulmonary disease Influenza Pneumococcal Vaccine AECOPD

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RNA modifications in cellular metabolism:implications for metabolism-targeted therapy and immunotherapy

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1565-1594页

作者： Wei-Wei Liu Si-Qing Zheng Tian Li Yun-Fei Fei Chen Wang Shuang Zhang Fei Wang Guan-Min Jiang Hao Wang department of Laboratory medicine The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiChina School of clinical medicine Shandong UniversityJinanChina Core Unit of National clinical research Center for Laboratory medicine HefeiChina Neurosurgical department The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiChina department of clinical Laboratory The Fifth Affiliated HospitalSun Yat-sen UniversityZhuhaiChina

Cellular metabolism is an intricate network satisfying bioenergetic and biosynthesis requirements of *** studies have been constantly making inroads in our understanding of pathophysiology,and inspiring development of *** a crucial component of epigenetics at post-transcription level,RNA modification significantly determines RNA fates,further affecting various biological processes and cellular *** be noted,immunometabolism defines the metabolic alterations occur on immune cells in different stages and immunological *** this review,we characterize the distribution features,modifying mechanisms and biological functions of 8 RNA modifications,including N6-methyladenosine(m6A),N6,2'-O-dimethyladenosine(m6Am),N1-methyladenosine(m1A),5-methylcytosine(m5C),N4-acetylcytosine(ac4C),N7-methylguanosine(m7G),Pseudouridine(V),adenosine-to-inosine(A-to-l)editing,which are relatively the most studied *** regulatory roles of these RNA modification on metabolism in diverse health and disease contexts are comprehensively described,categorized as glucose,lipid,amino acid,and mitochondrial *** we highlight the regulation of RNA modifications on immunometabolism,further influencing immune *** all,we provide a thorough discussion about clinical implications of RNA modification in metabolism-targeted therapy and immunotherapy,progression of RNA modification-targeted agents,and its potential in RNAtargeted ***,we give legitimate perspectives for future researches in this field from methodological requirements,mechanistic insights,to therapeutic applications.

关键词： metabolism targeted alterations

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Nutritional and lipid profile status of children with spinal muscular atrophy in China:A retrospective case-control study

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Chinese Medical Journal 2024年第10期137卷 1243-1245页

作者： Yijie Feng Jia Wei Mei Yao Jianing Jin Yiqin Cui Qi Long Fei Chen Yi Hong Dongming Zhou Jingjing Hu Xiao Chen Feng Gao Changzheng Yuan Shanshan Mao department of Neurology Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhouZhejiang 310052China department of Infection Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhouZhejiang 310052China department of Nutrition Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhouZhejiang 310052China Children’s Hospital Zhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhouZhejiang 310052China School of Public Health Zhejiang University School of MedicineHangzhouZhejiang 310012China Children’s Hospital School of Public HealthZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhouZhejiang 310052China

To the Editor:5q spinal muscular atrophy(5qSMA)is an autosomal recessive neuromuscular disorder caused by the lack of the survival motor neuron(SMN)protein encoded by the SMN1 gene,located at 5q11.2-q13.3.[1]The incidence is 1/10,000-1/6000 live births,and the mutation carrier rate in China is 1/42.[1]Spinal muscular atrophy(SMA)is mainly divided into four subtypes:SMA type I,II,III,and IV,based on the motor milestones ever *** I-III occur in children,[1]which often result in progressive muscular atrophy and weakness as well as multi-system dysfunction,including nutritional and metabolic issues.[2]Children with SMA may have hidden nutritional and lipid imbalances,despite normal body appearance and anthropometric measurements,making it difcult to detect early and intervene.

关键词： atrophy muscular children

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Characteristics and quality of clinical practice guidelines for diabetic kidney disease: a systematic review

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Journal of Traditional Chinese medicine 2024年第3期44卷 609-619页

作者： WANG Yuhuang ZHANG Le ZHANG Zhengshan YAO Zhi LI Xiyao SUN Luying LIAO Xing department of Nephropathy and Endocrine Dongzhimen HospitalBeijing University of Chinese Medicine Centre for Evidence-Based Chinese medicine Institute of Basic Research in Clinical MedicineChina Academy of Chinese Medical Sciences department of Endocrine One Zone Fangshan HospitalBeijing University of Chinese Medicine

OBJECTIVE: To assess the quality of clinical practice guidelines(CPGs) in the context of diabetic kidney disease(DKD) and determine whether any factors affect the quality. METHODS: We searched eight databases along with five international and national organizations to develop or archive guidelines from their inception to July 2023, with an additional search of ***. And the authoritative organizations related to nephrology. CPGs and consensus statements created using direct differential diagnosis or therapy for DKD were included without language restrictions. Their quality was evaluated by four reviewers using the Appraisal of Guidelines for research and Evaluation Ⅱ(AGREE Ⅱ) instrument. Along with the item and domain scores, the guideline was also allocated an overall quality score, which ranged from 1(lowest possible quality) to 7(highest possible quality). Moreover, an overall recommendation for use was also assigned(“recommended”, “recommended with modifications” or “not recommended”). RESULTS: A total of 16 CPGs were included, of which 14 were from Asia and the remaining two from Europe. These two CPGs were updated in the third version. Six CPGs were recommended for use because their primary domains scored in the medium or high category. Furthermore, five CPGs were recommended with modifications as the stakeholder involvement, applicability, and editorial independence domains were evaluated as low categories. In all domains, the lowest average score was for rigour of development(33%), followed by application(36%), and stakeholder involvement(51%). The highest average score was for scope and purpose(79%), followed by clarity of presentation(75%). None of the CPGs considered the patient's viewpoint, and six of 16 CPGs did not use any grading system to translate the evidence into recommendations. Additionally, only three of 16 CPGs shared search strategy, and eight of 16 CPGs did not declare a funding source. CONCLUSIONS: According to the AGREE II evaluation

