OBJECTIVES: To evaluate outcome and risk factors, particularly the (APATCHE II) score in elderly patients after admission to a geriatrics intensive care unit (ICU). Methods: A cross sectional study of patients ≥ 60 y...OBJECTIVES: To evaluate outcome and risk factors, particularly the (APATCHE II) score in elderly patients after admission to a geriatrics intensive care unit (ICU). Methods: A cross sectional study of patients ≥ 60 years admitted to the intensive care unit (ICU) of the Geriatrics department at Ain Shams University Hospital over 2 years period. We recorded age, sex, previous medical history, primary diagnosis, date of admission and discharge or death and APACHE II score on admission. Results: 202 patients admitted to the ICU were studied. The mean ICU mortality rates for these patients were (32, 5%), the mean APATCHE II score was (19.07). 27.3% of patients who died had hypokalemia and 43.2% had hyponatremia. Conclusion: ICU mortality rate are higher in elderly patients particularly with long ICU stay and hyponatremia.展开更多
Context: Exposure to burnout of staff involved with elderly patients is dependent on many factors either personal or linked to the professional environment. Social stress and systemic problems created particularly by ...Context: Exposure to burnout of staff involved with elderly patients is dependent on many factors either personal or linked to the professional environment. Social stress and systemic problems created particularly by difficulties inherent in the French hospital management system and the way people feel it, lead to a risk of burnout. One illustration of this is the rise in suicides at work. Quality of life at work, harassment and psycho-social risks are intimately linked. Affective factors, such as suffering for the medical carers in response to the distress of their patients aggravate the risk of burnout. Methods: We have evaluated these parameters using a self-filled questionnaire form sent to all staff and filled in by computer, anonymously, in 4 establishments, in December 2012 and over the first semester of 2013. After the three factors studied by the ProQOL scale of quality of life at work, to do with burnout, satisfaction compassion and fatigue compassion, 5 other questions were added, connected with a feeling of harassment and several social and demographic matters. Burnout risk was retained on reaching a threshold of 30 for this ProQOL scale item. Results: After multivariate analysis including the parameters of the Stamm scale, harassment and the socio-demographic factors studied, (age, sex, seniority, profession, and work departments) 4 factors are significantly associated with the risk of burnout, one negatively, compassion satisfaction, three positively, compassion fatigue, harassment experience and seniority. Conclusions: The risk of burnout is linked to subjective factors—the way quality of life at work is perceived and harassment experienced. Some professions, such as nurses, are particularly exposed and require these risk factors to be foreseen.展开更多
Background/Objective: Anemias are frequent conditions in geriatric practice. The etiologies are numerous, overlapping chronic and acute pathologies. it is also associated with high morbidity and mortality. In our cont...Background/Objective: Anemias are frequent conditions in geriatric practice. The etiologies are numerous, overlapping chronic and acute pathologies. it is also associated with high morbidity and mortality. In our context, few studies have addressed this issue, and none have been carried out in geriatric units with integrated geriatric dimensions. The aim of this study was to describe the particularities of anemia in old people in a geriatric short-stay service in Senegal. Materials and methods: This was a retrospective, descriptive study from 01 May 2019 to 31 December 2021, involving people aged 60 or over, hospitalized in the geriatrics department of Fann Hospital (Senegal) and presenting with anemia. Epidemiological, clinical and evolutionary characteristics were collected and analyzed using SPSS 24.0 software. Results: The prevalence of anemia was 32.3%. The mean age of our sample was 78.7 ± 8.5 years. Arterial high blood pressure (59.3%), diabetes mellitus (22.8%), prostate disease (12.3%) were the most frequent comorbidities. Clinical manifestations were dominated by physical asthenia (80%) and severe alteration of general condition (72%). The geriatric syndromes were essentially represented by the loss of Activities Daily Living (ADL) autonomy (65%), undernutrition (59%) and frailty (46%). The mean hemoglobin level was 8.4 g/dl ± 2.1. The main etiologies were infections (32.7%), chronic kidney disease (20.9%), iron deficiency (7.4%). The mean hospital stay was 8 days ± 3.7 days and the mortality rate was 19%. Conclusion: Anemia is a frequent occurrence in geriatric medicine, with a high morbidity and mortality rate;its expression is often atypical, with frequent geriatric syndromes;the etiologies are multiple and often interrelated, requiring an exhaustive and multidimensional approach.展开更多
Alzheimer's disease poses a significant global health challenge owing to the progressive cognitive decline of patients and absence of curative treatments.The current therapeutic strategies,primarily based on choli...Alzheimer's disease poses a significant global health challenge owing to the progressive cognitive decline of patients and absence of curative treatments.The current therapeutic strategies,primarily based on cholinesterase inhibitors and N-methyl-Daspartate receptor antagonists,offer limited symptomatic relief without halting disease progression,highlighting an urgent need for novel research directions that address the key mechanisms underlying Alzheimer's disease.Recent studies have provided insights into the critical role of glycolysis,a fundamental energy metabolism pathway in the brain,in the pathogenesis of Alzheimer's disease.Alterations in glycolytic processes within neurons and glial cells,including microglia,astrocytes,and oligodendrocytes,have been identified as significant contributors to the pathological landscape of Alzheimer's disease.Glycolytic changes impact neuronal health and function,thus offering promising targets for therapeutic intervention.The purpose of this review is to consolidate current knowledge on the modifications in glycolysis associated with Alzheimer's disease and explore the mechanisms by which these abnormalities contribute to disease onset and progression.Comprehensive focus on the pathways through which glycolytic dysfunction influences Alzheimer's disease pathology should provide insights into potential therapeutic targets and strategies that pave the way for groundbreaking treatments,emphasizing the importance of understanding metabolic processes in the quest for clarification and management of Alzheimer's disease.展开更多
Parkinson’s disease is the second most common progressive neurodegenerative disorder,and few reliable biomarkers are available to track disease progression.The proteins,DNA,mRNA,and lipids carried by exosomes reflect...Parkinson’s disease is the second most common progressive neurodegenerative disorder,and few reliable biomarkers are available to track disease progression.The proteins,DNA,mRNA,and lipids carried by exosomes reflect intracellular changes,and thus can serve as biomarkers for a variety of conditions.In this study,we investigated alterations in the protein content of plasma exosomes derived from patients with Parkinson’s disease and the potential therapeutic roles of these proteins in Parkinson’s disease.Using a tandem mass tag-based quantitative proteomics approach,we characterized the proteomes of plasma exosomes derived from individual patients,identified exosomal protein signatures specific to patients with Parkinson’s disease,and identified N-acetyl-alpha-glucosaminidase as a differentially expressed protein.N-acetyl-alpha-glucosaminidase expression levels in exosomes from the plasma of patients and healthy controls were validated by enzyme-linked immunosorbent assay and western blot.The results demonstrated that the exosomal N-acetyl-alpha-glucosaminidase concentration was not only lower in Parkinson’s disease,but also decreased with increasing Hoehn-Yahr stage,suggesting that N-acetyl-alpha-glucosaminidase could be used to rapidly evaluate Parkinson’s disease severity.Furthermore,western blot and immunohistochemistry analysis showed that N-acetyl-alpha-glucosaminidase levels were markedly reduced both in cells treated with 1-methyl-4-phenylpyridinium and cells overexpressingα-synuclein compared with control cells.Additionally,N-acetyl-alpha-glucosaminidase overexpression significantly increased cell viability and inhibitedα-synuclein expression in 1-methyl-4-phenylpyridinium-treated cells.Taken together,our findings demonstrate for the first time that exosomal N-acetyl-alpha-glucosaminidase may serve as a biomarker for Parkinson’s disease diagnosis,and that N-acetyl-alpha-glucosaminidase may reduceα-synuclein expression and 1-methyl-4-phenylpyridinium-induced neurotoxicity,thus providing a new therapeutic target for Parkinson’s disease.展开更多
