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Bronchoalveolar lavage fluid assessment facilitates precision medicine for lung cancer

Cancer Biology & Medicine 2024年第3期21卷 230-251页

作者： Hantao Zhang Dan Deng Shujun Li Jing Ren Wei Huang Dan Liu Weiya Wang Department of Pathology West China HospitalSichuan UniversityChengdu 610000China west china biobank West China HospitalSichuan UniversityChengdu 610000China Department of Respiratory and Critical Care Medicine Clinical Research Center for Respiratory DiseaseWest China HospitalSichuan UniversityChengdu 610000China

Lung cancer is the most common and fatal malignant disease worldwide and has the highest mortality rate among tumor-related causes of *** diagnosis and precision medicine can significantly improve the survival rate and prognosis of lung cancer *** present,the clinical diagnosis of lung cancer is challenging due to a lack of effective non-invasive detection methods and biomarkers,and treatment is primarily hindered by drug resistance and high tumor *** biopsy is a method for detecting circulating biomarkers in the blood and other body fluids containing genetic information from primary tumor *** lavage fluid(BALF)is a potential liquid biopsy medium that is rich in a variety of bioactive substances and cell *** contains information on the key characteristics of tumors,including the tumor subtype,gene mutation type,and tumor environment,thus BALF may be used as a diagnostic supplement to lung *** this review,the current research on BALF in the diagnosis,treatment,and prognosis of lung cancer is *** advantages and disadvantages of different components of BALF,including cells,cell-free DNA,extracellular vesicles,and micro RNA are *** particular,the great potential of extracellular vesicles in precision diagnosis and detection of drug-resistant for lung cancer is *** addition,the performance of liquid biopsies with different body fluid sources in lung cancer detection are compared to facilitate more selective studies involving BALF,thereby promoting the application of BALF for precision medicine in lung cancer patients in the future.

关键词： Lung cancer bronchoalveolar lavage fluid extracellular vesicles liquid biopsy precision medicine

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Tet methylcytosine dioxygenase 2(TET2)deficiency elicits EGFR-TKI(tyrosine kinase inhibitors)resistance in non-small cell lung cancer

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1706-1720页

作者： Jian Zhang Kejia Zhao Wenjing Zhou Ran Kang Shiyou Wei Yueli Shu Cheng Yu Yin Ku Yonghong Mao Hao Luo Juqin Yang Jiandong Mei Qiang Pu Senyi Deng Zhengyu Zha Gang Yuan Shensi Shen Yaohui Chen Lunxu Liu Department of Thoracic Surgery and Institute of Thoracic Oncology West China Hospital of Sichuan UniversityChengdu 610097China western china Collaborative Innovation Center for Early Diagnosis and Multidisciplinary Therapy of Lung Cancer Sichuan UniversityChengdu 610097China biobank of west china Hospital Sichuan UniversityChengdu 610041China

Despite epidermal growth factor receptor(EGFR)tyrosine kinase inhibitors(TKl)have shown remarkable efficacy in patients with EGFR-mutant non-small cell lung cancer(NSCLC),acquired resistance inevitably develops,limiting clinical *** found that TET2 was poly-ubiquitinated by E3 ligase CUL7^(FBXW11) and degraded in EGFR-TKI resistant NSCLC *** perturbationof TET2 rendered parental cells more tolerant to TKI ***2 was stabilized by MEK1 phosphorylation at Ser 1107,while MEK1 inactivation promoted its proteasome degradation by enhancing the recruitment of CUL7^(FBXW11),Loss of TET2 resulted in the upregulation of TNF/NF-kB signaling that confers the EGFR-TKI *** or pharmacological inhibition of NF-kB attenuate the TKI resistance both in vitro and in *** findings exemplified how a cell growth controlling kinase MEK1 leveraged the epigenetic homeostasis by regulating TET2,and demonstrated an alternative path of non-mutational acquired EGFR-TKI resistance modulated by TET2 ***,combined strategy exploiting EGFR-TKI and inhibitors of TET2/NF-κB axis holds therapeutic potential for treating NSCLC patients who suffered from this resistance.

