As a critical department ensuring the sterility of hospital instruments,the Sterile Supply Center(SSC)directly impacts the sterility status of clinical instruments through its sterilization qualification rate.Geriatri...As a critical department ensuring the sterility of hospital instruments,the Sterile Supply Center(SSC)directly impacts the sterility status of clinical instruments through its sterilization qualification rate.Geriatric patients,due to physiological decline and compromised immune function,constitute a high-risk group for hospital-acquired infections,with more stringent requirements for instrument sterility.This paper analyzes the current status and influencing factors of sterilization qualification rates in SSCs,explores the mechanistic association between sterilization qualification rates and infections in geriatric departments,and proposes targeted strategies to improve sterilization qualification rates.It highlights the pivotal role of SSC instrument sterilization in infection prevention and control for geriatric patients,providing theoretical basis and practical guidance for optimizing SSC management,reducing infection rates in geriatric departments,and ensuring the safety of elderly patients’medical care.These findings aim to enhance overall infection management standards in hospitals.展开更多
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
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
Brain insulin resistance(BIR)is a prevalent detrimental feature of Alzheimer’s disease(AD)and all-cause dementia.Therapies designed to activate insulin signaling and enhance insulin receptor sensitivity have proven b...Brain insulin resistance(BIR)is a prevalent detrimental feature of Alzheimer’s disease(AD)and all-cause dementia.Therapies designed to activate insulin signaling and enhance insulin receptor sensitivity have proven beneficial for cognitive enhancement in pre-clinical models,non-human primates,and humans.BIR encompasses dysregulated brain insulin signaling,which is either due to insulin receptor resistance,reduced insulin receptor levels,or reduced levels of insulin in the brain,affecting processes involved in AD development and progression.展开更多
Background:The aim of the study was to develop a non-human primate model of metabolic dysfunction in Macaca fascicularis using chronic high-fat diet(HFD)to mimic clinical disease progression.Methods:Thirty-five male m...Background:The aim of the study was to develop a non-human primate model of metabolic dysfunction in Macaca fascicularis using chronic high-fat diet(HFD)to mimic clinical disease progression.Methods:Thirty-five male macaques aged 10-15 years underwent an 18-month HFD intervention.Physiological parameters(BMI,BP,hematology),liver fat fraction(evaluated by ultrasound/MRI),cardiac function(assessed by echocardiography),and histopathology(using liver biopsy)were measured before and after the intervention.Serum proteomics with KEGG/STRING analyses identified molecular mechanisms.Results:Within 6 months,HFD induced dyslipidemia(elevated TG,TCHO,HDL-C,LDL-C).After 18 months,metabolic dysfunction-associated steatohepatitis(MASH)was confirmed by histopathology in 57.14%(16/28)of macaques,diabetes(elevated FPG/HbA1c)in 17.86%(5/28),and myocardial hypertrophy(elevated LVMass/LAD)in 46.43%(13/28).Proteomics identified Bile acid-CoA:amino acid N-acyltransferase(BAAT)as a MASH hallmark protein,the level of which was inversely correlated with the degree of fibrosis.For diabetes,citrate synthase(CS)and malate dehydrogenase 1(MDH1)impaired glucose oxidation via the TCA cycle,while hexose-6-phosphate de-hydrogenase(H6PD)disrupted gluconeogenesis.Myocardial hypertrophy was associ-ated with the downregulation of SRC proto-oncogene,non-receptor tyrosine kinase(SRC),mitogen-activated protein kinase 14(MAPK14),emerin(EMD),and integrin subunit beta 1(ITGB1).Conclusions:An 18-month HFD successfully established a translational M.fascicula-ris model replicating key metabolic disorders(MASH,diabetes,cardiac hypertrophy).BAAT,CS/MDH1/H6PD,and SRC/MAPK14/EMD/ITGB1 were identified as mecha-nistic biomarkers for these conditions.展开更多
Mitophagy is a well-characterized and redundant recycling system for damaged mitochondria and a marker of organelle quality(Picca et al.,2023).Yet,the assessment of mitophagy in vivo remains a challenge.The characteri...Mitophagy is a well-characterized and redundant recycling system for damaged mitochondria and a marker of organelle quality(Picca et al.,2023).Yet,the assessment of mitophagy in vivo remains a challenge.The characterization of the endosomallysosomal pathways supporting the endocytic tra fficking has provided invaluable information also into mitophagy signaling.展开更多
Sarcopenia in the elderly is a syndrome characterized by age-related progressive loss of muscle mass, decline in muscle strength, and deterioration of muscle function. Its high incidence significantly increases the ri...Sarcopenia in the elderly is a syndrome characterized by age-related progressive loss of muscle mass, decline in muscle strength, and deterioration of muscle function. Its high incidence significantly increases the risk of falls, fractures, disability, and mortality among the elderly, posing a global public health challenge for geriatric health. Insulin-like growth factor-1 (IGF-1), a key cytokine regulating muscle growth, repair, and metabolism, exhibits a progressive decline in serum levels with aging and is closely associated with the onset and progression of sarcopenia in the elderly. This study reviews the research progress of IGF-1 in the diagnosis and efficacy prediction of sarcopenia in the elderly, providing theoretical references for precise diagnosis, treatment, and prognosis assessment of sarcopenia in the elderly.展开更多