With the rapidly aging human population,age-related cognitive decline and dementia are becoming increasingly prevalent worldwide.Aging is considered the main risk factor for cognitive decline and acts through alterati...With the rapidly aging human population,age-related cognitive decline and dementia are becoming increasingly prevalent worldwide.Aging is considered the main risk factor for cognitive decline and acts through alterations in the composition of the gut microbiota,microbial metabolites,and the functions of astrocytes.The microbiota–gut–brain axis has been the focus of multiple studies and is closely associated with cognitive function.This article provides a comprehensive review of the specific changes that occur in the composition of the gut microbiota and microbial metabolites in older individuals and discusses how the aging of astrocytes and reactive astrocytosis are closely related to age-related cognitive decline and neurodegenerative diseases.This article also summarizes the gut microbiota components that affect astrocyte function,mainly through the vagus nerve,immune responses,circadian rhythms,and microbial metabolites.Finally,this article summarizes the mechanism by which the gut microbiota–astrocyte axis plays a role in Alzheimer’s and Parkinson’s diseases.Our findings have revealed the critical role of the microbiota–astrocyte axis in age-related cognitive decline,aiding in a deeper understanding of potential gut microbiome-based adjuvant therapy strategies for this condition.展开更多
Brain-derived neurotrophic factor is a key factor in stress adaptation and avoidance of a social stress behavioral response.Recent studies have shown that brain-derived neurotrophic factor expression in stressed mice ...Brain-derived neurotrophic factor is a key factor in stress adaptation and avoidance of a social stress behavioral response.Recent studies have shown that brain-derived neurotrophic factor expression in stressed mice is brain region–specific,particularly involving the corticolimbic system,including the ventral tegmental area,nucleus accumbens,prefrontal cortex,amygdala,and hippocampus.Determining how brain-derived neurotrophic factor participates in stress processing in different brain regions will deepen our understanding of social stress psychopathology.In this review,we discuss the expression and regulation of brain-derived neurotrophic factor in stress-sensitive brain regions closely related to the pathophysiology of depression.We focused on associated molecular pathways and neural circuits,with special attention to the brain-derived neurotrophic factor–tropomyosin receptor kinase B signaling pathway and the ventral tegmental area–nucleus accumbens dopamine circuit.We determined that stress-induced alterations in brain-derived neurotrophic factor levels are likely related to the nature,severity,and duration of stress,especially in the above-mentioned brain regions of the corticolimbic system.Therefore,BDNF might be a biological indicator regulating stress-related processes in various brain regions.展开更多
Human brain development is a complex process,and animal models often have significant limitations.To address this,researchers have developed pluripotent stem cell-derived three-dimensional structures,known as brain-li...Human brain development is a complex process,and animal models often have significant limitations.To address this,researchers have developed pluripotent stem cell-derived three-dimensional structures,known as brain-like organoids,to more accurately model early human brain development and disease.To enable more consistent and intuitive reproduction of early brain development,in this study,we incorporated forebrain organoid culture technology into the traditional unguided method of brain organoid culture.This involved embedding organoids in matrigel for only 7 days during the rapid expansion phase of the neural epithelium and then removing them from the matrigel for further cultivation,resulting in a new type of human brain organoid system.This cerebral organoid system replicated the temporospatial characteristics of early human brain development,including neuroepithelium derivation,neural progenitor cell production and maintenance,neuron differentiation and migration,and cortical layer patterning and formation,providing more consistent and reproducible organoids for developmental modeling and toxicology testing.As a proof of concept,we applied the heavy metal cadmium to this newly improved organoid system to test whether it could be used to evaluate the neurotoxicity of environmental toxins.Brain organoids exposed to cadmium for 7 or 14 days manifested severe damage and abnormalities in their neurodevelopmental patterns,including bursts of cortical cell death and premature differentiation.Cadmium exposure caused progressive depletion of neural progenitor cells and loss of organoid integrity,accompanied by compensatory cell proliferation at ectopic locations.The convenience,flexibility,and controllability of this newly developed organoid platform make it a powerful and affordable alternative to animal models for use in neurodevelopmental,neurological,and neurotoxicological studies.展开更多
Objective The relationship between non-high-density lipoprotein(NHDL)cholesterol to high-density lipoprotein cholesterol(HDL-C)ratio(NHHR)and stoke remains unknown.This study aimed to evaluate the association between ...Objective The relationship between non-high-density lipoprotein(NHDL)cholesterol to high-density lipoprotein cholesterol(HDL-C)ratio(NHHR)and stoke remains unknown.This 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 2018.Subgroup and sensitivity analyses were conducted to test the robustness of the results.Results This study included 29,928 adult participants,of which 1,165 participants had a history of stroke.Logistic 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 analyses.Further investigation of the NHHR may enhance our understanding of stroke prevention and treatment.Conclusion Our findings suggest a positive correlation between the NHHR and an increased prevalence of stroke,potentially serving as a novel predictive factor for stroke.Timely intervention and management of the NHHR may effectively mitigate stroke occurrence.Prospective studies are required to validate this association and further explore the underlying biological mechanisms.展开更多
Objective Systematically integrate nurses’experience with“Internet Nursing Service”to analysis the nurses’experiences with“Internet Nursing Service”,and to provide a theoretical reference for formulating a more ...Objective Systematically integrate nurses’experience with“Internet Nursing Service”to analysis the nurses’experiences with“Internet Nursing Service”,and to provide a theoretical reference for formulating a more rational“Internet Nursing Service”model.Methods A systematic search in PubMed,Embase,Web of Science,the Cochrane Library,CINAHL,China National Knowledge Infrastructure(CNKI),Wanfang Database,and Chinese Biomedical Literature Database was conducted to collect qualitative research on nurses’experiences with“Internet Nursing Service,”with a retrieval time limit from December 2019 to June 2024.Qualitative meta-synthesis was performed through line-by-line coding of relevant quotes,organization of codes into descriptive themes,and development of analytical themes.Results A total of 19 studies were included,one study was rated as Grade A in quality evaluation,and the remaining studies were rated as Grade B.Collectively synthesized into three integrated results:Harvest and growth,Difficulties and challenges,and Expectations and support.Harvest and growth,include 1)manifestation of self-value,2)enhancing nursing capabilities,3)optimizing nursing resources;Difficulties and challenges,include 1)lack of safety guarantee,2)role conflict;Expectations and support include,1)expectation for professional knowledge and skill training,2)expectations for service platform optimization,3)expectation for reasonable charges,4)expectation for related policy support.Conclusion“Internet Nursing Service”model benefits both nurses and patients,but still full of challenges.It aids in the decentralization of medical resources.Management departments still need to encourage nurses to actively invest in“Internet Nursing Service”while ensuring their safety and interests.展开更多
Diabetes is highly prevalent among the elderly worldwide,with the highest number of diabetes cases in China.Yet,the management of diabetes remains unsatisfactory.Recent advances in digital health technologies have fac...Diabetes is highly prevalent among the elderly worldwide,with the highest number of diabetes cases in China.Yet,the management of diabetes remains unsatisfactory.Recent advances in digital health technologies have facilitated the establishment of smart wards for diabetes patients.There is a lack of smart wards tailored specifically for older diabetes patients who encounter unique challenges in glycemic control and diabetes management,including an increased vulnerability to hypoglycemia,the presence of multiple chronic diseases,and cognitive decline.In this review,studies on digital health technologies for diabetes in China and beyond were summarized to elucidate how the adoption of digital health technologies,such as real-time continuous glucose monitoring,sensor-augmented pump technology,and their integration with 5th generation networks,big data cloud storage,and hospital information systems,can address issues specifically related to elderly diabetes patients in hospital wards.Furthermore,the challenges and future directions for establishing and implementing smart wards for elderly diabetes patients are discussed,and these challenges may also be applicable to other countries worldwide,not just in China.Taken together,the smart wards may enhance clinical outcomes,address specific issues,and eventually improve patient-centered hospital care for elderly patients with diabetes.展开更多
