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Cognitive impairment in cerebral small vessel disease induced by hypertension

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Neural Regeneration research 2024年第7期19卷 1454-1462页

作者： Weipeng Wei Denglei Ma Lin Li Lan Zhang Department of Pharmacy Xuanwu Hospital of Capital Medical UniversityBeijingChina Beijing Geriatric Medical research center Beijing Engineering Research Center for Nervous System DrugsNational Center for Neurological DisordersNational Clinical Research Center for Geriatric DiseasesBeijingChina

Hypertension is a primary risk factor for the progression of cognitive impairment caused by cerebral small vessel disease,the most common cerebrovascular disease.Howeve r,the causal relationship between hypertension and cerebral small vessel disease remains unclear.Hypertension has substantial negative impacts on brain health and is recognized as a risk factor for cerebrovascular disease.Chronic hypertension and lifestyle factors are associated with risks for stro ke and dementia,and cerebral small vessel disease can cause dementia and stroke.Hypertension is the main driver of cerebral small vessel disease,which changes the structure and function of cerebral vessels via various mechanisms and leads to lacunar infarction,leukoaraiosis,white matter lesions,and intracerebral hemorrhage,ultimately res ulting in cognitive decline and demonstrating that the brain is the to rget organ of hypertension.This review updates our understanding of the pathogenesis of hypertensioninduced cerebral small vessel disease and the res ulting changes in brain structure and function and declines in cognitive ability.We also discuss drugs to treat cerebral small vessel disease and cognitive impairment.

关键词： blood-brain barrier cerebral small vessel disease cognitive impairment dementia endothelial dysfunction enlarged perivascular space hypertension lacunar infarction neuroinflammation treatment white matter high signal intensity

Incidence and Mortality of Cancers in Female Genital Organs—China,2022

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China CDC weekly 2024年第10期6卷 195-202,I0003,I0004页

作者： Kexin Sun Bingfeng Han Hongmei Zeng Shaoming Wang Li Li Ru Chen Rongshou Zheng Wenqiang Wei national Central Cancer Registry National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

Introduction:This study presented the incidence and mortality rates of cancers affecting the female genital organs in China,along with their trends spanning from 2010 to 2018.Methods:700 population-based cancer registries provided relevant cancer incidence and mortality data for the year 2018.Among these,106 registries had continuous monitoring data suitable for trend analysis from 2010 to 2018.We focused specifically on cancers affecting female genital organs(ICD10=C51-C54,C56)and projected their incidences and mortalities in China for 2022 based on data from 2018 and the trends observed from 2010 to 2018.Age-standardized incidence rate(ASIR)and mortality rate(ASMR)were calculated using Segi’s world standard population.Results:In 2022,there were an estimated 296,300 new cases and 104,900 deaths from female cancers in China.ASIRs for vulva(C51),vagina(C52),cervix uteri(C53),corpus uteri(C54),and ovary(C56)were 0.32,0.23,13.83,6.84,and 5.68 per 100,000 population.ASIRs for corpus uteri and ovary cancers were higher in urban areas.ASMRs for vulva,vagina,cervix,corpus uteri,and ovary cancers were 0.14,0.08,4.54,1.05,and 2.64 per 100,000 population,respectively.ASMR for ovarian cancer was higher in urban areas.ASIRs and ASMRs for most female genital organ cancers increased from 2010 to 2018,although the rate of increase for vulvar and cervical cancers in rural areas has slowed recently.Conclusions:Tailored cancer prevention and control programs specific to each region are necessary to address the growing disease burden.