Background:Repetitive mild traumatic brain injury(rmTBI)is a significant risk factor for neurodegeneration,characterized by pathological protein deposition and persistent neuroinflammation.Research has observed increa...Background:Repetitive mild traumatic brain injury(rmTBI)is a significant risk factor for neurodegeneration,characterized by pathological protein deposition and persistent neuroinflammation.Research has observed increased interleukin-33(IL-33)levels in the peripheral blood of patients with rmTBI,suggesting IL-33 may participate in regulating the pathological development of rmTBI.The study aims to elucidate the impact and mechanism of IL-33 in the progression of neuropathology following rmTBI,and to explore its potential as a therapeutic target to improve the neurological outcome.Methods:The study employed an rmTBI mouse model using the wild-type(WT)and IL-33 knockout mice.Cognitive function was assessed via the Y-maze and Barnes tests.The main cell type expressing IL-33 and its receptor,suppression of tumorigenicity 2(ST2),was then investigated in the mouse brain through immunofluorescence colocalization.As the primary neural cell responsible for ST2 expression,microglia were studied in vitro using the BV2 cell line.The effects of lipid droplets(LDs)accumulation and amyloid-beta(Aβ)phagocytosis were measured to elucidate the impact of IL-33 on BV2 cells'phagocytosis.Additionally,HT22 neuronal apoptosis was assessed by flow cytometry.Finally,the cognitive effects of intranasal administration of IL-33 were evaluated in mice.Results:IL-33 KO mice exhibited pronounced cognitive impairment after rmTBI.In the mouse brain,astrocytes were identified as the primary source of IL-33 secretion,while microglia predominantly expressed ST2.Transcriptome sequencing revealed that IL-33 significantly influenced phagocytosis function.IL-33 mitigated LDs accumulation in BV2 cells and enhanced Aβphagocytosis in vitro.In addition,the culture medium of BV2 cells with activated IL-33/ST2 signaling reduced HT22 neuronal apoptosis and axonal damage.Furthermore,intranasal administration of IL-33 was observed to be effective in alleviating neurodegeneration and cognitive outcome of rmTBI mice.Conclusions:Dysfunction of the IL-33/ST2 axis following rmTBI leads to cognitive dysfunction via impairing microglial phagocytosis capacity and promoting neuronal damage.IL-33 would be a promising therapeutic target for alleviating neurodegeneration following rmTBI.展开更多
Parkinson’s disease is the second most common neurodegenerative disorder.ATPase H+transporting V0 subunit A1(ATP6V0A1)is a component of vacuolar H+-ATPase(V-ATPase),an ATP-dependent proton pump.Our previous research ...Parkinson’s disease is the second most common neurodegenerative disorder.ATPase H+transporting V0 subunit A1(ATP6V0A1)is a component of vacuolar H+-ATPase(V-ATPase),an ATP-dependent proton pump.Our previous research identified an association between the ATP6V0A1 rs601999 variant and Parkinson’s disease;however,the underlying mechanisms of ATP6V0A1 in Parkinson’s disease remain elusive.In this study,we generated ATP6V0A1 knockdown and overexpression models and then examined the degeneration of dopaminergic neurons,lysosomal function,and the autophagy-lysosomal pathway using immunohistochemistry,western blotting,and transmission electron microscopy.We found that ATP6V0A1 protected against lysosomal dysfunction,regulated autophagic flux,and decreased phosphorylatedα-synuclein levels in vitro.In vivo,ATP6V0A1 reduced levels ofα-synuclein and phosphorylatedα-synuclein proteins,mitigated degeneration of dopaminergic neurons,and improved motor dysfunction.Collectively,these findings show that ATP6V0A1 plays a protective role in Parkinson’s disease by modulating the autophagy-lysosomal pathway.A correlation between ATP6V0A1 and Parkinson’s disease susceptibility may serve as a biomarker for Parkinson’s disease,while the protective effects of ATP6V0A1 could represent a potential therapeutic target for the disease.展开更多
Objective Frailty is becoming increasingly common among aging adults.Frailty transitionis shaped by biological,social,psychological,and environmental factors.This study investigated combined effects of protective fact...Objective Frailty is becoming increasingly common among aging adults.Frailty transitionis shaped by biological,social,psychological,and environmental factors.This study investigated combined effects of protective factors on frailty transition by constructing a Protection Index(PI)to guide targeted interventions.Methods Data were extracted from the 4th Sample Survey of the Aged Population in Urban and Rural China,including baseline(2017)and follow-up(2019)surveys.Frailty was assessed using the Frailty Index(FI),whereas the PI measured protective factors.Frailty transitions over 2 years were analyzed prospectively.Pearson’s correlation examined the relationship between FI and PI,and logistic regression assessed the effects of