The oral cavity is a complex physiological community encompassing a wide range of microorganisms.Dysbiosis of oral microbiota can lead to various oral infectious diseases,such as periodontitis and tooth decay,and even...The oral cavity is a complex physiological community encompassing a wide range of microorganisms.Dysbiosis 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 diseases.Recent studies have highlighted how oral microbes might be involved in brain aging and neurodegeneration,indicating potential avenues for intervention strategies.In 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 neurodegeneration.We also highlight advances in therapeutic development grounded in the realm of oral microbes,with the goal of advancing brain health and promoting healthy aging.展开更多
Cerebral edema caused by blood-brain barrier injury after intracerebral hemorrhage is an important factor leading to poor prognosis.Human-induced pluripotent stem cell-derived neural stem cell exosomes(hiPSC-NSC-Exos)...Cerebral edema caused by blood-brain barrier injury after intracerebral hemorrhage is an important factor leading to poor prognosis.Human-induced pluripotent stem cell-derived neural stem cell exosomes(hiPSC-NSC-Exos)have shown potential for brain injury repair in central nervous system diseases.In this study,we explored the impact of hiPSC-NSC-Exos on blood-brain barrier preservation and the underlying mechanism.Our results indicated that intranasal delivery of hiPSC-NSC-Exos mitigated neurological deficits,enhanced blood-brain barrier integrity,and reduced leukocyte infiltration in a mouse model of intracerebral hemorrhage.Additionally,hiPSC-NSC-Exos decreased immune cell infiltration,activated astrocytes,and decreased the secretion of inflammatory cytokines like monocyte chemoattractant protein-1,macrophage inflammatory protein-1α,and tumor necrosis factor-αpost-intracerebral hemorrhage,thereby improving the inflammatory microenvironment.RNA sequencing indicated that hiPSC-NSC-Exo activated the PI3K/AKT signaling pathway in astrocytes and decreased monocyte chemoattractant protein-1 secretion,thereby improving blood-brain barrier integrity.Treatment with the PI3K/AKT inhibitor LY294002 or the monocyte chemoattractant protein-1 neutralizing agent C1142 abolished these effects.In summary,our findings suggest that hiPSC-NSC-Exos maintains blood-brain barrier integrity,in part by downregulating monocyte chemoattractant protein-1 secretion through activation of the PI3K/AKT signaling pathway in astrocytes.展开更多
BACKGROUND Transforming growth factor-β(TGF-β)superfamily plays an important role in tumor progression and metastasis.Activin A receptor type 1C(ACVR1C)is a TGF-βtype I receptor that is involved in tumorigenesis th...BACKGROUND Transforming growth factor-β(TGF-β)superfamily plays an important role in tumor progression and metastasis.Activin A receptor type 1C(ACVR1C)is a TGF-βtype I receptor that is involved in tumorigenesis through binding to dif-ferent ligands.AIM To evaluate the correlation between single nucleotide polymorphisms(SNPs)of ACVR1C and susceptibility to esophageal squamous cell carcinoma(ESCC)in Chinese Han population.METHODS In this hospital-based cohort study,1043 ESCC patients and 1143 healthy controls were enrolled.Five SNPs(rs4664229,rs4556933,rs77886248,rs77263459,rs6734630)of ACVR1C were assessed by the ligation detection reaction method.Hardy-Weinberg equilibrium test,genetic model analysis,stratified analysis,linkage disequi-librium test,and haplotype analysis were conducted.RESULTS Participants carrying ACVR1C rs4556933 GA mutant had significantly decreased risk of ESCC,and those with rs77886248 TA mutant were related with higher risk,especially in older male smokers.In the haplotype analysis,ACVR1C Trs4664229Ars4556933Trs77886248Crs77263459Ars6734630 increased risk of ESCC,while Trs4664229Grs4556933Trs77886248Crs77263459Ars6734630 was associated with lower susceptibility to ESCC.CONCLUSION ACVR1C rs4556933 and rs77886248 SNPs were associated with the susceptibility to ESCC,which could provide a potential target for early diagnosis and treatment of ESCC in Chinese Han population.展开更多
BACKGROUND Early control of low-density lipoprotein cholesterol(LDL-C)is crucial for reducing the progress of cardiovascular disease.However,its additional role to the risk of primary osteoporosis in men with coronary...BACKGROUND Early control of low-density lipoprotein cholesterol(LDL-C)is crucial for reducing the progress of cardiovascular disease.However,its additional role to the risk of primary osteoporosis in men with coronary heart disease was inconclusive.Our study aims to determine the association of LDL-C and its trajectories for osteoporosis risk in the middle-aged and aged men of China.METHODS The retrospective cohort study of 1546 men aged 69.74±11.30 years conducted in Beijing,China from 2015 to 2022.And the incidence of primary osteoporosis was annually recorded.LDL-C trajectories were further identified by latent class growth model using repeated measurements of LDL-C.The association of baseline LDL-C for osteoporosis was estimated using hazard ratio(HR)with 95%CI in Cox proportional hazard model,while mean level and trajectories of LDL-C for osteoporosis were evaluated using odds ratio(OR)with 95%CI in logistic regression model.RESULTS During the median 6.2-year follow-up period,70 men developed primary osteoporosis.The higher level of baseline LDLC(HR=1.539,95%CI:1.012–2.342)and mean LDL-C(OR=2.190,95%CI:1.443–3.324)were associated with higher risk of osteoporosis in men with coronary heart disease after adjusted for covariates.Compared with those in the LDL-C trajectory of low-stable decrease,participants with medium-fluctuant trajectory,whose longitudinal LDL-C started with a medium LDL-C level and appeared an increase and then decrease,were negatively associated with osteoporosis risk(OR=2.451,95%CI:1.152–5.216).And participants with initially high LDL-C level and then a rapid decrease demonstrated a tendency towards reduced risk(OR=0.718,95%CI:0.212–2.437).CONCLUSIONS Elevated LDL-C level and its long-term fluctuation may increase the risk of primary osteoporosis in men.Early controlling a stable level of LDL-C is also essential for bone health.展开更多
High-mobility group box 1 was first discovered in the calf thymus as a DNA-binding nuclear protein and has been widely studied in diverse fields,including neurology and neuroscience.High-mobility group box 1 in the ex...High-mobility group box 1 was first discovered in the calf thymus as a DNA-binding nuclear protein and has been widely studied in diverse fields,including neurology and neuroscience.High-mobility group box 1 in the extracellular space functions as a pro-inflammatory damage-associated molecular pattern,which has been proven to play an important role in a wide variety of central nervous system disorders such as ischemic stroke,Alzheimer’s disease,frontotemporal dementia,Parkinson’s disease,multiple sclerosis,epilepsy,and traumatic brain injury.Several drugs that inhibit high-mobility group box 1 as a damage-associated molecular pattern,such as glycyrrhizin,ethyl pyruvate,and neutralizing anti-high-mobility group box 1 antibodies,are commonly used to target high-mobility group box 1 activity in central nervous system disorders.Although it is commonly known for its detrimental inflammatory effect,high-mobility group box 1 has also been shown to have beneficial pro-regenerative roles in central nervous system disorders.In this narrative review,we provide a brief summary of the history of high-mobility group box 1 research and its characterization as a damage-associated molecular pattern,its downstream receptors,and intracellular signaling pathways,how high-mobility group box 1 exerts the repair-favoring roles in general and in the central nervous system,and clues on how to differentiate the pro-regenerative from the pro-inflammatory role.Research targeting high-mobility group box 1 in the central nervous system may benefit from differentiating between the two functions rather than overall suppression of high-mobility group box 1.展开更多