关键词： TET2 TKI resistance

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Bidirectional relationship between type 2 diabetes mellitus and coronary artery disease:Prospective cohort study and genetic analyses

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Chinese Medical Journal 2024年第5期137卷 577-587页

作者： Wenqiang Zhang Li Zhang Chenghan Xiao Xueyao Wu Huijie Cui Chao Yang Peijing Yan Mingshuang Tang Yutong Wang Lin Chen Yunjie Liu Yanqiu Zou Ling Zhang Chunxia Yang Yuqin Yao Jiayuan Li Zhenmi Liu Xia Jiang Ben Zhang Department of Epidemiology and Biostatistics Institute of Systems EpidemiologyWest China-Peking Union Medical College C.C.Chen Institute of HealthWest China School of Public Health and West China Fourth HospitalSichuan UniversityChengduSichuan 610041China Department of Maternal Child and Adolescent HealthWest China School of Public Health and West China Fourth HospitalSichuan UniversityChengduSichuan 610041China Department of Iatrical Polymer Material and Artificial Apparatus School of Polymer Science and EngineeringSichuan UniversityChengduSichuan 610041China Department of Occupational and Environmental Health West China School of Public Health and West China Fourth HospitalSichuan UniversityChengduSichuan 610041China Department of Nutrition and Food Hygiene West China School of Public Health and West China Fourth HospitalSichuan UniversityChengduSichuan 610041China Department of Clinical Neuroscience Karolinska InstitutetStockholm 17177Sweden

Background:While type 2 diabetes mellitus(T2DM)is considered a putative causal risk factor for coronary artery disease(CAD),the intrinsic link underlying T2DM and CAD is not fully *** aimed to highlight the importance of integrated care targeting both diseases by investigating the phenotypic and genetic relationships between T2DM and ***:We evaluated phenotypic associations using data from the United Kingdom biobank(N=472,050).We investigated genetic relationships by leveraging genomic data conducted in European ancestry for T2DM,with and without adjustment for body mass index(BMI)(T2DM:N_(case)/N_(control)=74,124/824,006;T2DM adjusted for BMI[T2DM_(adj)BMI]:N_(case)/N_(control)=50,409/523,897)and for CAD(N_(case)/N_(control)=181,522/984,168).We performed additional analyses using genomic data conducted in multiancestry individuals for T2DM(N_(case)/N_(control)=180,834/1,159,055).Results:Observational analysis suggested a bidirectional relationship between T2DM and CAD(T2DM→CAD:hazard ratio[HR]=2.12,95%confidence interval[CI]:2.01–2.24;CAD→T2DM:HR=1.72,95%CI:1.63–1.81).A positive overall genetic correlation between T2DM and CAD was observed(r_(g)=0.39,P=1.43×10^(-75)),which was largely independent of BMI(T2DM_(adj)BMI–CAD:r_(g)=0.31,P=1.20×10^(–36)).This was corroborated by six local signals,among which 9p21.3 showed the strongest genetic ***-trait meta-analysis replicated 101 previously reported loci and discovered six novel pleiotropic *** randomization analysis supported a bidirectional causal relationship(T2DM→CAD:odds ratio[OR]=1.13,95%CI:1.11-1.16;CAD→T2DM:OR=1.12,95%CI:1.07-1.18),which was confirmed in multiancestry individuals(T2DM→CAD:OR=1.13,95%CI:1.10-1.16;CAD→T2DM:OR=1.08,95%CI:1.04-1.13).This bidirectional relationship was significantly mediated by systolic blood pressure and intake of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors,with mediation proportions of 54.1%(95%CI:24.9-83.4%)and 90.4%(95%CI

关键词： Type 2 diabetes mellitus Coronary artery disease Phenotypic association Genetic correlation Mendelian randomization

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Exploration of pathogenic microorganism within the small intestine of necrotizing enterocolitis

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World Journal of Pediatrics 2024年第2期20卷 165-172页

