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Association between Non-high-density Lipoprotein Cholesterol to High-density Lipoprotein Cholesterol Ratio(NHHR)and Stroke among Adults in the USA:A Cross-Sectional NHANES Study

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Biomedical and Environmental Sciences 2025年第1期38卷 37-46页

作者： Haixia Ma Huaqiu Chen Peichang Wang Department of Clinical Laboratory Xuanwu HospitalNational Clinical Research Center for Geriatric DiseasesCapital Medical UniversityBeijing 100053China National Clinical Research center for geriatric Disorders Xuanwu HospitalCapital Medical UniversityBeijing 100053China

Objective The relationship between non-high-density lipoprotein(NHDL)cholesterol to high-density lipoprotein cholesterol(HDL-C)ratio(NHHR)and stoke remains *** study aimed to evaluate the association between the adult NHHR and stroke occurrence in the United States of America(USA).Methods To clarify the relationship between the NHHR and stroke risk,this study used a multivariable logistic regression model and a restricted cubic spline(RCS)model to investigate the association between the NHHR and stroke,and data from the National Health and Nutrition Examination Survey(NHANES)from 2005 to *** and sensitivity analyses were conducted to test the robustness of the *** This study included 29,928 adult participants,of which 1,165 participants had a history of *** regression analysis of variables demonstrated a positive association between NHHR and stroke(OR 1.24,95%CI:1.03-1.50,P=0.026).Compared with the lowest reference group of NHHR,participants in the second,third,and fourth quartile had a significantly increased risk of stroke after full adjustments(OR:1.35,95%CI:1.08-1.69)(OR:1.83,95%CI:1.42-2.36)(OR:2.04,95%CI:1.50-2.79).In the total population,a nonlinear dose-response relationship was observed between the NHHR and stroke risk(P non-linearity=0.002).This association remained significant in several subgroup *** investigation of the NHHR may enhance our understanding of stroke prevention and *** Our findings suggest a positive correlation between the NHHR and an increased prevalence of stroke,potentially serving as a novel predictive factor for *** intervention and management of the NHHR may effectively mitigate stroke *** studies are required to validate this association and further explore the underlying biological mechanisms.

关键词： NHHR Stroke NHANES Cross-sectional study

Timing of biomarker changes preceding Alzheimer's disease:for diagnosis,treatment or prevention?

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Science China(Life Sciences) 2025年第2期68卷 575-577页

作者： Meina Quan Innovation center for Neurological Disorders and Department of Neurology Xuanwu HospitalCapital Medical UniversityBeijing 100053China National Medical center for Neurological Diseases and National Clinical Research center for geriatric Diseases Beijing 100053China center of Alzheimer’s Disease Beijing Institute of Brain DisordersCollaborative Innovation Center for Brain DisordersBeijing 100053China

The pathophysiological and behavioural features of Alzheimer’s disease(AD)have been extensively investigated in transgenic mouse models,including the temporal sequence of each pathophysiological change and behavioural abnormality,a summary of which was recently presented by our team in this Journal(Li et al.,2023).Nevertheless,studying such features and timings directly in human patients before symptoms occur is challenging.

关键词： prevention Alzheimer diagnosis

Metabolic dysfunction-associated steatotic liver disease and type 2 diabetes:A dual threat to cardiac dysfunction progression

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World Journal of Cardiology 2025年第1期17卷 118-120页

作者： Wei Wang Charlie Cooper Chronic Disease and Health Management Research center Geriatric Hospital of Nanjing Medical UniversityNanjing 210024Jiangsu ProvinceChina

Metabolic dysfunction-associated steatotic liver disease(MASLD),particularly in patients with type 2 diabetes mellitus(T2DM),is increasingly recognized as a multi-system disease that affects both hepatic and cardiovascular *** study explores the association between MASLD-related liver fibrosis and cardiac dysfunction,focusing on how liver fibrosis contributes to cardiac remodeling and *** et al’s research highlights the strong correlation between liver fibrosis and changes in left ventricular mass,left atrial dimensions,and systolic and diastolic function in diabetic ***,the study suggests a protective role of sex-hormone binding protein against cardiac *** findings underline the importance of early detection of liver fibrosis using noninvasive markers like fibrosis-4 index and nonalcoholic fatty liver disease fibrosis scores,which may offer dual protection for both liver and heart health in T2DM ***,this study calls for further research into the shared pathogenic mechanisms,including inflammation and fibrosis pathways,between the liver and *** advocates for the integration of liver fibrosis screening into cardiovascular risk management,urging clinicians to adopt a more holistic approach in treating patients with MASLD and *** research has broad implications for preventing cardiovascular complications and improving outcomes in this highrisk population.