Background:This study aims to identify distinct cellular subtypes within brain tissue using single-cell transcriptomic analysis,focusing on specific biomarkers that differentiate cell types and the effects of traditio...Background:This study aims to identify distinct cellular subtypes within brain tissue using single-cell transcriptomic analysis,focusing on specific biomarkers that differentiate cell types and the effects of traditional and exercise therapy.Methods:Four samples were analyzed:older control(OC),older exercise(OE),younger control(YC),and younger exercise(YE).Single-cell RNA sequencing was used to distinguish cellular subtypes through their biomarker profiles.Data visualization included violin and t-SNE plots to illustrate biomarker expression across cell clusters such as oligodendrocytes,microglia,and astrocytes.Additionally,BV2 cells were exposed to amyloid-beta fragments to simulate Alzheimer’s disease,assessing the impact of exercise-induced cellular responses.Results:Distinct cellular subtypes were identified:oligodendrocytes(MBP,St18),microglia(Dock8),and astrocytes(Aqp4,Gpc5).Sample OE was predominantly oligodendrocytes,while YE had more astrocytes,inhibitory neurons,and Canal-Retzius cells.YC showed a significant presence of Olfm3+ganglion neurons.ZEB1 gene knockout revealed changes in SMAD family gene expression,which regulate ferroptosis.Oxidative stress levels were also evaluated.Conclusion:This profiling enhances our understanding of brain cellular functions and interactions,potentially informing targeted therapies in neurological research.Exercise may influence brain cell immune responses and cell death pathways by regulating specific gene expressions,offering new insights for treating neuroinflammation and degeneration.展开更多
Objectives Diabetes remains a major global health challenge in China.Artificial intelligence(AI)has demonstrated considerable potential in improving diabetes management.This study aimed to assess healthcare providers...Objectives Diabetes remains a major global health challenge in China.Artificial intelligence(AI)has demonstrated considerable potential in improving diabetes management.This study aimed to assess healthcare providers’perceptions regarding AI in diabetes care across China.Methods A cross-sectional survey was conducted using snowball sampling from November 12 to November 24,2024.We selected 514 physicians and nurses by a snowball sampling method from healthcare providers across 30 cities or provinces in China.The self-developed questionnaire comprised five sections with 19 questions assessing medical workers’demographic characteristics,AI-related experience and interest,awareness,attitudes,and concerns regarding AI in diabetes care.Statistical analysis was performed using t-test,analysis of variance(ANOVA),and linear regression.Results Among them,20.0%and 48.1%of respondents had participated in AI-related research and training,while 85.4%expressed moderate to high interest in AI training for diabetes care.Most respondents reported partial awareness of AI in diabetes care,and only 12.6%exhibited a comprehensive or substantial understanding.Attitudes toward AI in diabetes care were generally positive,with a mean score of 24.50±3.38.Nurses demonstrated significantly higher scores than physicians(P<0.05).Greater awareness,prior AI training experience,and higher interest in AI training in diabetes care were strongly associated with more positive attitudes(P<0.05).Key concerns regarding AI included trust issues from AI-clinician inconsistencies(77.2%),increased workload and clinical workflow disruptions(63.4%),and incomplete legal and regulatory frameworks(60.3%).Only 34.2%of respondents expressed concerns about job displacement,indicating general confidence in their professional roles.Conclusions While Chinese healthcare providers show moderate awareness of AI in diabetes care,their attitudes are generally positive,and they are considerably interested in future training.Tailored,role-specific AI training is essential for equitable and effective integration into clinical practice.Additionally,transparent,reliable,ethical AI models must be prioritized to alleviate practitioners’concerns.展开更多
Short-chain fatty acids,metabolites produced by the fermentation of dietary fiber by gut microbiota,have garnered significant attention due to their correlation with neurodegenerative diseases,particularly Parkinson’...Short-chain fatty acids,metabolites produced by the fermentation of dietary fiber by gut microbiota,have garnered significant attention due to their correlation with neurodegenerative diseases,particularly Parkinson’s disease.In this review,we summarize the changes in short-chain fatty acid levels and the abundance of short-chain fatty acid-producing bacteria in various samples from patients with Parkinson’s disease,highlighting the critical role of gut homeostasis imbalance in the pathogenesis and progression of the disease.Focusing on the nervous system,we discuss the molecular mechanisms by which short-chain fatty acids influence the homeostasis of both the enteric nervous system and the central nervous system.We identify key processes,including the activation of G protein-coupled receptors and the inhibition of histone deacetylases by short-chain fatty acids.Importantly,structural or functional disruptions in the enteric nervous system mediated by these fatty acids may lead to abnormalα-synuclein expression and gastrointestinal dysmotility,which could serve as an initiating event in Parkinson’s disease.Furthermore,we propose that short-chain fatty acids help establish communication between the enteric nervous system and the central nervous system via the vagal nerve,immune circulation,and endocrine signaling.This communication may shed light on their potential role in the transmission ofα-synuclein from the gut to the brain.Finally,we elucidate novel treatment strategies for Parkinson’s disease that target short-chain fatty acids and examine the challenges associated with translating short-chain fatty acid-based therapies into clinical practice.In conclusion,this review emphasizes the pivotal role of short-chain fatty acids in regulating gut-brain axis integrity and their significance in the pathogenesis of Parkinson’s disease from the perspective of the nervous system.Moreover,it highlights the potential value of short-chain fatty acids in early intervention for Parkinson’s disease.Future research into the molecular mechanisms of short-chain fatty acids and their synergistic interactions with other gut metabolites is likely to advance the clinical translation of innovative short-chain fatty acid-based therapies for Parkinson’s disease.展开更多
BACKGROUND Type 2 diabetes mellitus(T2DM)often leads to vascular complications,such as albuminuria.The role of insulin autoantibodies(IAA)and their interaction with D-dimer in this context remains unclear.AIM To inves...BACKGROUND Type 2 diabetes mellitus(T2DM)often leads to vascular complications,such as albuminuria.The role of insulin autoantibodies(IAA)and their interaction with D-dimer in this context remains unclear.AIM To investigate the characteristics of IAA and its effect on albuminuria in T2DM patients.METHODS We retrospectively analyzed clinical data from 115 T2DM patients with positive IAA induced by exogenous insulin,and 115 age-and sex-matched IAA-negative T2DM patients as controls.Propensity scores were calculated using multivariate logistic regression.Key variables were selected using the least absolute shrinkage and selection operator(LASSO)algorithm.We constructed a prediction model and analyzed the association between IAA and albuminuria based on demographic and laboratory parameters.RESULTS The IAA-positive group had significantly higher D-dimer levels[0.30(0.19-0.55)mg/L vs 0.21(0.19-0.33)mg/L,P=0.008]and plasma insulin levels[39.1(12.0-102.7)μU/mL vs 9.8(5.5-17.6)μU/mL,P<0.001]compared to the IAA-negative group.Increases in the insulin dose per weight ratio,diabetes duration,and urinary albumin-to-creatinine ratio(UACR)were observed but did not reach statistical significance.The LASSO model identified plasma insulin and D-dimer as key factors with larger coefficients.D-dimer was significantly associated with UACR in the total and IAA-positive groups but not in the IAA-negative group.The odds ratio for D-dimer elevation(>0.5 g/L)was 2.88(95%confidence interval:1.17-7.07)in the IAA-positive group(P interaction<0.05).CONCLUSION D-dimer elevation is an independent risk factor for abnormal albuminuria and interacts with IAA in the development of abnormal albuminuria in T2DM patients.展开更多
文摘OBJECTIVES: To evaluate outcome and risk factors, particularly the (APATCHE II) score in elderly patients after admission to a geriatrics intensive care unit (ICU). Methods: A cross sectional study of patients ≥ 60 years admitted to the intensive care unit (ICU) of the Geriatrics department at Ain Shams University Hospital over 2 years period. We recorded age, sex, previous medical history, primary diagnosis, date of admission and discharge or death and APACHE II score on admission. Results: 202 patients admitted to the ICU were studied. The mean ICU mortality rates for these patients were (32, 5%), the mean APATCHE II score was (19.07). 27.3% of patients who died had hypokalemia and 43.2% had hyponatremia. Conclusion: ICU mortality rate are higher in elderly patients particularly with long ICU stay and hyponatremia.