PI on frailty transitions.Results This study included 9,093 older adults.FI values increased with age and were higher in women,whereas PI values decreased with age and were higher in men.Over 2 years,56.2%of the participants showed a stable frailty status,14.2%improved,and 29.6%worsened.Negative transitions were more common than positive transitions,with transitions occurring most frequently between adjacent states.The PI was moderately negatively correlated with the FI(r=−0.349,P<0.001).A higher PI was associated with a lower risk of negative transitions among robust and prefrail individuals(OR=0.989,0.981,both P<0.05),but showed no significant effect among those with existing frailty.Conclusion Negative frailty transitions were more common with advancing age.Enhancing PI may help prevent negative frailty transitions among robust and pre-frail older adults,underscoring the value of early interventions.展开更多
Background:Low relative sit-to-stand(STS)power has emerged as a critical predictor of adverse health outcomes,such as frailty and disability,in older adults.However,its impact on falls,fractures,hospitalizations,and a...Background:Low relative sit-to-stand(STS)power has emerged as a critical predictor of adverse health outcomes,such as frailty and disability,in older adults.However,its impact on falls,fractures,hospitalizations,and all-cause mortality remains unclear.Therefore,this longitudinal study aimed to investigate the potential associations between low relative STS power and these adverse health outcomes in older adults.Methods:A total of 1876 older adults(aged≥65 years,56.4%women)were included from the Toledo Study for Healthy Aging.Relative STS power was assessed using the 30-s STS test and the Alcazar equation.Participants were categorized as having low relative STS power based on previously established cut-off points(2.53 W/kg for men and 2.01 W/kg for women).Falls and fractures(hip and all-type)within the previous year were recorded.Hospitalizations and all-cause mortality were obtained during a follow-up of 6.8±3.1 years(mean±SD;median=7.8 years;interquartile range:3.9-10.1 years)and 9.7±3.5 years(median=10.9 years;interquartile range:8.2-12.5 years),respectively.Generalized linear mixed models,binary logistic regression,and proportional hazards regression adjusted for age,educational level,and comorbidities were used.Results:In men,low relative STS power was significantly associated with an increased likelihood of history of falls(odds ratio(OR)=1.73,95%confidence interval(95%CI):1.08-2.75,p=0.022)and all-type fractures(OR=1.86,95%CI:1.21-2.84,p=0.004)in the previous year.In women,low relative STS power was associated with a higher probability of hip fractures within the previous year(OR=3.25,95%CI:1.07-9.86,p=0.038).Low relative STS power predicted hospitalizations in women(hazard ratio(HR)=1.29,95%CI:1.06-1.58,p=0.012)and longer hospital stays in both men(p=0.020)and women(p=0.033).Low relative STS power significantly increased all-cause mortality in both men(HR=1.57,95%CI:1.26-1.97,p<0.001)and women(HR=2.04,95%CI:1.51-2.74,p<0.001).Conclusion:Low relative STS power was associated with history of hip fractures in women,whereas in men it was associated with history of falls and all-type fractures.Low relative STS power predicted hospitalizations in women but not in men.In both men and women,low relative STS power was associated with longer hospital stays and increased risk of all-cause mortality.展开更多
Addiction,a complex and chronic neurobiological disorder,is characterized by compulsive substance use despite harmful consequences,leading to persistent alterations in brain function,particularly within the reward,mot...Addiction,a complex and chronic neurobiological disorder,is characterized by compulsive substance use despite harmful consequences,leading to persistent alterations in brain function,particularly within the reward,motivation,and decision-making systems.Despite the availability of a range of treatment options,including pharmacotherapy and behavioral therapies,relapse remains a major challenge,with many individuals struggling to maintain long-term recovery.Current treatments often show limited efficacy,underscoring the need for novel therapeutic strategies that can address the underlying neurobiological disruptions in addiction.展开更多
BACKGROUND The previous studies have primarily focused on the influence of botulinum toxin A(BoNT-A)injection on emotions during the period of peak motor symptom improvement in blepharospasm patients,based on facial f...BACKGROUND The previous studies have primarily focused on the influence of botulinum toxin A(BoNT-A)injection on emotions during the period of peak motor symptom improvement in blepharospasm patients,based on facial feedback hypothesis.AIM To evaluate the sustained anxiolytic and antidepressant effects of BoNT-A in blepharospasm patients beyond motor symptom control.METHODS We recruited benign essential blepharospasm patients with BoNT-A treatment and collected their data to compare scale scores of Jankovic Rating Scale,Blepharospasm Disability Index,Self-rating Anxiety Scale(SAS),Self-rating Depression Scale(SDS),Hamilton Anxiety Scale and Hamilton Depression Scale between pretreatment(baseline)and pre-reinjection(treatment),to further assess the effects of repeated treatments with BoNT by using sub-group analyses in the certain