关键词： ICD10 mortality organs

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 disease.Using anthropometric and laboratory parameters,our study aimed to develop a model to quantitatively evaluate liver fat content(LFC)in children with obesity.Methods 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 cohort.The external validation cohort comprised 77 children.The assessment of liver fat content was performed using proton magnetic resonance spectroscopy.Anthropometry and laboratory metrics were measured in all subjects.B-ultrasound examination was carried out in the external validation cohort.The Kruskal-Wallis test,Spearman bivariate correlation analyses,univariable linear regressions and multivariable linear regression were used to build the optimal predictive model.Results The model was based on indicators including alanine aminotransferase,homeostasis model assessment of insulin resistance,triglycerides,waist circumference and Tanner stage.The 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 children.Thus,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

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

Chromosome-level genome assembly of the Asian citrus psyllid,Diaphorina citri

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Insect Science 2024年第1期31卷 13-27页

作者： Shuang Lei Shi-Jiang Yu Qi Pan Li-Li Ding Si-Chen Li Lu-Yan Cheng Shu-Qi Wang Bing-Hai Lou Jun He Cui-Yun Lei Lin Cong Hao-Qiang Liu Xue-Feng Wang Chun Ran Citrus research Institute Southwest University/Chinese Academy of Agricultural SciencesNational Engineering Research Center for CitrusChongqingChina

Diaphorina citri is a global citrus pest.As a vector insect,it can transmit the causative agents of citrus huanglongbing,causing irreversible losses to the citrus industry.The acquisition of genomic information can provide a molecular genetic basis for effective control of D.citri.Here,the DNBSEQ™,Oxford Nanopore Technologies,and Hi-C technologies are applied to generate a high-quality chromosome-level genome of D.citri.The genome size of D.citri was 523.78 Mb with a scaffold N50 of 47.05 Mb distributed on 13 chromosomes.A total of 250.64 Mb(47.85%)repeat sequences and 24048 protein-coding genes were predicted.Genome resequencing of female and male individuals indicated that the sex chromosome system of D.citri is XO.Phylogenetic analysis demonstrated that D.citri and Pachypsylla venusta,which separated from their most recent common ancestor about 336.62 million years ago,were the most closely related.Additionally,we identified genes potentially involved in detoxification metabolism,pathogen transmission,and honeydew secretion for further investigation.The high-quality genome provides an important reference for developing effective management strategies of D.citri.

关键词： Asian citrus psyllid chromosome-level genome comparative genomics cytochrome P450 detoxification Huanglongbing

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

RARRES2 regulates lipid metabolic reprogramming to mediate the development of brain metastasis in triple negative breast cancer

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Military Medical research 2024年第1期11卷 34-49页

作者： Yi-Qun Li Fang-Zhou Sun Chun-Xiao Li Hong-Nan Mo Yan-Tong Zhou Dan Lv Jing-Tong Zhai Hai-Li Qian Fei Ma Department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China State Key Laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

Background Triple negative breast cancer(TNBC),the most aggressive subtype of breast cancer,is characterized by a high incidence of brain metastasis(BrM)and a poor prognosis.As the most lethal form of breast cancer,BrM remains a major clinical challenge due to its rising incidence and lack of effective treatment strategies.Recent evidence suggested a potential role of lipid metabolic reprogramming in breast cancer brain metastasis(BCBrM),but the underlying mechanisms are far from being fully elucidated.Methods Through analysis of BCBrM transcriptome data from mice and patients,and immunohistochemical validation on patient tissues,we identified and verified the specific down-regulation of retinoic acid receptor responder 2(RARRES2),a multifunctional adipokine and chemokine,in BrM of TNBC.We investigated the effect of aberrant RARRES2 expression of BrM in both in vitro and in vivo studies.Key signaling pathway components were evaluated using multi-omics approaches.Lipidomics were performed to elucidate the regulation of lipid metabolic reprogramming of RARRES2.Results We found that downregulation of RARRES2 is specifically associated with BCBrM,and that RARRES2 deficiency promoted BCBrM through lipid metabolic reprogramming.Mechanistically,reduced expression of RARRES2 in brain metastatic potential TNBC cells resulted in increased levels of glycerophospholipid and decreased levels of triacylglycerols by regulating phosphatase and tensin homologue(PTEN)-mammalian target of rapamycin(mTOR)-sterol regulatory element-binding protein 1(SREBP1)signaling pathway to facilitate the survival of breast cancer cells in the unique brain microenvironment.Conclusions Our work uncovers an essential role of RARRES2 in linking lipid metabolic reprogramming and the development of BrM.RARRES2-dependent metabolic functions may serve as potential biomarkers or therapeutic targets for BCBrM.