文摘Context: Exposure to burnout of staff involved with elderly patients is dependent on many factors either personal or linked to the professional environment. Social stress and systemic problems created particularly by difficulties inherent in the French hospital management system and the way people feel it, lead to a risk of burnout. One illustration of this is the rise in suicides at work. Quality of life at work, harassment and psycho-social risks are intimately linked. Affective factors, such as suffering for the medical carers in response to the distress of their patients aggravate the risk of burnout. Methods: We have evaluated these parameters using a self-filled questionnaire form sent to all staff and filled in by computer, anonymously, in 4 establishments, in December 2012 and over the first semester of 2013. After the three factors studied by the ProQOL scale of quality of life at work, to do with burnout, satisfaction compassion and fatigue compassion, 5 other questions were added, connected with a feeling of harassment and several social and demographic matters. Burnout risk was retained on reaching a threshold of 30 for this ProQOL scale item. Results: After multivariate analysis including the parameters of the Stamm scale, harassment and the socio-demographic factors studied, (age, sex, seniority, profession, and work departments) 4 factors are significantly associated with the risk of burnout, one negatively, compassion satisfaction, three positively, compassion fatigue, harassment experience and seniority. Conclusions: The risk of burnout is linked to subjective factors—the way quality of life at work is perceived and harassment experienced. Some professions, such as nurses, are particularly exposed and require these risk factors to be foreseen.
文摘Background/Objective: Anemias are frequent conditions in geriatric practice. The etiologies are numerous, overlapping chronic and acute pathologies. it is also associated with high morbidity and mortality. In our context, few studies have addressed this issue, and none have been carried out in geriatric units with integrated geriatric dimensions. The aim of this study was to describe the particularities of anemia in old people in a geriatric short-stay service in Senegal. Materials and methods: This was a retrospective, descriptive study from 01 May 2019 to 31 December 2021, involving people aged 60 or over, hospitalized in the geriatrics department of Fann Hospital (Senegal) and presenting with anemia. Epidemiological, clinical and evolutionary characteristics were collected and analyzed using SPSS 24.0 software. Results: The prevalence of anemia was 32.3%. The mean age of our sample was 78.7 ± 8.5 years. Arterial high blood pressure (59.3%), diabetes mellitus (22.8%), prostate disease (12.3%) were the most frequent comorbidities. Clinical manifestations were dominated by physical asthenia (80%) and severe alteration of general condition (72%). The geriatric syndromes were essentially represented by the loss of Activities Daily Living (ADL) autonomy (65%), undernutrition (59%) and frailty (46%). The mean hemoglobin level was 8.4 g/dl ± 2.1. The main etiologies were infections (32.7%), chronic kidney disease (20.9%), iron deficiency (7.4%). The mean hospital stay was 8 days ± 3.7 days and the mortality rate was 19%. Conclusion: Anemia is a frequent occurrence in geriatric medicine, with a high morbidity and mortality rate;its expression is often atypical, with frequent geriatric syndromes;the etiologies are multiple and often interrelated, requiring an exhaustive and multidimensional approach.
基金supported by the National Natural Science Foundation of China,No.82271214(to ZY)the Natural Science Foundation of Hubei Province of China,No.2022CFB109(to ZY)。
文摘Alzheimer's disease poses a significant global health challenge owing to the progressive cognitive decline of patients and absence of curative treatments.The current therapeutic strategies,primarily based on cholinesterase inhibitors and N-methyl-Daspartate receptor antagonists,offer limited symptomatic relief without halting disease progression,highlighting an urgent need for novel research directions that address the key mechanisms underlying Alzheimer's disease.Recent studies have provided insights into the critical role of glycolysis,a fundamental energy metabolism pathway in the brain,in the pathogenesis of Alzheimer's disease.Alterations in glycolytic processes within neurons and glial cells,including microglia,astrocytes,and oligodendrocytes,have been identified as significant contributors to the pathological landscape of Alzheimer's disease.Glycolytic changes impact neuronal health and function,thus offering promising targets for therapeutic intervention.The purpose of this review is to consolidate current knowledge on the modifications in glycolysis associated with Alzheimer's disease and explore the mechanisms by which these abnormalities contribute to disease onset and progression.Comprehensive focus on the pathways through which glycolytic dysfunction influences Alzheimer's disease pathology should provide insights into potential therapeutic targets and strategies that pave the way for groundbreaking treatments,emphasizing the importance of understanding metabolic processes in the quest for clarification and management of Alzheimer's disease.
基金supported by the Science and Technology(S&T)Program of Hebei Province,No.22377798D(to YZ).
文摘Parkinson’s disease is the second most common progressive neurodegenerative disorder,and few reliable biomarkers are available to track disease progression.The proteins,DNA,mRNA,and lipids carried by exosomes reflect intracellular changes,and thus can serve as biomarkers for a variety of conditions.In this study,we investigated alterations in the protein content of plasma exosomes derived from patients with Parkinson’s disease and the potential therapeutic roles of these proteins in Parkinson’s disease.Using a tandem mass tag-based quantitative proteomics approach,we characterized the proteomes of plasma exosomes derived from individual patients,identified exosomal protein signatures specific to patients with Parkinson’s disease,and identified N-acetyl-alpha-glucosaminidase as a differentially expressed protein.N-acetyl-alpha-glucosaminidase expression levels in exosomes from the plasma of patients and healthy controls were validated by enzyme-linked immunosorbent assay and western blot.The results demonstrated that the exosomal N-acetyl-alpha-glucosaminidase concentration was not only lower in Parkinson’s disease,but also decreased with increasing Hoehn-Yahr stage,suggesting that N-acetyl-alpha-glucosaminidase could be used to rapidly evaluate Parkinson’s disease severity.Furthermore,western blot and immunohistochemistry analysis showed that N-acetyl-alpha-glucosaminidase levels were markedly reduced both in cells treated with 1-methyl-4-phenylpyridinium and cells overexpressingα-synuclein compared with control cells.Additionally,N-acetyl-alpha-glucosaminidase overexpression significantly increased cell viability and inhibitedα-synuclein expression in 1-methyl-4-phenylpyridinium-treated cells.Taken together,our findings demonstrate for the first time that exosomal N-acetyl-alpha-glucosaminidase may serve as a biomarker for Parkinson’s disease diagnosis,and that N-acetyl-alpha-glucosaminidase may reduceα-synuclein expression and 1-methyl-4-phenylpyridinium-induced neurotoxicity,thus providing a new therapeutic target for Parkinson’s disease.
基金supported by the Haihe Laboratory of Cell Ecosystem Innovation Foundation,No.22HHXBSS00047(to PL)Graduate Science and Technology Innovation Project of Tianjin,No.2022BKY173(to LZ)Tianjin Municipal Science and Technology Bureau Foundation,No.20201194(to PL).