special states.RESULTS A total of 21 eligible blepharospasm patients were with the mean age of 58.4 years and a male-to-female ratio of 1:6.Significantly decreases in the subscale scores of SDS and SAS,including SDS well-being index,decreased capacity and hard to decide,SAS inability to sit still and headache were showed at post-a single BoNT-A injection when scale scores of Jankovic Rating Scale and Blepharospasm Disability Index were matched between baseline and posttreatment.With each additional BoNT-A injection,the odds ratio of patients with the moderate depressive symptoms decreased by 92.6%.Moreover,BoNT treatment remained a decrease in the subscale scores of SDS and SAS in patients with repeated injections.CONCLUSION This study is to demonstrate that repeated BoNT-A injection have a long-lasting relief for anxiety and depressive symptoms in blepharospasm even after its motor symptom-modulating effects have diminished.展开更多
Penetrance is a crucial indicator for accurately assessing disease risk and plays a vital role in disease research,gene therapy,and genetic counseling.However,with penetrance data dispersed across various sources,effi...Penetrance is a crucial indicator for accurately assessing disease risk and plays a vital role in disease research,gene therapy,and genetic counseling.However,with penetrance data dispersed across various sources,efficiently accessing and consolidating this information becomes a challenge.A comprehensive platform that integrates penetrance is urgently needed.Here,we present PenCards,a global,community-contributed public archive of variant penetrance,by first collecting penetrance data from all published literature and then using large international cohorts to specifically calculate the penetrance of autism-related variants.PenCards contains a total of 244,531 variants,including 239,244 single nucleotide variants,4994 insertions and deletions,and 293 copy number variants,covering approximately 300 phenotypes.We also provide a submission portal for the dynamic updating of penetrance.Additionally,to help users efficiently access genetic information,we comprehensively integrate over 150 variant-and gene-level resources.In summary,PenCards is a powerful platform designed to advance genetic research and diagnostics.PenCards is publicly available at https://genemed.tech/pencards/.展开更多
Monocytes play a crucial role in post-stroke immune infiltration,yet the intricate immune regulatory networks they orchestrate in ischemic stroke remain poorly understood.This knowledge gap has hindered the developmen...Monocytes play a crucial role in post-stroke immune infiltration,yet the intricate immune regulatory networks they orchestrate in ischemic stroke remain poorly understood.This knowledge gap has hindered the development of targeted monocyte-based therapies for stroke.Here,we used a multi-omics approach combining single-cell and bulk transcriptomics.CellChat analysis revealed intercellular communication networks,while key genes were identified and predictive models built through Lasso regression.Immune cell infiltration dynamics were quantified using single-sample gene set enrichment analysis.Gene set enrichment analysis and gene set variation analysis identified disease-regulated pathways of core genes.MicroRNA networks and transcription factors were investigated using mircode and RcisTarget.Experimental validation was performed using oxygen-glucose deprivation and transient middle cerebral artery occlusion models,focusing on the influence of abhydrolase domain-containing protein 2 on monocyte function.We observed significantly elevated monocyte content in stroke brain tissue samples,and identified key monocyte genes associated with immune inflammation,chemokine signaling,and cell receptor function.A robust seven-gene predictive model for ischemic stroke was developed.CD274 strongly correlated with these seven genes,suggesting a potential immunomodulatory axis.In vivo transient middle cerebral artery occlusion experiments validated the predictive value of key genes.In vitro studies demonstrated that abhydrolase domain-containing protein 2 overexpression enhanced monocyte proliferation and phagocytic activity post-oxygen-glucose deprivation while reducing reactive oxygen species generation.In conclusion,this study maps post-stroke monocyte communication networks,identifies key signaling pathways,identifies regulatory mechanisms,and validates the functional importance of key genes,particularly abhydrolase domain-containing protein 2.These findings provide a foundation for developing targeted immunomodulatory therapies and precision diagnostics in ischemic stroke management.展开更多
Tendon-related diseases(TRDs)are increasingly common in the current aging society and impose a significant burden on patients.Despite therapeutic advances,the pathophysiology of TRDs remains poorly understood,hinderin...Tendon-related diseases(TRDs)are increasingly common in the current aging society and impose a significant burden on patients.Despite therapeutic advances,the pathophysiology of TRDs remains poorly understood,hindering effective clinical management.The macrophages are highly plastic immune cells involved in the maintenance of in vivo homeostasis and the injury-healing process.Their dual role in TRDs has been widely investigated,either promoting tenogenic and chondrogenic differentiation or amplifying inflammatory response,underscoring their therapeutic potential for TRDs treatment.Therefore,the review aims to summarize the roles of macrophages in the healing of TRDs,characterized by limited regenerative capacity,and examine strategies for the modulation of macrophage phenotypes to accelerate the regeneration process.Finally,we review applications involving macrophage modulation within the context of tissue engineering of TRDs,providing novel insights for the design of biomaterials-based targeted delivery systems.展开更多