作者： Yan Wang Kun Jiang Qiao Xia Xia Kang Shan Wang Ji-Hong Yu Wen-Feng Ni Xiao-Qin Qi Ying-Na Zhang Jin-Bao Han Gang Liu Lei Hou Zhi-Chun Feng Liu-Ming Huang Clinical biobank Center Medical Innovation Research Division of ChinesePLA General HospitalBeijingChina Institute of Basic Medical Sciences Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Senior Department of Pediatrics The Seventh Medical Center of PLA General HospitalBeijing 100700China Department of Neurology The First Medical CenterChinese PLA General HospitalBeijing 100853China Department of Emergency Center National Center for Children's HealthBeijing Children's HospitalCapital Medical UniversityBeijing 100045China

Background Necrotizing enterocolitis(NEC)is the most common severe gastrointestinal emergency in *** designed this study to identify the pathogenic microorganisms of NEC in the microbiota of the small intestine of *** Using the 16S ribosomal DNA(rDNA)sequencing method,we compared and analyzed the structure and diversity of microbiotas in the intestinal feces of different groups of neonates:patients undergoing jejunostomy to treat NEC(NP group),neonates undergoing jejunostomy to treat other conditions(NN group),and neonates with NEC undergoing conservative treatment(NC group).We took intestinal feces and saliva samples from patients at different time *** The beta diversities of the NP,NN,and NC groups were all *** comparing the beta diversities between different time points in the NP group,we found similar beta diversities at time points El to E3 but significant differences between the E2-E3 and E4 time points:the abundances of Klebsiella and Enterococcus(Proteobacteria)were higher at the E1-E3 time points;the abundance of Escherichia-Shigella(Proteobacteria)increased at the E2 time point,and the abundance of Klebsiella decreased significantly,whereas that of Streptococcus increased significantly at the E4 time *** Our results suggest that the pathological changes of intestinal necrosis in the small intestine of infants with NEC are not directly caused by excessive proliferation of pathogenic bacteria in the small *** sources of microbiota in the small intestine of neonates,especially in premature infants,may be affected by multiple factors.

关键词： Microbiota Necrotizing enterocolitis-Small intestine 16S rDNA

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Amide proton transfer:A new magnetic resonance imaging technology toward individualized assessment

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Chinese Medical Journal 2024年第13期137卷 1614-1616页

作者： Yiming Meng Jing Sun Guirong Zhang Tao Yu Department of Central Laboratory Cancer Hospital of Dalian University of TechnologyLiaoning Cancer Hospital&InstituteShenyangLiaoning 110042China Department of biobank Cancer Hospital of Dalian University of TechnologyLiaoning Cancer Hospital&InstituteShenyangLiaoning 110042China Department of Medical Imaging Cancer Hospital of Dalian University of TechnologyLiaoning Cancer Hospital&InstituteLiaoning 110042China

To the Editor:The amide proton transfer(APT)magnetic resonance imaging(MRI)is an emerging molecular imaging method for detecting mobile proteins/peptides and the potential of hydrogen(pH)with enhanced detection sensitivity compared to direct measurement without external magnetic resonance contrast agents[Figure 1].Such changes may be potential markers for tumor aggressiveness,treatment efficacy,and overall ***,the utilization of APT can assist medical professionals in devising treatment regimens tailored to the individual needs of cancer patients,resulting in improved therapeutic outcomes.

关键词： Figure resonance transfer

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ALKBH5 gene polymorphisms and risk of neuroblastoma in Chinese children from Jiangsu Province

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Cancer Innovation 2024年第2期3卷 72-79页