文摘With the rapidly aging human population,age-related cognitive decline and dementia are becoming increasingly prevalent worldwide.Aging is considered the main risk factor for cognitive decline and acts through alterations in the composition of the gut microbiota,microbial metabolites,and the functions of astrocytes.The microbiota–gut–brain axis has been the focus of multiple studies and is closely associated with cognitive function.This article provides a comprehensive review of the specific changes that occur in the composition of the gut microbiota and microbial metabolites in older individuals and discusses how the aging of astrocytes and reactive astrocytosis are closely related to age-related cognitive decline and neurodegenerative diseases.This article also summarizes the gut microbiota components that affect astrocyte function,mainly through the vagus nerve,immune responses,circadian rhythms,and microbial metabolites.Finally,this article summarizes the mechanism by which the gut microbiota–astrocyte axis plays a role in Alzheimer’s and Parkinson’s diseases.Our findings have revealed the critical role of the microbiota–astrocyte axis in age-related cognitive decline,aiding in a deeper understanding of potential gut microbiome-based adjuvant therapy strategies for this condition.
基金supported financially by the National Natural Science Foundation of China,No.82071272(to YZ).
文摘Brain-derived neurotrophic factor is a key factor in stress adaptation and avoidance of a social stress behavioral response.Recent studies have shown that brain-derived neurotrophic factor expression in stressed mice is brain region–specific,particularly involving the corticolimbic system,including the ventral tegmental area,nucleus accumbens,prefrontal cortex,amygdala,and hippocampus.Determining how brain-derived neurotrophic factor participates in stress processing in different brain regions will deepen our understanding of social stress psychopathology.In this review,we discuss the expression and regulation of brain-derived neurotrophic factor in stress-sensitive brain regions closely related to the pathophysiology of depression.We focused on associated molecular pathways and neural circuits,with special attention to the brain-derived neurotrophic factor–tropomyosin receptor kinase B signaling pathway and the ventral tegmental area–nucleus accumbens dopamine circuit.We determined that stress-induced alterations in brain-derived neurotrophic factor levels are likely related to the nature,severity,and duration of stress,especially in the above-mentioned brain regions of the corticolimbic system.Therefore,BDNF might be a biological indicator regulating stress-related processes in various brain regions.
基金supported by the National Key R&D Program of China,No.2019YFA0110300(to ZG)the National Natural Science Foundation of China,Nos.81773302(to YF),32070862(to ZG).
文摘Human brain development is a complex process,and animal models often have significant limitations.To address this,researchers have developed pluripotent stem cell-derived three-dimensional structures,known as brain-like organoids,to more accurately model early human brain development and disease.To enable more consistent and intuitive reproduction of early brain development,in this study,we incorporated forebrain organoid culture technology into the traditional unguided method of brain organoid culture.This involved embedding organoids in matrigel for only 7 days during the rapid expansion phase of the neural epithelium and then removing them from the matrigel for further cultivation,resulting in a new type of human brain organoid system.This cerebral organoid system replicated the temporospatial characteristics of early human brain development,including neuroepithelium derivation,neural progenitor cell production and maintenance,neuron differentiation and migration,and cortical layer patterning and formation,providing more consistent and reproducible organoids for developmental modeling and toxicology testing.As a proof of concept,we applied the heavy metal cadmium to this newly improved organoid system to test whether it could be used to evaluate the neurotoxicity of environmental toxins.Brain organoids exposed to cadmium for 7 or 14 days manifested severe damage and abnormalities in their neurodevelopmental patterns,including bursts of cortical cell death and premature differentiation.Cadmium exposure caused progressive depletion of neural progenitor cells and loss of organoid integrity,accompanied by compensatory cell proliferation at ectopic locations.The convenience,flexibility,and controllability of this newly developed organoid platform make it a powerful and affordable alternative to animal models for use in neurodevelopmental,neurological,and neurotoxicological studies.
文摘Objective The relationship between non-high-density lipoprotein(NHDL)cholesterol to high-density lipoprotein cholesterol(HDL-C)ratio(NHHR)and stoke remains unknown.This 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 2018.Subgroup and sensitivity analyses were conducted to test the robustness of the results.Results This study included 29,928 adult participants,of which 1,165 participants had a history of stroke.Logistic 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 analyses.Further investigation of the NHHR may enhance our understanding of stroke prevention and treatment.Conclusion Our findings suggest a positive correlation between the NHHR and an increased prevalence of stroke,potentially serving as a novel predictive factor for stroke.Timely intervention and management of the NHHR may effectively mitigate stroke occurrence.Prospective studies are required to validate this association and further explore the underlying biological mechanisms.
基金supported by the General Project of the Cultivation Project of the Chinese Hospital Reform and Development Research Institute of Nanjing University(NDYG2022072)。
文摘Objective Systematically integrate nurses’experience with“Internet Nursing Service”to analysis the nurses’experiences with“Internet Nursing Service”,and to provide a theoretical reference for formulating a more rational“Internet Nursing Service”model.Methods A systematic search in PubMed,Embase,Web of Science,the Cochrane Library,CINAHL,China National Knowledge Infrastructure(CNKI),Wanfang Database,and Chinese Biomedical Literature Database was conducted to collect qualitative research on nurses’experiences with“Internet Nursing Service,”with a retrieval time limit from December 2019 to June 2024.Qualitative meta-synthesis was performed through line-by-line coding of relevant quotes,organization of codes into descriptive themes,and development of analytical themes.Results A total of 19 studies were included,one study was rated as Grade A in quality evaluation,and the remaining studies were rated as Grade B.Collectively synthesized into three integrated results:Harvest and growth,Difficulties and challenges,and Expectations and support.Harvest and growth,include 1)manifestation of self-value,2)enhancing nursing capabilities,3)optimizing nursing resources;Difficulties and challenges,include 1)lack of safety guarantee,2)role conflict;Expectations and support include,1)expectation for professional knowledge and skill training,2)expectations for service platform optimization,3)expectation for reasonable charges,4)expectation for related policy support.Conclusion“Internet Nursing Service”model benefits both nurses and patients,but still full of challenges.It aids in the decentralization of medical resources.Management departments still need to encourage nurses to actively invest in“Internet Nursing Service”while ensuring their safety and interests.
基金Supported by Post-Subsidy Funds from the National Clinical Research Center,Ministry of Science and Technology of China,No.303-01-001-0272-08Beijing Municipal Administration of Hospitals Incubating Program,No.PX2022032Beijing Municipal Public Welfare Development and Reform Pilot Project for Medical Research Institutes(PWD&RPP-MRI),No.JYY2023-13.
文摘Diabetes is highly prevalent among the elderly worldwide,with the highest number of diabetes cases in China.Yet,the management of diabetes remains unsatisfactory.Recent advances in digital health technologies have facilitated the establishment of smart wards for diabetes patients.There is a lack of smart wards tailored specifically for older diabetes patients who encounter unique challenges in glycemic control and diabetes management,including an increased vulnerability to hypoglycemia,the presence of multiple chronic diseases,and cognitive decline.In this review,studies on digital health technologies for diabetes in China and beyond were summarized to elucidate how the adoption of digital health technologies,such as real-time continuous glucose monitoring,sensor-augmented pump technology,and their integration with 5th generation networks,big data cloud storage,and hospital information systems,can address issues specifically related to elderly diabetes patients in hospital wards.Furthermore,the challenges and future directions for establishing and implementing smart wards for elderly diabetes patients are discussed,and these challenges may also be applicable to other countries worldwide,not just in China.Taken together,the smart wards may enhance clinical outcomes,address specific issues,and eventually improve patient-centered hospital care for elderly patients with diabetes.