Objective:To investigate the effect of pectic polysaccharides isolated from Rauvolfia verticillata on ulcerative colitis and its underlying mechanisms.Methods:Pectic polysaccharides were characterized using high-perfo...Objective:To investigate the effect of pectic polysaccharides isolated from Rauvolfia verticillata on ulcerative colitis and its underlying mechanisms.Methods:Pectic polysaccharides were characterized using high-performance liquid chromatography with 1-phenyl-3-methyl-5-pyrazolone pre-column derivatization,phenol-sulfuric acid assay,and gel permeation chromatography.HT-29 cells were stimulated with lipopolysaccharide and then treated with pectic polysaccharides;conditioned medium was applied to THP-1-derived macrophages to assess cell viability and polarization,while tight junction protein expression was analyzed in HT-29 cells.Furthermore,a mouse model of dextran sulfate sodium-induced colitis was treated with oral pectic polysaccharides or NOS2 overexpression.Body weight,disease activity index,colon length,histopathology,and the protein expression related to the JAK2/STAT3-NOS2 signaling were evaluated.Results:The pectic polysaccharide was characterized as an acidic pectic polysaccharide,primarily composed of galacturonic acid and various neutral sugars,with a narrow molecular weight distribution and high purity.Pectic polysaccharides significantly enhanced THP-1 macrophage viability,promoted M1 to M2 polarization,and upregulated the expression of epithelial tight junction proteins.In addition,pectic polysaccharide treatment attenuated body weight loss,lowered disease activity index scores and improved colon histology in mice with dextran sulfate sodium-induced colitis.It also reduced JAK2/STAT3 phosphorylation and NOS2 expression,and increased the expression of tight junction proteins(ZO-1,occludin,and claudin-1).Conclusions:Pectic polysaccharides attenuate ulcerative colitis by increasing M2-related macrophage markers,inhibiting the JAK2/STAT3-NOS2 signaling,and enhancing epithelial barrier-related protein expression.These findings support pectic polysaccharides as a natural candidate for the treatment of ulcerative colitis.展开更多
Alzheimer’s disease,a devastating neurodegenerative disorder,is characterized by progressive cognitive decline,primarily due to amyloid-beta protein deposition and tau protein phosphorylation.Effectively reducing the...Alzheimer’s disease,a devastating neurodegenerative disorder,is characterized by progressive cognitive decline,primarily due to amyloid-beta protein deposition and tau protein phosphorylation.Effectively reducing the cytotoxicity of amyloid-beta42 aggregates and tau oligomers may help slow the progression of Alzheimer’s disease.Conventional drugs,such as donepezil,can only alleviate symptoms and are not able to prevent the underlying pathological processes or cognitive decline.Currently,active and passive immunotherapies targeting amyloid-beta and tau have shown some efficacy in mice with asymptomatic Alzheimer’s disease and other transgenic animal models,attracting considerable attention.However,the clinical application of these immunotherapies demonstrated only limited efficacy before the discovery of lecanemab and donanemab.This review first discusses the advancements in the pathogenesis of Alzheimer’s disease and active and passive immunotherapies targeting amyloid-beta and tau proteins.Furthermore,it reviews the advantages and disadvantages of various immunotherapies and considers their future prospects.Although some antibodies have shown promise in patients with mild Alzheimer’s disease,substantial clinical data are still lacking to validate their effectiveness in individuals with moderate Alzheimer’s disease.展开更多
文摘As a critical department ensuring the sterility of hospital instruments,the Sterile Supply Center(SSC)directly impacts the sterility status of clinical instruments through its sterilization qualification rate.Geriatric patients,due to physiological decline and compromised immune function,constitute a high-risk group for hospital-acquired infections,with more stringent requirements for instrument sterility.This paper analyzes the current status and influencing factors of sterilization qualification rates in SSCs,explores the mechanistic association between sterilization qualification rates and infections in geriatric departments,and proposes targeted strategies to improve sterilization qualification rates.It highlights the pivotal role of SSC instrument sterilization in infection prevention and control for geriatric patients,providing theoretical basis and practical guidance for optimizing SSC management,reducing infection rates in geriatric departments,and ensuring the safety of elderly patients’medical care.These findings aim to enhance overall infection management standards in hospitals.
