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Associations of muscle mass,strength,and quality with all-cause mortality in China:a population-based cohort study

Chinese Medical Journal 2022年第11期135卷 1358-1368页

作者： Man Wu Yuxia Wei Jun Lv Yu Guo Pei Pei Jiachen Li Huaidong Du Ling Yang Yiping Chen Xiaohui Sun Hua Zhang Junshi Chen Zhengming Chen Canqing Yu Liming Li 无 Department of Epidemiology and Biostatistics School of Public HealthPeking UniversityBeijing 100191China Key Laboratory of Molecular Cardiovascular Sciences Ministry of EducationPeking UniversityBeijing 100191China Peking University Center for Public Health and Epidemic Preparedness&Responses Beijing 100191China National Coordinating Center of China Kadoorie biobank Chinese Academy of Medical SciencesBeijing 102308China Medical Research Council Population Health Research Unit the University of OxfordOxford OX37LFUK Clinical Trial Service Unit and Epidemiological Studies Unit(CTSU) Nuffield Department of Population HealthUniversity of OxfordOxford OX37LFUK NCDs Prevention and Control Department Qingdao CDCQingdaoShandong 266033China NHC Key Laboratory of Food Safety Risk Assessment China National Center for Food Safety Risk AssessmentBeijing 100022China. on behalf of the China Kadoorie biobank Collaborative Group

Background It remains unclear about the association of muscle mass,strength,and quality with death in the general Chinese population of diverse economical and geographical backgrounds.The present study aimed to comprehensively examine such associations across different regions in China.Methods Based on the China Kadoorie biobank study,the present study included 23,290 participants who were aged 38 to 88 years and had no prevalent cardiovascular diseases or cancer.Muscle mass and grip strength were measured using calibrated instruments.Arm muscle quality was defined as the ratio of grip strength to arm muscle mass.Low muscle mass,grip strength,and arm muscle quality were defined as the sex-specific lowest quintiles of muscle mass index,grip strength,and arm muscle quality,respectively.Cox proportional hazards models yielded hazard ratios(HRs)and 95%confidence intervals(CIs)for risks of all-cause mortality in relation to muscle mass,strength,and quality.Results During a median follow-up of 3.98 years,739 participants died.The HR(95%CI)of all-cause mortality risk was 1.28(1.08–1.51)for low appendicular muscle mass index,1.38(1.16–1.62)for low total muscle mass index,1.68(1.41–2.00)for low grip strength,and 1.41(1.20–1.66)for low arm muscle quality in models adjusted for sociodemographic characteristics,lifestyle factors,and medical histories.Conclusion Low muscle mass,grip strength,and arm muscle quality are all associated with short-term increased risks of mortality,indicating the importance of maintaining normal muscle mass,strength,and quality for general Chinese adults.

关键词： Muscle All-cause mortality Chinese Prospective Muscle mass Muscle strength Muscle quality

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Bronchoalveolar lavage fluid assessment facilitates precision medicine for lung cancer

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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 death.Early diagnosis and precision medicine can significantly improve the survival rate and prognosis of lung cancer patients.At 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 heterogeneity.Liquid biopsy is a method for detecting circulating biomarkers in the blood and other body fluids containing genetic information from primary tumor tissues.Bronchoalveolar lavage fluid(BALF)is a potential liquid biopsy medium that is rich in a variety of bioactive substances and cell components.BALF 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 biopsy.In this review,the current research on BALF in the diagnosis,treatment,and prognosis of lung cancer is summarized.The advantages and disadvantages of different components of BALF,including cells,cell-free DNA,extracellular vesicles,and micro RNA are introduced.In particular,the great potential of extracellular vesicles in precision diagnosis and detection of drug-resistant for lung cancer is highlighted.In 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 efficacy.We found that TET2 was poly-ubiquitinated by E3 ligase CUL7^(FBXW11) and degraded in EGFR-TKI resistant NSCLC ells.Genetic perturbationof TET2 rendered parental cells more tolerant to TKI treatment.TET2 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 resistance.Genetic or pharmacological inhibition of NF-kB attenuate the TKI resistance both in vitro and in vivo.Our 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 deficiency.Therefore,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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Amide proton transfer: A new magnetic resonance imaging technology toward individualized assessment

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中华医学杂志(英文版) 2024年第13期137卷 1614-1616页

