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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 leukemia.Both the acute phase of the disease and the adverse effects of anti-cancer treatments can lead to a poor prognosis.The N6-methyladenine(m^(6)A)modification plays an important regulatory role in various physiological and pathological processes.KIAA1429 is a known m^(6)A regulator,but the biological role of KIAA1429 in CML is unclear.In this study,we observed that the m^(6)A levels and KIAA1429 expression were significantly up-regulated in patients with blast phase CML.Notably,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 resistance.Inhibiting 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 imatinib.Moreover,the knockdown of RAB27B also inhibited the proliferation and drug resistance of CML cells and promoted their apoptosis.Rucaparib,a recently developed anti-cancer agent,suppressed the expression of KIAA1429 and CML cell proliferation and promoted cell apoptosis.Rucaparib also inhibited the tumorigenesis of CML cells in vivo.The combined use of rucaparib and imatinib enhanced the sensitivity of CML cells to imatinib.Our 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 progression.Rucaparib 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 short-term ambient air pollution exposure on the risk of severe COVID-19

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Journal of Environmental Sciences 2024年第1期135卷 610-618页

作者： Baihuan Feng Jiangshan Lian Fei Yu Dan Zhang Weizhen Chen QiWang Yifei Shen Guoliang Xie Ruonan Wang Yun Teng Bin Lou Shufa Zheng Yida Yang Yu Chen Department of laboratory medicine The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310000China Key laboratory of clinical In Vitro Diagnostic Techniques of Zhejiang Province Hangzhou 310000China Institute of laboratory medicine Zhejiang UniversityHangzhou 310000China Department of Infectious Diseases The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310000China State Key laboratory for Diagnosis and Treatment of Infectious Diseases National Clinical Research Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious Diseasesthe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310000China

Ecological studies suggested a link between air pollution and severe COVID-19 outcomes,while studies accounting for individual-level characteristics are limited.In the present study,we aimed to investigate the impact of short-term ambient air pollution exposure on disease severity among a cohort of 569 laboratory confirmed COVID-19 patients admitted to designated hospitals in Zhejiang province,China,from January 17 to March 3,2020,and elucidate the possible biological processes involved using transcriptomics.Compared with mild cases,severe cases had higher proportion of medical conditions as well as unfavorable results in most of the laboratory tests,and manifested higher air pollution exposure levels.Higher exposure to air pollutants was associated with increased risk of severe COVID-19 with odds ratio(OR)of 1.89(95%confidence interval(CI):1.01,3.53),2.35(95%CI:1.20,4.61),2.87(95%CI:1.68,4.91),and 2.01(95%CI:1.10,3.69)for PM_(2.5),PM_(10),NO_(2)and CO,respectively.OR for NO_(2)remained significant in two-pollutant models after adjusting for other pollutants.Transcriptional analysis showed 884 differentially expressed genes which mainly were enriched in virus clearance related biological processes between patients with high and low NO_(2)exposure levels,indicating that compromised immune response might be a potential underlying mechanistic pathway.These findings highlight the impact of shortterm air pollution exposure,particularly for NO_(2),on COVID-19 severity,and emphasize the significance in mitigating the COVID-19 burden of commitments to improve air quality.

关键词： Air pollution COVID-19 Severity Transcriptomics Immune response

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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 cells.Relevant studies have been constantly making inroads in our understanding of pathophysiology,and inspiring development of therapeutics.As a crucial component of epigenetics at post-transcription level,RNA modification significantly determines RNA fates,further affecting various biological processes and cellular phenotypes.To be noted,immunometabolism defines the metabolic alterations occur on immune cells in different stages and immunological contexts.In 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 types.Then 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 metabolism.And we highlight the regulation of RNA modifications on immunometabolism,further influencing immune responses.Above 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 therapeutics.Eventually,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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Pancreatic β-cell failure, clinical implications, and therapeutic strategies in type 2 diabetes

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中华医学杂志(英文版) 2024年第7期137卷 791-805页