关键词： RARRES2 Lipid metabolic reprogramming Brain metastasis(BrM) Breast cancer

Relationship between mitochondrial respiratory dysfunction of blood mononuclear cells and heart failure severity

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Journal of Geriatric Cardiology 2024年第1期21卷 130-134页

作者： Viacheslav A.Korepanov Tariel A.Atabekov Tatiana Yu.Rebrova Roman E.Batalov Sergey A.Afanasiev Cardiology research Institute Tomsk National Research Medical CenterRussian Academy of SciencesTomskRussia

Chronic heart failure(CHF)is a clinical syndrome manifested by reduced pumping ability of the heart,increased pressure in heart chambers in both physical activity and at rest.The symptoms of this syndrome are dyspnea,undue fatigability,peripheral edema,which follow structural and functional changes of the myocardium.[1]The growing incidence of CHF,especially among elderly people,is an urgent problem for medicine in the vast majority of industrialized countries.For instance,in Russian Federation,CHF is diagnosed in about 7%of cardiovascular patients.At the same time,this indicator varies from 0.3%in young people(20-29 years old)to 70%in the older age group.[2,3].

关键词： severity instance pumping

Adaptive ultra-hypofractionated whole-pelvic radiotherapy in high-risk and very high-risk prostate cancer on 1.5-Tesla MR-Linac:Estimated delivered dose and early toxicity results

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Chronic Diseases and Translational Medicine 2024年第1期10卷 51-61页

作者： Linrui Gao Ran Wei Shirui Qin Yuan Tian Wenlong Xia Yongwen Song Shulian Wang Hui Fang Yu Tang Hao Jing Yueping Liu Yuan Tang Shunan Qi Bo Chen Yexiong Li Nianzeng Xing Ningning Lu Department of Radiation Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina GCP center/Clinical research center National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Department of Urology State Key Laboratory of Molecular OncologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

Background: Magnetic resonance(MR)-guided ultra-hypofractionated radiotherapy with whole-pelvic irradiation(UHF-WPRT)is a novel approach to radiotherapy for patients with high-risk(HR)and very high-risk(VHR)prostate cancer(PCa).However,the inherent complexity of adaptive UHF-WPRT might inevitably result in longer on-couch time.We aimed to estimate the delivered dose,study the feasibility and safety of adaptive UHF-WPRT on a 1.5-Tesla MR-Linac.Methods: Ten patients with clinical stage T3a-4N0-1M0-1c PCa,who consecutively received UHF-WPRT,were enrolled prospectively.The contours of the target and organ-at-risks on the position verification-MR(PV-MR),beam-on 3D-MR(Bn-MR),and post-MR(after radiotherapy delivery)were derived from the pre-MR data by deformable image registration.The physician then manually adjusted them,and dose recalculation was performed accordingly.GraphPad Prism 9(GraphPad Prism Software Inc.)was utilized for conducting statistical analyses.Results: In total,we collected 188 MR scans(50 pre-MR,50 PV-MR,44 Bn-MR,and 44 post-MR scans).With median 59 min,the mean prostate clinical target volume(CTV)-V_(100%)was 98.59%±2.74%,and the mean pelvic CTVp-V_(100%)relative percentages of all scans was 99.60%±1.18%.The median V29 Gy change in the rectal wall was−2%(−18%to 20%).With a median follow-up of 9 months,no patient had acute Common Terminology Criteria for Adverse Events(CTCAE)grade 2 or more severe genitourinary(GU)or gastrointestinal(GI)toxicities(0%).Conclusion: UHF-RT to the prostate and the whole pelvis with concomitant boost to positive nodes using an Adapt-To-Shape(ATS)workflow was technically feasible for patients with HR and VHR PCa,presenting only mild GU and GI toxicities.The estimated target dose during the beam-on phase was clinically acceptable based on the 3D-MR-based dosimetry analysis.Clinical trial registration Chinese Clinical Trial Registry ChiCTR2000033382.

关键词： dosimetry hypofractionation magnetic resonance imaging prostate cancer radiation dose radiotherapy