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 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Brain insulin resistance(BIR)is a prevalent detrimental feature of Alzheimer’s disease(AD)and all-cause dementia.Therapies designed to activate insulin signaling and enhance insulin receptor sensitivity have proven beneficial for cognitive enhancement in pre-clinical models,non-human primates,and humans.BIR encompasses dysregulated brain insulin signaling,which is either due to insulin receptor resistance,reduced insulin receptor levels,or reduced levels of insulin in the brain,affecting processes involved in AD development and progression.
基金National Key Research and Development Program of China,Grant/Award Number:2021YFF0702200Science and Technology Projects in Guangzhou,Grant/Award Number:202206010084,202206010197 and 202206060002+1 种基金Guangdong S&T programme,Grant/Award Number:2009A081000002 and 2023B0303040004Technology Planning Project of Linzhi,Grant/Award Number:2023-YZ-01。
文摘Background:The aim of the study was to develop a non-human primate model of metabolic dysfunction in Macaca fascicularis using chronic high-fat diet(HFD)to mimic clinical disease progression.Methods:Thirty-five male macaques aged 10-15 years underwent an 18-month HFD intervention.Physiological parameters(BMI,BP,hematology),liver fat fraction(evaluated by ultrasound/MRI),cardiac function(assessed by echocardiography),and histopathology(using liver biopsy)were measured before and after the intervention.Serum proteomics with KEGG/STRING analyses identified molecular mechanisms.Results:Within 6 months,HFD induced dyslipidemia(elevated TG,TCHO,HDL-C,LDL-C).After 18 months,metabolic dysfunction-associated steatohepatitis(MASH)was confirmed by histopathology in 57.14%(16/28)of macaques,diabetes(elevated FPG/HbA1c)in 17.86%(5/28),and myocardial hypertrophy(elevated LVMass/LAD)in 46.43%(13/28).Proteomics identified Bile acid-CoA:amino acid N-acyltransferase(BAAT)as a MASH hallmark protein,the level of which was inversely correlated with the degree of fibrosis.For diabetes,citrate synthase(CS)and malate dehydrogenase 1(MDH1)impaired glucose oxidation via the TCA cycle,while hexose-6-phosphate de-hydrogenase(H6PD)disrupted gluconeogenesis.Myocardial hypertrophy was associ-ated with the downregulation of SRC proto-oncogene,non-receptor tyrosine kinase(SRC),mitogen-activated protein kinase 14(MAPK14),emerin(EMD),and integrin subunit beta 1(ITGB1).Conclusions:An 18-month HFD successfully established a translational M.fascicula-ris model replicating key metabolic disorders(MASH,diabetes,cardiac hypertrophy).BAAT,CS/MDH1/H6PD,and SRC/MAPK14/EMD/ITGB1 were identified as mecha-nistic biomarkers for these conditions.
文摘Mitophagy is a well-characterized and redundant recycling system for damaged mitochondria and a marker of organelle quality(Picca et al.,2023).Yet,the assessment of mitophagy in vivo remains a challenge.The characterization of the endosomallysosomal pathways supporting the endocytic tra fficking has provided invaluable information also into mitophagy signaling.
文摘Sarcopenia in the elderly is a syndrome characterized by age-related progressive loss of muscle mass, decline in muscle strength, and deterioration of muscle function. Its high incidence significantly increases the risk of falls, fractures, disability, and mortality among the elderly, posing a global public health challenge for geriatric health. Insulin-like growth factor-1 (IGF-1), a key cytokine regulating muscle growth, repair, and metabolism, exhibits a progressive decline in serum levels with aging and is closely associated with the onset and progression of sarcopenia in the elderly. This study reviews the research progress of IGF-1 in the diagnosis and efficacy prediction of sarcopenia in the elderly, providing theoretical references for precise diagnosis, treatment, and prognosis assessment of sarcopenia in the elderly.