关键词： Metabolic dysfunction-associated steatotic liver disease Type 2 diabetes Cardiac dysfunction Left ventricular mass Sex-hormone binding protein Fibrosis-4 index scores

Approved delivery strategies for biopharmaceuticals

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Chinese Chemical Letters 2025年第2期36卷 69-79页

作者： Makhloufi Zoulikha Zhongjian Chen Jun Wu Wei He School of Pharmacy China Pharmaceutical University Shanghai Skin Disease Hospital Tongji University School of Medicine Department of geriatric Cardiology Jiangsu Provincial Key Laboratory of Geriatrics The First Affiliated Hospital of Nanjing Medical University

In recent years, biopharmaceuticals have witnessed remarkable advancements, transforming the landscape of therapeutic interventions. Biopharmaceuticals encompassing therapeutics generated through cutting-edge biotechnological methods have shown promising therapeutic outcomes. However, their clinical success hinges significantly on overcoming drug delivery challenges related to stability, intracellular delivery, immunogenicity, and pharmacokinetic properties. Herein, we provide an overview of various marketed macromolecules, including nucleic acids, and immunotherapeutic agents such as cytokines and monoclonal antibodies, as well as other therapeutic peptides/proteins like enzymes, hormones, and coagulation factors. Our primary focus is on elucidating the delivery challenges associated with these macromolecules and highlighting the pivotal role played by drug delivery platforms in the development of currently marketed products, offering valuable insights for both scientific research and the pharmaceutical industry.

关键词： Biopharmaceuticals Drug delivery Monoclonal antibodies Nucleic acids Proteins

Circadian nutrition:is meal timing an elixir for fatigue?

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Science Bulletin 2025年第3期70卷 309-312页

作者： Zhihui Zhang Lu Yan Jonas T.Treebak Min-Dian Li Department of Cardiovascular medicine Center for Circadian Metabolism and Cardiovascular DiseaseSouthwest HospitalArmy Medical UniversityChongqing 400038China Ministry of Education(MOE)Key Laboratory of geriatric Cardiovascular and Cerebrovascular Disease Chongqing 400038China Novo Nordisk Foundation center for Basic Metabolic Research Faculty of Health and Medical SciencesUniversity of CopenhagenCopenhagen 2200Denmark

Fatigue is increasingly prevalent in industrialized societies,highlighting an urgent need for effective clinical and lifestyle *** manifests as reduced muscle endurance,strength and a persistent sensation of exhaustio... 详细信息

关键词： fatigue strength sensation

Unraveling brain aging through the lens of oral microbiota

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Neural Regeneration Research 2025年第7期20卷 1930-1943页

作者： Qinchao Hu Si Wang Weiqi Zhang Jing Qu Guang-Hui Liu State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijingChina Hospital of Stomatology Guanghua School of StomatologyGuangdong Provincial Key Laboratory of StomatologySun Yat-sen UniversityGuangzhouGuangdong ProvinceChina Advanced Innovation center for Human Brain Protection and National Clinical Research center for geriatric Disorders Xuanwu HospitalCapital Medical UniversityBeijingChina Aging Translational medicine center International Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical UniversityBeijingChina CAS Key Laboratory of Genomic and Precision medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijingChina University of Chinese Academy of Sciences BeijingChina Institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijingChina Aging Biomarker Consortium BeijingChina State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijingChina Beijing Institute for Stem Cell and Regenerative medicine BeijingChina

The oral cavity is a complex physiological community encompassing a wide range of *** of oral microbiota can lead to various oral infectious diseases,such as periodontitis and tooth decay,and even affect systemic health,including brain aging and neurodegenerative *** studies have highlighted how oral microbes might be involved in brain aging and neurodegeneration,indicating potential avenues for intervention *** this review,we summarize clinical evidence demonstrating a link between oral microbes/oral infectious diseases and brain aging/neurodegenerative diseases,and dissect potential mechanisms by which oral microbes contribute to brain aging and *** also highlight advances in therapeutic development grounded in the realm of oral microbes,with the goal of advancing brain health and promoting healthy aging.

关键词： Alzheimer's disease brain aging multiple sclerosis neurodegeneration neurodegenerative diseases oral microbiota Parkinson's disease periodontitis bacteria Porphyromonas gingivalis

Enhancing m^(6)A modification in the motor cortex facilitates corticospinal tract remodeling after spinal cord injury

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Neural Regeneration Research 2025年第6期20卷 1749-1763页

作者： Tian Qin Yuxin Jin Yiming Qin Feifei Yuan Hongbin Lu Jianzhong Hu Yong Cao Chengjun Li Department of Spine Surgery and Orthopedics Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina Key Laboratory of Organ Injury Aging and Regenerative Medicine of Hunan ProvinceChangshaHunan ProvinceChina National Clinical Research center for geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina Department of Sports medicine Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina

Spinal cord injury typically causes corticospinal tract disruption. Although the disrupted corticospinal tract can self-regenerate to a certain degree, the underlying mechanism of this process is still unclear. N6-methyladenosine(m^(6)A) modifications are the most common form of epigenetic regulation at the RNA level and play an essential role in biological processes. However, whether m^(6)A modifications participate in corticospinal tract regeneration after spinal cord injury remains unknown. We found that expression of methyltransferase 14 protein(METTL14) in the locomotor cortex was high after spinal cord injury and accompanied by elevated m^(6)A levels. Knockdown of Mettl14 in the locomotor cortex was not favorable for corticospinal tract regeneration and neurological recovery after spinal cord injury. Through bioinformatics analysis and methylated RNA immunoprecipitation-quantitative polymerase chain reaction, we found that METTL14 regulated Trib2 expression in an m^(6)A-regulated manner, thereby activating the mitogen-activated protein kinase pathway and promoting corticospinal tract regeneration. Finally, we administered syringin, a stabilizer of METTL14, using molecular docking. Results confirmed that syringin can promote corticospinal tract regeneration and facilitate neurological recovery by stabilizing METTL14. Findings from this study reveal that m^(6)A modification is involved in the regulation of corticospinal tract regeneration after spinal cord injury.

关键词： corticospinal tract remodeling epigenetic regulations locomotor cortex m^(6)A modification methyltransferase 14 protein(METTL14) mitogen-activated protein kinase neural regeneration spinal cord injury syringin TRIB2

Rat models of frozen shoulder:Classification and evaluation

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Animal Models and Experimental medicine 2025年第1期8卷 92-101页

作者： Hezirui Gu Wenqing Xie Hengzhen Li Shuguang Liu Yusheng Li Department of Orthopedics Xiangya HospitalCentral South UniversityChangshaChina Xiangya School of medicine Central South UniversityChangshaChina National Clinical Research center for geriatric Disorders Xiangya HospitalCentral South UniversityChangshaChina Department of Joint Surgery Honghui HospitalXi'an Jiaotong UniversityXi'anChina

Frozen shoulder(FS),also known as adhesive capsulitis,is a condition that causes contraction and stiffness of the shoulder joint *** main symptoms are per-sistent shoulder pain and a limited range of motion in all *** symp-toms and poor prognosis affect people's physical health and quality of ***,the specific mechanisms of FS remain unclear,and there is variability in treatment methods and their ***,the early symptoms of FS are difficult to distinguish from those of other shoulder diseases,complicating early diagnosis and ***,it is necessary to develop and utilize animal models to under-stand the pathogenesis of FS and to explore treatment strategies,providing insights into the prevention and treatment of human *** paper reviews the rat models available for FS research,including external immobilization models,surgical internal immobilization models,injection modeling models,and endocrine modeling *** introduces the basic procedures for these models and compares and analyzes the advantages,disadvantages,and applicability of each modeling ***,our paper summarizes the common methods for evaluating FS rat models.

关键词： endocrine modeling injection rat model surgical internal immobilization

Comprehensive molecular characterization to predict immunotherapy response in advanced biliary tract cancer:a phase II trial of pembrolizumab

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Oncology Research 2025年第1期33卷 57-65页

作者： RYUL KIM JOO KYUNG PARK MINSUK KWON MINAE AN JUNG YONG HONG JOON OH PARK SUNG HEE LIM SEUNG TAE KIM Division of Hematology-Oncology Department of MedicineSamsung Medical CenterSungkyunkwan University School of MedicineSeoulKorea Division of Gastroenterology Department of MedicineSamsung Medical CenterSungkyunkwan University School of MedicineSeoulKorea Department of Hematology-Oncology Ajou University School of MedicineSuwon-siGyeonggi-doKorea Samsung Advanced Institute of Health Science and Technology Sungkyunkwan University School of MedicineSeoulKorea

Background:Immune checkpoint inhibitors(ICIs)are effective in a subset of patients with metastatic solid ***,the patients who would benefit most from ICIs in biliary tract cancer(BTC)are still *** and methods:We molecularly characterized tissues and blood from 32 patients with metastatic BTC treated with the ICI pembrolizumab as second-line ***:All patients had microsatellite stable(MSS)type *** of the 32 patients achieved partial response(PR),with an objective response rate(ORR)of 9.4%(95%confidence interval[CI],2.0–25.2)and nine showed stable disease(SD),exhibiting a disease control rate(DCR)of 37.5%(95%CI,21.1–56.3).For the 31 patients who had access to PD-1 ligand 1(PD-L1)combined positive score(CPS)testing(cut-off value≥1%),the ORR was not different between those who had PD-L1-positive(PD-L1+;1/11,9.1%)and PDL1-(2/20,10.0%)tumors(p=1.000).The tumor mutational burden(TMB)of PD-L1+BTC was comparable to that of PD-L1-BTC(p=0.630).TMB and any exonic somatic mutations were also not predictive of pembrolizumab *** analysis of blood and tumor samples demonstrated a relatively high natural killer(NK)cell proportion in the peripheral blood before pembrolizumab treatment in patients who achieved tumor ***,the tumors of these patients presented high enrichment scores for NK cells,antitumor cytokines,and Th1 signatures,and a low enrichment score for cancer-associated ***:This study shows the molecular characteristics associated with the efficacy of pembrolizumab in BTC of the MSS type.

关键词： Pembrolizumab Whole-exome sequencing Whole-transcriptome sequencing Biliary tract cancer