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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

Accurate prediction of biliary atresia with an integrated model using MMP-7 levels and bile acids

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World Journal of Pediatrics 2024年第8期20卷 822-833页

作者： Yi-Jiang Han Shu-Qi Hu Jin-Hang Zhu Xiao Cai Deng-Ming Lai Bao-Hai Chen Kun Zhu Qiao Tong Xin-Rui Zhou Jia-Le Deng Jin-Fa Tou Zhuo Fang Li-Zhong Du Department of Neonatal Surgery Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhouChina Department of Data and Analytics WuXi Diagnostics Innovation Research InstituteShanghaiChina Department of Information center Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhouChina Department of Pathology Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhouChina Department of Neonatology Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhouChina

Background Biliary atresia(BA)is a rare fatal liver disease in children,and the aim of this study was to develop a method to diagnose BA *** We determined serum levels of matrix metalloproteinase-7(MMP-7),the results of 13 liver tests,and the levels of 20 bile acids,and integrated computational models were constructed to diagnose *** Our findings demonstrated that MMP-7 expression levels,as well as the results of four liver tests and levels of ten bile acids,were significantly different between 86 BA and 59 non-BA patients(Pprediction model revealed that MMP-7 levels alone had a higher predictive accuracy[area under the receiver operating characteristic curve(AUC)=0.966,95%confidence interval(CI):0.942,0.989]than liver test results and bile acid *** AUC was 0.890(95%CI 0.837,0.943)for liver test results and 0.825(95%CI 0.758,0.892)for bile acid ***,bile levels had a higher contribution to enhancing the predictive accuracy of MMP-7 levels(AUC=0.976,95%CI 0.953,1.000)than liver test *** AUC was 0.983(95%CI 0.962,1.000)for MMP-7 levels combined with liver test results and bile acid *** addition,we found that MMP-7 levels were highly correlated with gamma-glutamyl transferase levels and the liver fibrosis *** The innovative integrated models based on a large number of indicators provide a noninvasive and cost-effective approach for accurately diagnosing BA in children.

关键词： Bile aid.Biliary atresia Diagnosis Liver fibrosis Liver test MMP-7

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

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

Development and validation of a novel non-invasive test for diagnosing nonalcoholic fatty liver disease in Chinese children

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World Journal of Pediatrics 2024年第4期20卷 413-421页

作者： Zhe-Wen Qin Qian-Nan Ren Hong-Xi Zhang Ya-Ru Liu Ke Huang Wei Wu Guan-Ping Dong Yan Ni Jun-Fen Fu Division of Endocrinology National Clinical Research Center for Child HealthNational Children’s Regional Medical CenterThe Children’s HospitalDepartment of EndocrinologyNational Clinical Research Center for Child HealthNational Children’s Regional Medical CenterThe Children’s HospitalZhejiang University School of MedicineHangzhou310052China

With the exploding prevalence of obesity,many children are at risk of developing nonalcoholic fatty liver *** anthropometric and laboratory parameters,our study aimed to develop a model to quantitatively evaluate liver fat content(LFC)in children with *** A well-characterized cohort of 181 children between 5 and 16 years of age were recruited to the study in the Endocrinology Department as the derivation *** external validation cohort comprised 77 *** assessment of liver fat content was performed using proton magnetic resonance *** and laboratory metrics were measured in all subjects.B-ultrasound examination was carried out in the external validation *** Kruskal-Wallis test,Spearman bivariate correlation analyses,univariable linear regressions and multivariable linear regression were used to build the optimal predictive *** The model was based on indicators including alanine aminotransferase,homeostasis model assessment of insulin resistance,triglycerides,waist circumference and Tanner *** adjusted R^(2)of the model was 0.589,which presented high sensitivity and specificity both in internal[sensitivity of 0.824,specificity of 0.900,area under curve(AUC)of 0.900 with a 95%confidence interval:0.783–1.000]and external validation(sensitivity of 0.918 and specificity of 0.821,AUC of 0.901 with a 95%confidence interval:0.818–0.984).Conclusions Our model based on five clinical indicators was simple,non-invasive,and inexpensive;it had high sensitivity and specificity in predicting LFC in ***,it may be useful for identifying children with obesity who are at risk for developing nonalcoholic fatty liver disease.

关键词： Biochemical markers Children Magnetic resonance spectroscopy Nonalcoholic fatty liver disease Pediatric obesity

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

Effectiveness and Safety of Qishen Yiqi Dripping Pill in Patients with Acute Coronary Syndrome after Percutaneous Coronary Intervention:3-Year Results from a Multicentre Cohort Study

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Chinese Journal of Integrative medicine 2024年第10期30卷 877-885页

作者： BAI Rui-na GU Feng CHE Qian-zi ZHANG Xuan CAI Ya-jie XI Rui-xi ZHAO Yang GUO Ming DONG Guo-ju GAO Zhu-ye FU Chang-geng WANG Pei-li DU Jian-peng ZHANG Da-wu DUAN Wen-hui LI Li-zhi YANG Qiao-ning SHI Da-zhuo Department of Cardiovascular Xiyuan HospitalChina Academy of Chinese Medical SciencesBeijing100091China National clinical research center for Chinese medicine Cardiology Beijing100091China Department of Evidence-Based medicine Basic research Laboratory Institute of Basic Research in Clinical MedicineChina Academy of Chinese Medical SciencesBeijing100700China Department of Traditional Chinese medicine Beijing Shangdi HospitalBeijing100193China National Medical Products Administration Key Laboratory for Clinical Research and Evaluation of Traditional Chinese MedicineBeijing100091China