基金supported by the National Natural Science Foundation of China,No.81921006(to GHL)。
文摘The oral cavity is a complex physiological community encompassing a wide range of microorganisms.Dysbiosis 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 diseases.Recent studies have highlighted how oral microbes might be involved in brain aging and neurodegeneration,indicating potential avenues for intervention strategies.In 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 neurodegeneration.We also highlight advances in therapeutic development grounded in the realm of oral microbes,with the goal of advancing brain health and promoting healthy aging.
基金supported by the National Natural Science Foundation of China,No.8227050826(to PL)Tianjin Science and Technology Bureau Foundation,No.20201194(to PL)Tianjin Graduate Research and Innovation Project,No.2022BKY174(to CW).
文摘Cerebral edema caused by blood-brain barrier injury after intracerebral hemorrhage is an important factor leading to poor prognosis.Human-induced pluripotent stem cell-derived neural stem cell exosomes(hiPSC-NSC-Exos)have shown potential for brain injury repair in central nervous system diseases.In this study,we explored the impact of hiPSC-NSC-Exos on blood-brain barrier preservation and the underlying mechanism.Our results indicated that intranasal delivery of hiPSC-NSC-Exos mitigated neurological deficits,enhanced blood-brain barrier integrity,and reduced leukocyte infiltration in a mouse model of intracerebral hemorrhage.Additionally,hiPSC-NSC-Exos decreased immune cell infiltration,activated astrocytes,and decreased the secretion of inflammatory cytokines like monocyte chemoattractant protein-1,macrophage inflammatory protein-1α,and tumor necrosis factor-αpost-intracerebral hemorrhage,thereby improving the inflammatory microenvironment.RNA sequencing indicated that hiPSC-NSC-Exo activated the PI3K/AKT signaling pathway in astrocytes and decreased monocyte chemoattractant protein-1 secretion,thereby improving blood-brain barrier integrity.Treatment with the PI3K/AKT inhibitor LY294002 or the monocyte chemoattractant protein-1 neutralizing agent C1142 abolished these effects.In summary,our findings suggest that hiPSC-NSC-Exos maintains blood-brain barrier integrity,in part by downregulating monocyte chemoattractant protein-1 secretion through activation of the PI3K/AKT signaling pathway in astrocytes.
基金Supported by The National Natural Science Foundation of China,No.82350127 and No.82241013the Shanghai Natural Science Foundation,No.20ZR1411600+2 种基金the Shanghai Shenkang Hospital Development Center,No.SHDC2020CR4039the Bethune Ethicon Excellent Surgery Foundation,No.CESS2021TC04Xuhui District Medical Research Project of Shanghai,No.SHXH201805.
文摘BACKGROUND Transforming growth factor-β(TGF-β)superfamily plays an important role in tumor progression and metastasis.Activin A receptor type 1C(ACVR1C)is a TGF-βtype I receptor that is involved in tumorigenesis through binding to dif-ferent ligands.AIM To evaluate the correlation between single nucleotide polymorphisms(SNPs)of ACVR1C and susceptibility to esophageal squamous cell carcinoma(ESCC)in Chinese Han population.METHODS In this hospital-based cohort study,1043 ESCC patients and 1143 healthy controls were enrolled.Five SNPs(rs4664229,rs4556933,rs77886248,rs77263459,rs6734630)of ACVR1C were assessed by the ligation detection reaction method.Hardy-Weinberg equilibrium test,genetic model analysis,stratified analysis,linkage disequi-librium test,and haplotype analysis were conducted.RESULTS Participants carrying ACVR1C rs4556933 GA mutant had significantly decreased risk of ESCC,and those with rs77886248 TA mutant were related with higher risk,especially in older male smokers.In the haplotype analysis,ACVR1C Trs4664229Ars4556933Trs77886248Crs77263459Ars6734630 increased risk of ESCC,while Trs4664229Grs4556933Trs77886248Crs77263459Ars6734630 was associated with lower susceptibility to ESCC.CONCLUSION ACVR1C rs4556933 and rs77886248 SNPs were associated with the susceptibility to ESCC,which could provide a potential target for early diagnosis and treatment of ESCC in Chinese Han population.
基金supported by the Multi-center RCT Clinical Project of the National Clinical Research Center for Geriatric Diseases,Chinese PLA General Hospital(NCRCGPLAGH-2023001)the Beijing Nova Program(No.20220484020)+1 种基金the Beijing Natural Science Foundation(No.7252181)the Capital’s Funds for Health Improvement and Research(No.2024-2G-5033).
文摘BACKGROUND Early control of low-density lipoprotein cholesterol(LDL-C)is crucial for reducing the progress of cardiovascular disease.However,its additional role to the risk of primary osteoporosis in men with coronary heart disease was inconclusive.Our study aims to determine the association of LDL-C and its trajectories for osteoporosis risk in the middle-aged and aged men of China.METHODS The retrospective cohort study of 1546 men aged 69.74±11.30 years conducted in Beijing,China from 2015 to 2022.And the incidence of primary osteoporosis was annually recorded.LDL-C trajectories were further identified by latent class growth model using repeated measurements of LDL-C.The association of baseline LDL-C for osteoporosis was estimated using hazard ratio(HR)with 95%CI in Cox proportional hazard model,while mean level and trajectories of LDL-C for osteoporosis were evaluated using odds ratio(OR)with 95%CI in logistic regression model.RESULTS During the median 6.2-year follow-up period,70 men developed primary osteoporosis.The higher level of baseline LDLC(HR=1.539,95%CI:1.012–2.342)and mean LDL-C(OR=2.190,95%CI:1.443–3.324)were associated with higher risk of osteoporosis in men with coronary heart disease after adjusted for covariates.Compared with those in the LDL-C trajectory of low-stable decrease,participants with medium-fluctuant trajectory,whose longitudinal LDL-C started with a medium LDL-C level and appeared an increase and then decrease,were negatively associated with osteoporosis risk(OR=2.451,95%CI:1.152–5.216).And participants with initially high LDL-C level and then a rapid decrease demonstrated a tendency towards reduced risk(OR=0.718,95%CI:0.212–2.437).CONCLUSIONS Elevated LDL-C level and its long-term fluctuation may increase the risk of primary osteoporosis in men.Early controlling a stable level of LDL-C is also essential for bone health.
基金supported by a grant of the M.D.-Ph.D./Medical Scientist Training Program through the Korea Health Industry Development Institute(KHIDI)funded by the Ministry of Health&Welfare,Republic of Korea(to HK)+3 种基金supported by National Research Foundation of Korea(NRF)grants funded by the Korean government(MSITMinistry of Science and ICT)(NRF2019R1A5A2026045 and NRF-2021R1F1A1061819)a grant from the Korean Health Technology R&D Project through the Korea Health Industry Development Institute(KHIDI),funded by the Ministry of Health&Welfare,Republic of Korea(HR21C1003)New Faculty Research Fund of Ajou University School of Medicine(to JYC)。
文摘High-mobility group box 1 was first discovered in the calf thymus as a DNA-binding nuclear protein and has been widely studied in diverse fields,including neurology and neuroscience.High-mobility group box 1 in the extracellular space functions as a pro-inflammatory damage-associated molecular pattern,which has been proven to play an important role in a wide variety of central nervous system disorders such as ischemic stroke,Alzheimer’s disease,frontotemporal dementia,Parkinson’s disease,multiple sclerosis,epilepsy,and traumatic brain injury.Several drugs that inhibit high-mobility group box 1 as a damage-associated molecular pattern,such as glycyrrhizin,ethyl pyruvate,and neutralizing anti-high-mobility group box 1 antibodies,are commonly used to target high-mobility group box 1 activity in central nervous system disorders.Although it is commonly known for its detrimental inflammatory effect,high-mobility group box 1 has also been shown to have beneficial pro-regenerative roles in central nervous system disorders.In this narrative review,we provide a brief summary of the history of high-mobility group box 1 research and its characterization as a damage-associated molecular pattern,its downstream receptors,and intracellular signaling pathways,how high-mobility group box 1 exerts the repair-favoring roles in general and in the central nervous system,and clues on how to differentiate the pro-regenerative from the pro-inflammatory role.Research targeting high-mobility group box 1 in the central nervous system may benefit from differentiating between the two functions rather than overall suppression of high-mobility group box 1.