作者： Qian Guan Xinxin Zhang Jiabin Liu Chunlei Zhou Jinhong Zhu Haiyan Wu Zhenjian Zhuo Jing He Department of Pediatric Surgery Guangzhou Institute of PediatricsGuangdong Provincial Key Laboratory of Research in Structural Birth Defect DiseaseGuangdong Provincial Clinical Research Center for Child HealthGuangzhou Women and Children's Medical CenterGuangzhou Medical UniversityGuangzhouGuangdongChina Department of Pathology Children's Hospital of Nanjing Medical UniversityNanjingJiangsuChina Department of Clinical Laboratory BiobankHarbin Medical University Cancer HospitalHarbinHeilongjiangChina Laboratory Animal Center School of Chemical Biology and BiotechnologyPeking University Shenzhen Graduate SchoolShenzhenGuangdongChina

Background:Neuroblastoma is one of the most common extracranial malignant solid tumors in *** homolog 5(ALKBH5)is an RNA N6-methyladenosine(m6A)demethylase that plays a critical role in tumorigenesis and *** assessed the association between single nucleotide polymorphisms(SNPs)in ALKBH5 and the risk of neuroblastoma in a case-control study including 402 patients and 473 non-cancer ***:Genotyping was determined by the TaqMan *** association between ALKBH5 polymorphisms(rs1378602 and rs8400)and the risk of neuroblastoma was evaluated using the odds ratio(OR)and 95%confidence interval(CI).Results:We found no strong association of ALKBH5 rs1378602 and rs8400 with neuroblastoma *** stratification analysis by age,sex,primary site,and clinical stage showed that the rs1378602 AG/AA genotype was associated with a lower risk of neuroblastoma in males(adjusted OR=0.58,95%CI=0.35–0.97,p=0.036)and children with retroperitoneal neuroblastoma(adjusted OR=0.58,95%CI=0.34–0.98,p=0.040).Conclusions:ALKBH5 SNPs do not seem to be associated with neuroblastoma *** studies are required to confirm this negative result and reveal the relationship between gene polymorphisms of the m6A modifier ALKBH5 and neuroblastoma.

关键词： ALKBH5 neuroblastoma polymorphism susceptibility

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A comparison of the effect of alendronate and You-Gui-Wan on osteoporosis in female rats with kidney-yang deficiency

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Traditional Medicine Research 2024年第6期9卷 31-41页

作者： Mei-Mei Wu Xing-Peng He Wan-Ting Wu Wen-Jie Lu Yan-Yang Mai Kun-Cai Xu Yao-Feng Zhi Hai-Xin Mo Jia-Di He Xin Zhang Peng-Fei Li Clinical Experimental Center Jiangmen Engineering Technology Research Center of Clinical Biobank and Translational ResearchJiangmen Central HospitalJiangmen 529030China Traumatic Orthopedics Baiyun Hospital of The First Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510470China Department of Intelligent Engineering Guiyang Institute of Information Science and TechnologyGuiyang 550025China

Background:In traditional Chinese medicine,You-Gui-Wan(YGW)is typically used to treat osteoporosis associated with kidney-yang ***,there have been few mechanistic studies on the effectiveness of kidney-yang deficiency-type osteoporosis with *** further clarify the role of YGW in the effect of osteoporosis with kidney-yang deficiency,the study analyzed the therapeutic advantages of YGW by comparing the therapeutic effects of YGW and alendronate(ALN)on osteoporosis with kidney-yang ***:SPF female SD rats were randomly divided into control,osteoporosis,osteoporosis with kidney-yang deficiency,osteoporosis with kidney-yang deficiency+YGW and osteoporosis with kidney-yang deficiency+ALN *** for the control group,osteoporosis was induced by the removal of bilateral *** 12 weeks,rats with osteoporosis in the kidney-yang deficiency group had kidney-yang deficiency syndrome triggered by hydrocortisone for 14 *** were treated with YGW or ALN for 12 *** weights of rats were ***-eosin staining staining was used to observe pathological changes in bone trabeculae,liver,spleen,and kidneys of *** of the growth plate cartilage of rats in different groups was observed by safranine-O *** expression of osteoclast key indices(ACP)and osteoblast key indices(ALP)in the bone tissue of rats in the different groups was observed by immunohistochemical *** expression of bone resorption-related indicators(TRAP and NXT-1),bone formation-related indicators(BALP,BGP,and P1NP),and major indicators of kidney-yang deficiency(ACTH,T3,T4,cAMP,and cGMP)were observed using an ELISA detection *** expression levels of the main indices of liver function(ALT and AST)were detected in different ***:The differences between the osteoporosis with kidney-yang deficiency group and osteoporosis group were that the weight of rats and the expression of ACTH,T3,T4,and cAMP decreased significantl