作者： Cui Daxin Feng Xingrong Lei Siman Zhang Hongmei Hu Wanxin Yang Shanshan Yu Xiaoqian Su Zhiguang Molecular medicine Research center and Department of Endocrinology and Metabolism West China Hospital Sichuan University Chengdu Sichuan 610041 China State Key laboratory of Biotherapy clinical Translational Innovation center

Pancreatic β-cell failure due to a reduction in function and mass has been defined as a primary contributor to the progression of type 2 diabetes (T2D). Reserving insulin-producing β-cells and hence restoring insulin production are gaining attention in translational diabetes research, and β-cell replenishment has been the main focus for diabetes treatment. Significant findings in β-cell proliferation, transdifferentiation, pluripotent stem cell differentiation, and associated small molecules have served as promising strategies to regenerate β-cells. In this review, we summarize current knowledge on the mechanisms implicated in β-cell dynamic processes under physiological and diabetic conditions, in which genetic factors, age-related alterations, metabolic stresses, and compromised identity are critical factors contributing to β-cell failure in T2D. The article also focuses on recent advances in therapeutic strategies for diabetes treatment by promoting β-cell proliferation, inducing non-β-cell transdifferentiation, and reprograming stem cell differentiation. Although a significant challenge remains for each of these strategies, the recognition of the mechanisms responsible for β-cell development and mature endocrine cell plasticity and remarkable advances in the generation of exogenous β-cells from stem cells and single-cell studies pave the way for developing potential approaches to cure diabetes.

关键词： Pancreatic β-cell regeneration Diabetes Insulin Dedifferentiation Transdifferentiation Stem cell

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Sodium Sulfite as a Novel Hypoxia Revulsant Involved in Hypoxic Regulation in Escherichia coli

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Biomedical and Environmental Sciences 2024年第2期37卷 228-232页

作者： YE Qiao HUO Jia Nan LUO Yuan MEI Zhu Song FANG Long Mei GUO Bing Qian WANG Guang Yun laboratory of clinical medicine Air Force Medical CenterAir Force Medical UniversityBeijing 100142China

As a reducing salt,sodium sulfite could deprive oxygen in solution,which could mimic hypoxic stress in Caenorhabditis elegans.In this study,the wildtype Escherichia coli strain MG1655 was used to examine the inhibitio... 详细信息

关键词： hypoxic Sodium observing

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Distribution of Traditional Chinese medicine syndromes in diabetic kidney disease chronic kidney disease 1-5: a correlation study

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Journal of Traditional Chinese medicine 2024年第3期44卷 572-580页

作者： LI Shuang DUAN Shuwei DONG Zheyi QU Yilun LUO Yayong KE Jianghua WANG Conghui PENG Yangzhi ZHOU Xuefeng CHEN Xiangmei Department of Nephrology First Medical Center of Chinese PLA General HospitalNephrology Institute of the Chinese People's Liberation ArmyNational Key Laboratory of Kidney DiseasesNational Clinical Research Center for Kidney DiseasesBeijing Key Laboratory of Kidney Disease Research School of clinical medicine Guangdong Pharmaceutical University Basic Medical College Chengdu University of Traditional Chinese Medicine