作者： Meng Yiming Sun Jing Zhang Guirong Yu Tao Department of Central Laboratory Cancer Hospital of Dalian University of Technology Liaoning Cancer Hospital &amp Institute Shenyang Liaoning China Department of biobank Cancer Hospital of Dalian University of Technology Liaoning Cancer Hospital &amp Department of Medical Imaging Cancer Hospital of Dalian University of Technology Liaoning Cancer Hospital &amp Institute Liaoning China

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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 neonates.We designed this study to identify the pathogenic microorganisms of NEC in the microbiota of the small intestine of neonates.Methods 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 points.Results The beta diversities of the NP,NN,and NC groups were all similar.When 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 point.Conclusions 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 intestine.The 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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The evolution of cancer genomic medicine in Japan and the role of the National Cancer Center Japan

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Cancer Biology & Medicine 2024年第1期21卷 29-44页

作者： Teruhiko Yoshida Yasushi Yatabe Ken Kato Genichiro Ishii Akinobu Hamada Hiroyuki Mano Kuniko Sunami Noboru Yamamoto Takashi Kohno Department of Genetic Medicine and Services National Cancer Center HospitalTokyo 104-0045Japan Department of Diagnostic Pathology National Cancer Center HospitalTokyo 104-0045Japan Clinical Research Support Offce Clinical Research Coordinating SectionBiobank Translational Research Support SectionNational Cancer Center HospitalTokyo 104-0045Japan Department of Pathology and Clinical Laboratories National Cancer Center Hospital EastChiba 277-8577Japan Division of Molecular Pharmacology National Cancer Center Research InstituteTokyo 104-0045Japan National Cancer Center Research Institute Tokyo 104-0045Japan Department of Laboratory Medicine National Cancer Center HospitalTokyo 104-0045Japan Department of Experimental Therapeutics National Cancer Center HospitalTokyo 104-0045Japan Division of Genome Biology National Cancer Center Research InstituteTokyo 104-0045Japan

The journey to implement cancer genomic medicine(CGM)in oncology practice began in the 1980s,which is considered the dawn of genetic and genomic cancer research.At the time,a variety of activating oncogenic alterations and their functional significance were unveiled in cancer cells,which led to the development of molecular targeted therapies in the 2000s and beyond.Although CGM is still a relatively new discipline and it is difficult to predict to what extent CGM will benefit the diverse pool of cancer patients,the National Cancer Center(NCC)of Japan has already contributed considerably to CGM advancement for the conquest of cancer.Looking back at these past achievements of the NCC,we predict that the future of CGM will involve the following:1)A biobank of paired cancerous and non-cancerous tissues and cells from various cancer types and stages will be developed.The quantity and quality of these samples will be compatible with omics analyses.All biobank samples will be linked to longitudinal clinical information.2)New technologies,such as whole-genome sequencing and artificial intelligence,will be introduced and new bioresources for functional and pharmacologic analyses(e.g.,a patient-derived xenograft library)will be systematically deployed.3)Fast and bidirectional translational research(bench-to-bedside and bedside-to-bench)performed by basic researchers and clinical investigators,preferably working alongside each other at the same institution,will be implemented;4)Close collaborations between academia,industry,regulatory bodies,and funding agencies will be established.5)There will be an investment in the other branch of CGM,personalized preventive medicine,based on the individual's genetic predisposition to cancer.

关键词： Cancer genomic medicine biobank patient-derived xenograft multi-gene panel test whole genome sequencing

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Multimorbidity patterns and association with mortality in 0.5 million Chinese adults

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Chinese Medical Journal 2022年第6期135卷 648-657页

作者： Junning Fan Zhijia Sun Canqing Yu Yu Guo Pei Pei Ling Yang Yiping Chen Huaidong Du Dianjianyi Sun Yuanjie Pang Jun Zhang Simon Gilbert Daniel Avery Junshi Chen Zhengming Chen Jun Lyu Liming Li On Behalf of the China Kadoorie biobank Collaborative Group Department of Epidemiology and Biostatistics School of Public HealthPeking UniversityBeijing 100191China Peking University Center for Public Health and Epidemic Preparedness and Response Peking UniversityBeijing 100191China National Clinical Research Center of Cardiovascular Diseases National Center for Cardiovascular DiseasesFuwai HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China China Kadoorie biobank National Coordination Centre Chinese Academy of Medical SciencesBeijing 100730China Nuffield Department of Population Health Medical Research Council Population Health Research UnitUniversity of OxfordOxford OX37LFUnited Kingdom Nuffield Department of Population Health University of OxfordClinical Trial Service Unit and Epidemiological Studies Unit(CTSU)Oxford OX37LFUnited Kingdom Suzhou Center for Disease Control and Prevention SuzhouJiangsu 215004China China National Center for Food Safety Risk Assessment Beijing 100022China Key Laboratory of Molecular Cardiovascular Sciences Peking UniversityMinistry of EducationBeijing 100191China 不详