关键词： osteoporosis kidney-yang deficiency You-Gui-Wan alendronate

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Gut microbial interactions based on network construction and bacterial pairwise cultivation

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Science china(Life Sciences) 2024年第8期67卷 1751-1762页

作者： Min-Zhi Jiang Chang Liu Chang Xu He Jiang Yulin Wang Shuang-Jiang Liu State Key Laboratory of Microbial Technology Shandong UniversityQingdao 266000China State Key Laboratory of Microbial Resources and Environmental Microbiology Research Center(EMRC)Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China

Association networks are widely applied for the prediction of bacterial interactions in studies of human gut ***,the experimental validation of the predicted interactions is challenging due to the complexity of gut microbiomes and the limited number of cultivated *** this study,we addressed this challenge by integrating in vitro time series network(TSN)associations and cocultivation of TSN taxon *** samples were collected and used for cultivation and enrichment of gut microbiome on YCFA agar plates for 13 *** cells were harvested for DNA extraction and metagenomic sequencing.A total of 198 metagenome-assembled genomes(MAGs)were *** dynamics of bacteria growing on the YCFA agar were used to infer microbial association *** experimentally validate the interactions of taxon pairs in networks,we selected 24 and 19 bacterial strains from this study and from the previously established human gut microbial biobank,respectively,for pairwise *** co-culture experiments revealed that most of the interactions between taxa in networks were identified as neutralism(51.67%),followed by commensalism(21.67%),amensalism(18.33%),competition(5%)and exploitation(3.33%).Genome-centric analysis further revealed that the commensal gut bacteria(helpers and beneficiaries)might interact with each other via the exchanges of amino acids with high biosynthetic costs,short-chain fatty acids,and/or *** also validated 12 beneficiaries by adding 16 additives into the basic YCFA medium and found that the growth of 66.7%of these strains was significantly *** approach provides new insights into the gut microbiome complexity and microbial interactions in association *** work highlights that the positive relationships in gut microbial communities tend to be overestimated,and that amino acids,short-chain fatty acids,and vitamins are contributed to the positive relationships.

关键词： human gut microbiome gut microbial pairwise interaction co-culture association network microbial community

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Association of accelerometer-measured sleep duration and different intensities of physical activity with incident type 2 diabetes in a population-based cohort study

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Journal of Sport and Health Science 2024年第2期13卷 222-232页

作者： Xinyi Jin Yilin Chen Hongliang Feng Mingqing Zhou Joey W.Y.Chang Yaping Liu Alice Pik Shan Kong Xiao Tan Yun-Kwok Wing Yannis Yan Liang Jihui Zhang Guangdong Cardiovascular Institute Guangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesGuangzhou 510080China Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention Guangdong Cardiovascular InstituteGuangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhou 510080China School of Medicine South China University of TechnologyGuangzhou 510641China Center for Sleep and Circadian Medicine The Affiliated Brain Hospital of Guangzhou Medical UniversityGuangzhou 510180China The Second School of Clinical Medicine Southern Medical UniversityGuangzhou 510282China Guangdong Mental Health Center Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhou 510120China Li Chiu Kong Family Sleep Assessment Unit Department of PsychiatryFaculty of MedicineThe Chinese University of Hong KongHong Kong 999077China Department of Psychiatry Faculty of MedicineThe Chinese University of Hong KongHong Kong 999077China Department of Medicine and Therapeutics Faculty of MedicineThe Chinese University of Hong KongHong Kong 999077China Department of Medical Sciences Uppsala UniversityUppsala 75185Sweden Department of Big Data in Health Science Zhejiang University School of Public HealthHangzhou 310058China Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of china Guangzhou 510260China