关键词： appraisal of guidelines for research and evaluation II diabetic nephropathies practice guideline quality assessment systematic review

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Enterogenic Stenotrophomonas maltophilia migrates to the mammary gland to induce mastitis by activating the calcium-ROS-AMPK-mTOR-autophagy pathway

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Journal of Animal Science and Biotechnology 2024年第1期15卷 236-252页

作者： Zhaoqi He Caijun Zhao Yuhong He Zhuoyu Liu Guyue Fan Kun Zhu Yiqi Wang Naisheng Zhang Yunhe Fu Xiaoyu Hu department of clinical Veterinary medicine College of Veterinary MedicineJilin UniversityChangchun 130062Jilin ProvinceChina

Background Mastitis is an inflammatory disease of the mammary gland that has serious economic impacts on the dairy industry and endangers food *** previous study found that the body has a gut/rumen-mammary gland axis and that disturbance of the gut/rumen microbiota could result in‘gastroenterogenic mastitis'.However,the mechanism has not been fully ***,we found that long-term feeding of a high-concentrate diet induced mastitis in dairy cows,and the abundance of Stenotrophomonas maltophilia(***)was significantly increased in both the rumen and milk ***,we hypothesized that‘gastroenterogenic mastitis'can be induced by the migration of endogenous gut bacteria to the mammary ***,this study investigated the mechanism by which enterogenic *** induces *** First,*** was labelled with superfolder GFP and administered to mice via *** results showed that treatment with *** promoted the occurrence of mastitis and increased the permeability of the blood-milk barrier,leading to intestinal inflammation and intestinal ***,tracking of ingested *** revealed that *** could migrate from the gut to the mammary gland and induce ***,mammary gland transcriptome analysis showed that the calcium and AMPK signalling pathways were significantly upregulated in mice treated with ***,using mouse mammary epithelial cells(MMECs),we verified that *** induces mastitis through activation of the calcium-ROS-AMPK-mTOR-autophagy *** In conclusion,the results showed that enterogenic *** could migrate from the gut to the mammary gland via the gut-mammary axis and activate the calcium-ROS-AMPK-mTOR-autophagy pathway to induce *** the gut-mammary gland axis may also be an effective method to treat mastitis.

关键词： Calcium-ROS-AMPK-mTOR-autophagy pathway Gut-mammary axis Mastitis S.maltophilia

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Ketogenic diet therapy in children with epilepsy caused by SLC2A1 mutations:a single-center single-arm retrospective study

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World Journal of Pediatrics 2024年第5期20卷 517-524页

作者： Ying-Yan Wang Yun-Qing Zhou Li-Juan Luo Cui-Jin Wang Nan Shen Hao Li Ji-Wen Wang department of Neurology Shanghai Children’s Medical CenterSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina department of Infectious Diseases Shanghai Children’s Medical CenterSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina clinical research Ward Clinical Research CenterShanghai Children’s Medical CenterSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina

Background This retrospective study assessed the efficacy and safety of ketogenic diet therapies in children with epilepsy caused by SLC2A1 genetic mutations and glucose transporter type 1 deficiency *** Pediatric patients with epilepsy symptoms admitted to our medical center between January 2017 and October 2021 were included if they presented with an SLC2A1 genetic mutation on whole-exome *** analyzed the patients’convulsions and treatment with antiepileptic *** patients were followed up at different time periods after ketogenic diet *** Six patients with SLC2A1 mutations were included in this *** patients had seizures of different types and frequencies,and they took antiepileptic drugs to relieve their *** were then treated with a ketogenic diet for at least four *** analyzed epilepsy control rates at 1,2,3,6,and 12 months after ketogenic diet *** patients were seizure-free within a month of receiving the diet *** patients were followed up for six months,three were followed up for 12 months after the treatment,and there was no recurrence of epilepsy during this *** antiepileptic drug withdrawal,none of the patients experienced seizure relapse when receiving ketogenic diet treatment *** severe adverse events occurred during the *** Ketogenic diet therapy is very effective and safe for the treatment of epilepsy caused by SLC2A1 ***,patients with glucose transporter type 1 deficiency syndrome caused by SLC2A1 mutations should begin ketogenic diet treatment as soon as possible.

关键词： Epilepsy Glucose transporter type 1 Ketogenic diet SLC2A1

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