Background:Few studies have assessed the relationship between multimorbidity patterns and mortality risk in the Chinese population.We aimed to identify multimorbidity patterns and examined the associations of multimorbidity patterns and the number of chronic diseases with the risk of mortality among Chinese middle-aged and older adults.Methods:We used data from the China Kadoorie biobank and included 512,723 participants aged 30 to 79 years.Multimorbidity was defined as the presence of two or more of the 15 chronic diseases collected by self-report or physical examination at baseline.Multimorbidity patterns were identified using hierarchical cluster analysis.Cox regression was used to estimate the associations of multimorbidity patterns and the number of chronic diseases with all-cause and cause-specific mortality.Results:Overall,15.8%of participants had multimorbidity.The prevalence of multimorbidity increased with age and was higher in urban than rural participants.Four multimorbidity patterns were identified,including cardiometabolic multimorbidity(diabetes,coronary heart disease,stroke,and hypertension),respiratory multimorbidity(tuberculosis,asthma,and chronic obstructive pulmonary disease),gastrointestinal and hepatorenal multimorbidity(gallstone disease,chronic kidney disease,cirrhosis,peptic ulcer,and cancer),and mental and arthritis multimorbidity(neurasthenia,psychiatric disorder,and rheumatoid arthritis).During a median of 10.8 years of follow-up,49,371 deaths occurred.Compared with participants without multimorbidity,cardiometabolic multimorbidity(hazard ratios[HR]=2.20,95%confidence intervals[CI]:2.14-2.26)and respiratory multimorbidity(HR=2.13,95%CI:1.97-2.31)demonstrated relatively higher risks of mortality,followed by gastrointestinal and hepatorenal multimorbidity(HR=1.33,95%CI:1.22-1.46).The mortality risk increased by 36%(HR=1.36,95%CI:1.35-1.37)with every additional disease.Conclusion:Cardiometabolic multimorbidity and respiratory multimorbidity posed the highest threat on mortality risk and d

关键词： Multimorbidity Pattern Mortality Chinese

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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 children.AlkB homolog 5(ALKBH5)is an RNA N6-methyladenosine(m6A)demethylase that plays a critical role in tumorigenesis and development.We 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 controls.Methods:Genotyping was determined by the TaqMan method.The 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 risk.Further 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 risk.More 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 deficiency.However,there have been few mechanistic studies on the effectiveness of kidney-yang deficiency-type osteoporosis with YGW.To 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 deficiency.Methods: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 groups.Except for the control group,osteoporosis was induced by the removal of bilateral ovaries.After 12 weeks,rats with osteoporosis in the kidney-yang deficiency group had kidney-yang deficiency syndrome triggered by hydrocortisone for 14 days.Rats were treated with YGW or ALN for 12 weeks.The weights of rats were recorded.Hematoxylin-eosin staining staining was used to observe pathological changes in bone trabeculae,liver,spleen,and kidneys of rats.Depletion of the growth plate cartilage of rats in different groups was observed by safranine-O staining.The 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 staining.The 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 kit.The expression levels of the main indices of liver function(ALT and AST)were detected in different groups.Results: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 significantly,and the expression of cGMP increased in the os

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

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Genomic medicine in clinical practice:national genomic medicine program in Japan

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Cancer Biology & Medicine 2024年第1期21卷 4-9页

Cancer statistics in Japan Cancer is the most common cause of death in Japan based on Statistics 2021~1.Since statistics were first gathered,infectious diseases,such as tuberculosis,and cerebrovascular disease have been the main causes of death in Japan.Cancer surpassed cerebrovascular disease as the main cause of death in 1981,and the number of cancer deaths has increased.Approximately 38,000 people died of cancer in 2021.The National Cancer Center(NCC)reported that the 5-year survival rate for patients with cancer was improving(62%for males and 66.9%for females)in a population-based cancer registry.

关键词： Cancer cancer death

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