基金supported by the National Natural Science Foundation of China(82271401,82071394)the Tianjin Health Research Project(TJWJ2024RC002)。
文摘Background:Repetitive mild traumatic brain injury(rmTBI)is a significant risk factor for neurodegeneration,characterized by pathological protein deposition and persistent neuroinflammation.Research has observed increased interleukin-33(IL-33)levels in the peripheral blood of patients with rmTBI,suggesting IL-33 may participate in regulating the pathological development of rmTBI.The study aims to elucidate the impact and mechanism of IL-33 in the progression of neuropathology following rmTBI,and to explore its potential as a therapeutic target to improve the neurological outcome.Methods:The study employed an rmTBI mouse model using the wild-type(WT)and IL-33 knockout mice.Cognitive function was assessed via the Y-maze and Barnes tests.The main cell type expressing IL-33 and its receptor,suppression of tumorigenicity 2(ST2),was then investigated in the mouse brain through immunofluorescence colocalization.As the primary neural cell responsible for ST2 expression,microglia were studied in vitro using the BV2 cell line.The effects of lipid droplets(LDs)accumulation and amyloid-beta(Aβ)phagocytosis were measured to elucidate the impact of IL-33 on BV2 cells'phagocytosis.Additionally,HT22 neuronal apoptosis was assessed by flow cytometry.Finally,the cognitive effects of intranasal administration of IL-33 were evaluated in mice.Results:IL-33 KO mice exhibited pronounced cognitive impairment after rmTBI.In the mouse brain,astrocytes were identified as the primary source of IL-33 secretion,while microglia predominantly expressed ST2.Transcriptome sequencing revealed that IL-33 significantly influenced phagocytosis function.IL-33 mitigated LDs accumulation in BV2 cells and enhanced Aβphagocytosis in vitro.In addition,the culture medium of BV2 cells with activated IL-33/ST2 signaling reduced HT22 neuronal apoptosis and axonal damage.Furthermore,intranasal administration of IL-33 was observed to be effective in alleviating neurodegeneration and cognitive outcome of rmTBI mice.Conclusions:Dysfunction of the IL-33/ST2 axis following rmTBI leads to cognitive dysfunction via impairing microglial phagocytosis capacity and promoting neuronal damage.IL-33 would be a promising therapeutic target for alleviating neurodegeneration following rmTBI.
基金supported by the Youth Program of the National Natural Science Foundation of China,Nos.81901282(to XC),82101326(to WG),81870992(to PX),and 81870856the Guangdong Basic and Applied Basic Research Foundation of the Science Foundation,Nos.2024A1515012919(to XC)and 2019A1515011189(to XC)+5 种基金the Central Government Guiding Local Science and Technology Development Projects,No.ZYYD2022C17(to PX)the Key Project of the Guangzhou Health Commission,No.2019-ZD-09(to PX)the Basic and Applied Basic Research of the City and School Jointly Funded Projects,No.20220102397(to QL)the Guangdong College Students Innovation and Entrepreneurship Training Program,No.S202310570017(to WY)the Science and Technology Planning Project of Guangzhou,Nos.2023B03J0631(to PX),2024A03J1152(to XC),and 202102010010(to PX)the Basic Research Program of the Guangzhou Science and Technology Bureau Jointly-funded Dengfeng Hospital Project,No.20232031(to XC).
文摘Parkinson’s disease is the second most common neurodegenerative disorder.ATPase H+transporting V0 subunit A1(ATP6V0A1)is a component of vacuolar H+-ATPase(V-ATPase),an ATP-dependent proton pump.Our previous research identified an association between the ATP6V0A1 rs601999 variant and Parkinson’s disease;however,the underlying mechanisms of ATP6V0A1 in Parkinson’s disease remain elusive.In this study,we generated ATP6V0A1 knockdown and overexpression models and then examined the degeneration of dopaminergic neurons,lysosomal function,and the autophagy-lysosomal pathway using immunohistochemistry,western blotting,and transmission electron microscopy.We found that ATP6V0A1 protected against lysosomal dysfunction,regulated autophagic flux,and decreased phosphorylatedα-synuclein levels in vitro.In vivo,ATP6V0A1 reduced levels ofα-synuclein and phosphorylatedα-synuclein proteins,mitigated degeneration of dopaminergic neurons,and improved motor dysfunction.Collectively,these findings show that ATP6V0A1 plays a protective role in Parkinson’s disease by modulating the autophagy-lysosomal pathway.A correlation between ATP6V0A1 and Parkinson’s disease susceptibility may serve as a biomarker for Parkinson’s disease,while the protective effects of ATP6V0A1 could represent a potential therapeutic target for the disease.