OBJECTIVE: To analyze the distribution of Traditional Chinese medicine(TCM) syndromes in patients with diabetic kidney disease(DKD) and its related factors.METHODS: We enrolled 435 patients with DKD, who were not undergoing dialysis, admitted to the Department of Nephrology, First Medical center, Chinese PLA General Hospital from April 2020 to August 2021.Analysis of their TCM syndromes and related factors was carried out.RESULTS: The 435 patients included 109, 117, 86, and 123 chronic kidney disease(CKD) 1-2, CKD3, CKD4, and CKD5 cases, respectively. With the progression of CKD1-5, the proportion of Yin deficiency and dry heat syndrome,and that of Qi and Yin deficiency syndrome showed a downward trend, whereas the proportion of spleen-kidney Yang deficiency, blood deficiency, blood stasis, water stagnation, and phlegm turbidity syndromes showed an upward trend; the differences were statistically significant(P < 0.05). Multivariate logistic regression analysis showed that Yin deficiency and dry heat syndrome was positively correlated with hemoglobin [odds ratio(OR) =1.022, P = 0.005], albumin(OR = 1.058, P = 0.006), and estimated glomerular filtration rate(eGFR)(OR = 1.020,P < 0.001) but negatively correlated with male sex(OR =0.277, P = 0.004). Qi and Yin deficiency syndrome was positively correlated with albumin(OR = 1.056, P < 0.001)and eGFR(OR = 1.008, P = 0.022) but negatively correlated with age(OR = 0.977, P = 0.023). Liver-kidney Yin deficiency syndrome was positively correlated with age(OR = 1.028, P = 0.021) and glycosylated hemoglobin(OR = 1.223, P = 0.007) but negatively correlated with total cholesterol(OR = 0.792, P = 0.006).Spleen-kidney Yang deficiency syndrome was negatively correlated with hemoglobin(OR = 0.977, P < 0.001),albumin(OR = 0.891, P < 0.001), and eGFR(OR = 0.978,P < 0.001) but positively correlated with high density lipoprotein(OR = 3.376, P = 0.001). CONCLUSION: With CKD1-5 progression, TCM syndromes changed from Yin deficiency and dry heat syndrome to syndrome of deficiency of both

关键词： albumins correlation of data diabetic nephropathies glomerular filtration rate hemoglobins syndrome and complex

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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 Africa.The Omicron strain spread and mutated significantly fast.This 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

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Mechanism Exploration of Euphorbia fischeriana Steud. for Liver Cancer Based on Aspartic Acid Identification in Metabolomics

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Chinese Journal of Integrative medicine 2024年第6期30卷 507-514页

作者： ZHAO Jing TIAN Xin-chen ZHANG Jia-qi HUANG Chen SUN Yan QIAO Sen JIANG Shu-long clinical Medical laboratory center Jining First People’s HospitalJiningShandong Province272000China Cheeloo College of medicine Shandong UniversityJinan250000China

Objective:To investigate the anti-liver cancer effects and aspartic acid(Asp)-related action mechanism of Euphorbia fischeriana Steud.(LD).Methods:The mice model of liver cancer was established by injection of H22 cells.After 5 days,mice were randomly divided into model group,sorafenib group(20 mg/kg),LD high-dose(LDH,1.36 g/kg) group,LD medium-dose(LDM,0.68 g/kg) group,and LD low-dose(LDL,0.34 g/kg)group,10 mice each group.Drugs were intragastrically administered to the mice once daily for 10 days,respectively.Body weight,tumor size and tumor weight were recorded.Hepatic index was calculated.Pathological changes of liver cancer tissues were evaluated by hematoxylin and eosin staining and TUNEL staining.Liquid chromatography-mass spectrometer was used to analyze different metabolites between the model and LDH groups.Results:After LD treatment,tumor weight,tumor size and hepatic index were reduced compared with the model group.Necrocytosis and karyorrhexis of tumor cells were found.Moreover,61 differential metabolites(18 up-regulated,43 down-regulated) were affirmed and 20 pathways of KEGG(P<0.05) were gotten.In addition,Bel-7402,HepG2 and H22 cell viabilities were significantly increased after adding Asp into the medium.And then,the cell proliferation effect induced by Asp was ameliorated by LD.Conclusion:The anti-liver cancer efficacy of LD extract was validated in H22 mice model,and inhibition of Asp level might be the underlying mechanism.

关键词： liver cancer Euphorbia fischeriana Steud. aspartic acid metabolomics

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Association between body mass index and in vitro fertilization/intra-cytoplasmic sperm injection outcomes: An analysis of 15,124 normal ovarian responders in China

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中华医学杂志(英文版) 2024年第7期137卷 837-845页

作者： Zheng Danlei Wang Yuanyuan Chen Lixue Zeng Lin Li Rong Department of Obstetrics and Gynecology center for Reproductive medicine Peking University Third Hospital Beijing 100191 China Research center of clinical Epidemiology