文摘Background:This study aims to identify distinct cellular subtypes within brain tissue using single-cell transcriptomic analysis,focusing on specific biomarkers that differentiate cell types and the effects of traditional and exercise therapy.Methods:Four samples were analyzed:older control(OC),older exercise(OE),younger control(YC),and younger exercise(YE).Single-cell RNA sequencing was used to distinguish cellular subtypes through their biomarker profiles.Data visualization included violin and t-SNE plots to illustrate biomarker expression across cell clusters such as oligodendrocytes,microglia,and astrocytes.Additionally,BV2 cells were exposed to amyloid-beta fragments to simulate Alzheimer’s disease,assessing the impact of exercise-induced cellular responses.Results:Distinct cellular subtypes were identified:oligodendrocytes(MBP,St18),microglia(Dock8),and astrocytes(Aqp4,Gpc5).Sample OE was predominantly oligodendrocytes,while YE had more astrocytes,inhibitory neurons,and Canal-Retzius cells.YC showed a significant presence of Olfm3+ganglion neurons.ZEB1 gene knockout revealed changes in SMAD family gene expression,which regulate ferroptosis.Oxidative stress levels were also evaluated.Conclusion:This profiling enhances our understanding of brain cellular functions and interactions,potentially informing targeted therapies in neurological research.Exercise may influence brain cell immune responses and cell death pathways by regulating specific gene expressions,offering new insights for treating neuroinflammation and degeneration.
基金supported by the Jiangsu Provincial Department of Science and Technology Social Development Project(No.BE2020787)。
文摘Objectives Diabetes remains a major global health challenge in China.Artificial intelligence(AI)has demonstrated considerable potential in improving diabetes management.This study aimed to assess healthcare providers’perceptions regarding AI in diabetes care across China.Methods A cross-sectional survey was conducted using snowball sampling from November 12 to November 24,2024.We selected 514 physicians and nurses by a snowball sampling method from healthcare providers across 30 cities or provinces in China.The self-developed questionnaire comprised five sections with 19 questions assessing medical workers’demographic characteristics,AI-related experience and interest,awareness,attitudes,and concerns regarding AI in diabetes care.Statistical analysis was performed using t-test,analysis of variance(ANOVA),and linear regression.Results Among them,20.0%and 48.1%of respondents had participated in AI-related research and training,while 85.4%expressed moderate to high interest in AI training for diabetes care.Most respondents reported partial awareness of AI in diabetes care,and only 12.6%exhibited a comprehensive or substantial understanding.Attitudes toward AI in diabetes care were generally positive,with a mean score of 24.50±3.38.Nurses demonstrated significantly higher scores than physicians(P<0.05).Greater awareness,prior AI training experience,and higher interest in AI training in diabetes care were strongly associated with more positive attitudes(P<0.05).Key concerns regarding AI included trust issues from AI-clinician inconsistencies(77.2%),increased workload and clinical workflow disruptions(63.4%),and incomplete legal and regulatory frameworks(60.3%).Only 34.2%of respondents expressed concerns about job displacement,indicating general confidence in their professional roles.Conclusions While Chinese healthcare providers show moderate awareness of AI in diabetes care,their attitudes are generally positive,and they are considerably interested in future training.Tailored,role-specific AI training is essential for equitable and effective integration into clinical practice.Additionally,transparent,reliable,ethical AI models must be prioritized to alleviate practitioners’concerns.
基金supported by the National Key R&D Program of China,No.2021YFC2501200(to PC).
文摘Short-chain fatty acids,metabolites produced by the fermentation of dietary fiber by gut microbiota,have garnered significant attention due to their correlation with neurodegenerative diseases,particularly Parkinson’s disease.In this review,we summarize the changes in short-chain fatty acid levels and the abundance of short-chain fatty acid-producing bacteria in various samples from patients with Parkinson’s disease,highlighting the critical role of gut homeostasis imbalance in the pathogenesis and progression of the disease.Focusing on the nervous system,we discuss the molecular mechanisms by which short-chain fatty acids influence the homeostasis of both the enteric nervous system and the central nervous system.We identify key processes,including the activation of G protein-coupled receptors and the inhibition of histone deacetylases by short-chain fatty acids.Importantly,structural or functional disruptions in the enteric nervous system mediated by these fatty acids may lead to abnormalα-synuclein expression and gastrointestinal dysmotility,which could serve as an initiating event in Parkinson’s disease.Furthermore,we propose that short-chain fatty acids help establish communication between the enteric nervous system and the central nervous system via the vagal nerve,immune circulation,and endocrine signaling.This communication may shed light on their potential role in the transmission ofα-synuclein from the gut to the brain.Finally,we elucidate novel treatment strategies for Parkinson’s disease that target short-chain fatty acids and examine the challenges associated with translating short-chain fatty acid-based therapies into clinical practice.In conclusion,this review emphasizes the pivotal role of short-chain fatty acids in regulating gut-brain axis integrity and their significance in the pathogenesis of Parkinson’s disease from the perspective of the nervous system.Moreover,it highlights the potential value of short-chain fatty acids in early intervention for Parkinson’s disease.Future research into the molecular mechanisms of short-chain fatty acids and their synergistic interactions with other gut metabolites is likely to advance the clinical translation of innovative short-chain fatty acid-based therapies for Parkinson’s disease.
文摘BACKGROUND Type 2 diabetes mellitus(T2DM)often leads to vascular complications,such as albuminuria.The role of insulin autoantibodies(IAA)and their interaction with D-dimer in this context remains unclear.AIM To investigate the characteristics of IAA and its effect on albuminuria in T2DM patients.METHODS We retrospectively analyzed clinical data from 115 T2DM patients with positive IAA induced by exogenous insulin,and 115 age-and sex-matched IAA-negative T2DM patients as controls.Propensity scores were calculated using multivariate logistic regression.Key variables were selected using the least absolute shrinkage and selection operator(LASSO)algorithm.We constructed a prediction model and analyzed the association between IAA and albuminuria based on demographic and laboratory parameters.RESULTS The IAA-positive group had significantly higher D-dimer levels[0.30(0.19-0.55)mg/L vs 0.21(0.19-0.33)mg/L,P=0.008]and plasma insulin levels[39.1(12.0-102.7)μU/mL vs 9.8(5.5-17.6)μU/mL,P<0.001]compared to the IAA-negative group.Increases in the insulin dose per weight ratio,diabetes duration,and urinary albumin-to-creatinine ratio(UACR)were observed but did not reach statistical significance.The LASSO model identified plasma insulin and D-dimer as key factors with larger coefficients.D-dimer was significantly associated with UACR in the total and IAA-positive groups but not in the IAA-negative group.The odds ratio for D-dimer elevation(>0.5 g/L)was 2.88(95%confidence interval:1.17-7.07)in the IAA-positive group(P interaction<0.05).CONCLUSION D-dimer elevation is an independent risk factor for abnormal albuminuria and interacts with IAA in the development of abnormal albuminuria in T2DM patients.