Purpose:The aim of the current study was to investigate the association of accelerometer-measured sleep duration and different intensities of physical activity(PA)with the risk of incident type 2 diabetes in a population-based prospective cohort ***:Altogether,88,000 participants(mean age=62.2±7.9 years,mean±SD)were included from the UK *** duration(short:8 h/day)and PA of different intensities were measured using a wrist-won accelerometer over a 7-day period between 2013 and *** was classified according to the median or World Health Organization-recommendation:total volume of PA(high,low),moderate-to-vigorous PA(MVPA)(recommended,not recommended),and light-intensity PA(high,low).Incidence of type 2diabetes was ascertained using hospital records or death ***:During a median follow-up of 7.0 years,1615 incident type 2 diabetes cases were *** with normal sleep duration,short(hazard ratio(HR)=1.21,95%confidence interval(95%CI):1.03-1.41)but not long sleep duration(HR=1.01,95%CI:0.89-1.15)was associated with excessive type 2 diabetes *** increased risk among short sleepers seems to be protected against by *** with normal sleepers with high or recommended PA,short sleepers with low volume of PA(HR=1.81,95%CI:1.46-2.25),not recommended(below the World Health Organization-recommended level of)MVPA(HR=1.92,95%CI:1.55-2.36),or low light-intensity PA(HR=1.49,95%CI:1.13-1.90)had a higher risk of type 2 diabetes,while short sleepers with a high volume of PA(HR=1.14,95%CI:0.88-1.49),recommended MVPA(HR=1.02,95%CI:0.71-1.48),or high light-intensity PA(HR=1.14,95%CI:0.92-1.41)did ***:Accelerometer-measured short but not long sleep duration was associated with a higher risk of incident type 2 diabetes.A higher level of PA,regardless of intensity,potentially ameliorates this excessive risk.

关键词： Light physical activity Sleep duration Triaxial accelerometer Type 2 diabetes UK biobank

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Whole-genome sequencing identifies novel genes for autism in Chinese trios

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Science china Life Sciences 2024年

作者： Suhua Chang Jia Jia Liu Yilu Zhao Tao Pang Xiangyu Zheng Zhirui Song Anyi Zhang Xuping Gao Lingxue Luo Yanqing Guo Jing Liu Li Yang Lin Lu Peking University Sixth Hospital Peking University Institute of Mental HealthNHC Key Laboratory of Mental Health (Peking University)National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital) Chinese Academy of Medical Sciences Research Unit (No.2018RU006) Peking University School of Nursing Peking University Wuhan biobank National Institute on Drug Dependence Peking University

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with high genetic heritability but *** understanding its genetics requires whole-genome sequencing (WGS),but the ASD studies utilizing WGS data in Chinese population are *** this study,we present a WGS study for 334 individuals,including 112 ASD patients and their non-ASD *** identified 146 de novo variants in coding regions in 85 cases and 60 inherited variants in coding *** integrating these variants with an association model,we identified 33 potential risk genes (P<0.001) enriched in neuron and regulation related biological *** the well-known ASD genes (SCN2A,NF1,SHANK3,CHD8 etc.),several high confidence genes were highlighted by a series of functional analyses,including CTNND1,DGKZ,LRP1,DDN,ZNF483,NR4A2,SMAD6,INTS1,and MRPL12,with more supported evidence from GO enrichment,expression and network *** also integrated RNA-seq data to analyze the effect of the variants on the gene expression and found 12 genes in the individuals with the related variants had relatively biased *** further presented the clinical phenotypes of the proband carrying the risk genes in both our samples and Caucasian samples to show the effect of the risk genes on *** variants in noncoding regions,a total of 74 de novo variants and 30 inherited variants were predicted as pathogenic with high confidence,which were mapped to specific genes or regulatory *** number of de novo variants found in patient was significantly associated with the parents’ages at the birth of the child,and gender with *** also identified small de novo structural variants in ASD *** results in this study provided important evidence for understanding the genetic mechanism of ASD.

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