Background: High body mass index (BMI) results in decreased fecundity, and women with high BMI have reduced rates of clinical pregnancy and live birth inin vitro fertilization/intra-cytoplasmic sperm injection (IVF/ICSI). Meanwhile, ovarian responses show great heterogeneity in patients with a high BMI. This study aimed to analyze the effects of a high BMI on IVF/ICSI outcomes in the Chinese female with normal ovarian response.Methods: We performed a retrospective cohort study comprising 15,124 patients from the medical record system of the Reproductive center of Peking University Third Hospital, with 3530 (23.3%) in the overweight group and 1380 (9.1%) in the obese group, who had a normal ovarian response (5-15 oocytes retrieved) and underwent fresh embryo transfer (ET) cycles from January 2017 to December 2018, followed by linked frozen-thawed embryo transfer (FET) cycles from January 2017 to December 2020. Cumulative live birth rate (CLBR) was used as the primary outcome. Furthermore, a generalized additive model was applied to visually illustrate the curvilinear relationship between BMI and the outcomes. We used a decision tree to identify the specific population where high BMI had the greatest effect on IVF/ICSI outcomes.Results: High BMI was associated with poor IVF/ICSI outcomes, both in cumulative cycles and in separate fresh ET or FET cycles. In cumulative cycles, compared with the normal weight group, obesity was correlated with a lower positive pregnancy test rate (adjusted odds ratio [aOR]: 0.809, 95% confidence interval [CI]: 0.682-0.960), lower clinical pregnancy rate (aOR: 0.766, 95% CI: 0.646-0.907), lower live birth rate (aOR: 0.706, 95% CI: 0.595-0.838), higher cesarean section rate (aOR: 2.066, 95% CI: 1.533-2.785), and higher rate of large for gestational age (aOR: 2.273, 95% CI: 1.547-3.341). In the generalized additive model, we found that CLBR declined with increasing BMI, with 24 kg/m2 as an inflection point. In the decision tree, BMI only made a difference in the population aged ≤34.5 yea

关键词： Obesity Body mass index In vitro fertilization Live birth Decision trees Normal ovarian response

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clinical relevance of distolingual roots and periodontal status in mandibular first molars: a cross-sectional study employing CBCT analysis

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第3期25卷 244-253页

作者： Feifei MAO Meng WANG Shuai ZHOU Yan ZHAO Jiaping HUANG Fengying YIN Haiping YANG Pei-hui DING Stomatology Hospital School of StomatologyZhejiang University School of MedicineZhejiang Provincial Clinical Research Center for Oral DiseasesKey Laboratory of Oral Biomedical Research of Zhejiang ProvinceCancer Center of Zhejiang UniversityHangzhou 310016China

Objectives:Distolingual root of the permanent mandibular first molar(PMFM-DLR)has been frequently reported,which may complicate the treatment of periodontitis.This study aimed to assess the morphological features of PMFM-DLR and investigate the correlation between the morphological features of PMFM-DLR and periodontal status in patients with Eastern Chinese ethnic background.Materials and methods:A total of 836 cone beam computed tomography(CBCT)images with 1497 mandibular first molars were analyzed to observe the prevalence of PMFM-DLR at the patients and tooth levels in Eastern China.Among them,complete periodontal charts were available for 69 Chinese patients with 103 teeth.Correlation and regression analyses were used to evaluate the correlation between the morphological features of DLR,bone loss,and periodontal clinical parameters,including clinical attachment loss(CAL),probing pocket depth(PPD),gingival recession(GR),and furcation involvement(FI).Results:The patient-level prevalence and tooth-level prevalence of DLR in mandibular first molars were 29.4%and 26.3%,respectively.Multiple linear regression analysis suggested that bone loss at the lingual site and CAL were negatively affected by the angle of separation between distolingual and mesial roots in the transverse section,while they were significantly influenced by age and the angle of separation between distobuccal and mesial roots in the coronal section.Conclusions:The prevalence of PMFM-DLR in Eastern China was relatively high in our cohort.The morphological features of DLR were correlated with the periodontal status of mandibular first molars.This study provides critical information on the morphological features of DLR for improved diagnosis and treatment options of mandibular molars with DLR.

关键词： Distolingual root Mandibular first molar Periodontal clinical parameter clinical attachment loss Cone beam computed tomography(CBCT)

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