Objectives:To evaluate the effectiveness and safety of Qishen Yiqi Dripping Pill(QSYQ)in patients with acute coronary syndrome(ACS)after percutaneous coronary intervention(PCI).Methods:This multicentre prospective cohort study was conducted at 40 centers in *** with ACS after PCI entered either the QSYQ or Western medicine(WM)groups naturally based on whether they had received QSYQ before *** group received QSYQ(0.52 g,3 times a day for 12 months)in addition to *** primary endpoint included cardiac death,non-fatal myocardial infarction,and urgent *** secondary endpoint included rehospitalization due to ACS,heart failure,stroke,and other thrombotic *** of life was assessed by the Seattle Angina Questionnaire(SAQ).Results:A total of 936 patients completed follow-up of the primary endpoint from February 2012 to December ***,487 patients received QSYQ and *** a median follow-up of 566 days(inter quartile range,IQR,517–602),the primary endpoint occurred in 46(9.45%)and 65(14.48%)patients in QSYQ and WM groups respectively[adjusted hazard ratio(HR)0.60,95%confidence interval(CI)0.41–0.90;P=0.013].The secondary endpoint occurred in 61(12.53%)and 74(16.48%)patients in QSYQ and WM groups,respectively(adjusted HR 0.76,95%CI 0.53–1.09;P=0.136).In sensitivity analysis,the results still demonstrated that WM combined with QSYQ reduced the risk of the primary endpoint(HR 0.67,95%CI 0.46–0.98;P=0.039).Moreover,QSYQ improved the disease perception domain of the SAQ(P<0.05).Conclusions:In patients with ACS after PCI,QSYQ combined with WM reduced the incidence of the primary *** findings provide a promising option for managing ACS after PCI and suggest the potential treatment for reducing the risk of primary endpoint included cardiac death,non-fatal myocardial infarction,and urgent revascularization through intermittent administration of QSYQ.(Registration *** CTR-OOC-14005552).

关键词： Qishen Yiqi Dripping Pill acute coronary syndrome percutaneous coronary intervention primary and secondary endpoint

Monocyte to High-density Lipoprotein Cholesterol Ratio as a predictor of Nonalcoholic Fatty Liver Disease in Childhood Obesity

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Current Medical Science 2024年第4期44卷 692-697页

作者： Jun-feng ZHANG Feng-qing CAI Xiu-cai ZHANG Qing YE Department of Laboratory medicine Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhou310052China

Objective Inflammation is involved in the development and progression of nonalcoholic fatty liver disease(NAFLD).The monocyte to high-density lipoprotein cholesterol ratio(MHR)has emerged as a marker for various inflammation-related *** aim of the present study was to investigate the association between the MHR and NAFLD in a population with childhood *** Based on hepatic ultrasound,a total of 504 children with obesity(357 with NAFLD and 147 without NAFLD)were included in the *** correlation between the MHR and NAFLD risk factors was assessed by Pearson’s and Spearman’s *** stepwise logistic regression analyses were conducted to explore the association between the MHR and the risk of *** The MHR in patients with NAFLD was significantly greater than that in patients without NAFLD[0.52(0.44-0.67)versus 0.44(0.34-0.57),Ppredictor of NAFLD in childhood obesity patients,as were age(OR:1.205,95%CI:1.059-1.371;P=0.005],waist circumference[OR:1.037,95%CI:1.008-1.067;P=0.012],and alanine transaminase[OR:1.067,95%CI:1.045-1.089;Ppresent study showed that the MHR may serve as an available and useful indicator of NAFLD in individuals with childhood obesity.

关键词： nonalcoholic fatty liver disease obesity monocyte-to-high-density lipoprotein ratio marker

Coinfection of SARS-CoV-2 Omicron variant and other respiratory pathogens in children

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World Journal of Pediatrics 2024年第1期20卷 92-96页

作者： Wei Li Bing-Han Wang Bao-Hai Chen Yi Sun Lin Li Wen-Qing Xiang Ahmed Faisal Ali Lin-Xuan Su Hai-Yan Mao Hong-Qiang Shen Qiang Shu Department of clinical Laboratory Children's HospitalNational Clinical Research Center for Child HealthZhejiang University School of MedicineHangzhouChina School of Public Health Zhejiang University School of MedicineHangzhouChina Department of Information center Children's HospitalZhejiang University School of MedicineHangzhouChina Zhejiang Provincial center for Disease Control and prevention HangzhouChina Department of Thoracic&Cardiovascular Surgery Children's HospitalNational Clinical Research Center for Child HealthZhejiang University School of MedicineHangzhouChina

Since the outbreak of coronavirus disease 2019(COVID-19),the entire world has been affected by the epidemic[1,2].On November 9,2021,a variant of the novel coronavirus B.1.1.529 was detected for the first time from case samples in South *** Omicron strain spread and mutated significantly *** variant has the characteristics of escape immunity,which can induce relatively extreme disease and reduce the neutralization of antibodies in vaccinators,and is more likely to be reinfected[3,4].The clinical presentation of severe acute respiratory syndrome coronavirus 2(SARSCoV-2)in children has mild symptoms and a lower risk of hospitalization and death.

关键词： respiratory immunity acute