基金supported by grants from the National Key R&D Program of China[Grant Nos.2020YFC2003000 and 2020YFC2003001]the National High Level Hospital Clinical Research Funding(BJ-2023-074 and BJ-2023-018)+1 种基金Beijing Municipal Science&Technology Commission“AI+Health Collaborative Innovation Cultivation”Project(Z221100003522015)the Non-Profit Central Research Institute Fund of the Chinese Academy of Medical Sciences(2021-JKCS-024).
文摘Objective Frailty is becoming increasingly common among aging adults.Frailty transitionis shaped by biological,social,psychological,and environmental factors.This study investigated combined effects of protective factors on frailty transition by constructing a Protection Index(PI)to guide targeted interventions.Methods Data were extracted from the 4th Sample Survey of the Aged Population in Urban and Rural China,including baseline(2017)and follow-up(2019)surveys.Frailty was assessed using the Frailty Index(FI),whereas the PI measured protective factors.Frailty transitions over 2 years were analyzed prospectively.Pearson’s correlation examined the relationship between FI and PI,and logistic regression assessed the effects of PI on frailty transitions.Results This study included 9,093 older adults.FI values increased with age and were higher in women,whereas PI values decreased with age and were higher in men.Over 2 years,56.2%of the participants showed a stable frailty status,14.2%improved,and 29.6%worsened.Negative transitions were more common than positive transitions,with transitions occurring most frequently between adjacent states.The PI was moderately negatively correlated with the FI(r=−0.349,P<0.001).A higher PI was associated with a lower risk of negative transitions among robust and prefrail individuals(OR=0.989,0.981,both P<0.05),but showed no significant effect among those with existing frailty.Conclusion Negative frailty transitions were more common with advancing age.Enhancing PI may help prevent negative frailty transitions among robust and pre-frail older adults,underscoring the value of early interventions.
基金supported by Centro de Investigaci on Biom edica en Red Fragilidad y Envejecimiento Saludable(CIBERFES)(Grant Nos.CB16/10/00477,CB16/10/00456,and CB16/10/00464)Plan Propio de Investigaci on of the University of Castilla-La Mancha,and Fondo Europeo de Desarrollo Regional(FEDER)funds from the European Union(Grant No.2022-GRIN-34296)+3 种基金further funded by grants from the Instituto de Salud Carlos III(Grant Nos.PI031558,PI07/90637,PI07/90306,RD 06/0013,and PI18/00972)the Government of Castilla-La Mancha(Grant Nos.03031 and SBPLY/19/180501/000312)Red EXERNETRED DE EJERCICIO FISICO Y SALUD:RED2022-134800T from the Spanish Ministry of Innovation and Sciencesupported by a research grant from the University of Castilla-La Mancha(Programa Investigo,Grant No.2024INVGO-12359)。
文摘Background:Low relative sit-to-stand(STS)power has emerged as a critical predictor of adverse health outcomes,such as frailty and disability,in older adults.However,its impact on falls,fractures,hospitalizations,and all-cause mortality remains unclear.Therefore,this longitudinal study aimed to investigate the potential associations between low relative STS power and these adverse health outcomes in older adults.Methods:A total of 1876 older adults(aged≥65 years,56.4%women)were included from the Toledo Study for Healthy Aging.Relative STS power was assessed using the 30-s STS test and the Alcazar equation.Participants were categorized as having low relative STS power based on previously established cut-off points(2.53 W/kg for men and 2.01 W/kg for women).Falls and fractures(hip and all-type)within the previous year were recorded.Hospitalizations and all-cause mortality were obtained during a follow-up of 6.8±3.1 years(mean±SD;median=7.8 years;interquartile range:3.9-10.1 years)and 9.7±3.5 years(median=10.9 years;interquartile range:8.2-12.5 years),respectively.Generalized linear mixed models,binary logistic regression,and proportional hazards regression adjusted for age,educational level,and comorbidities were used.Results:In men,low relative STS power was significantly associated with an increased likelihood of history of falls(odds ratio(OR)=1.73,95%confidence interval(95%CI):1.08-2.75,p=0.022)and all-type fractures(OR=1.86,95%CI:1.21-2.84,p=0.004)in the previous year.In women,low relative STS power was associated with a higher probability of hip fractures within the previous year(OR=3.25,95%CI:1.07-9.86,p=0.038).Low relative STS power predicted hospitalizations in women(hazard ratio(HR)=1.29,95%CI:1.06-1.58,p=0.012)and longer hospital stays in both men(p=0.020)and women(p=0.033).Low relative STS power significantly increased all-cause mortality in both men(HR=1.57,95%CI:1.26-1.97,p<0.001)and women(HR=2.04,95%CI:1.51-2.74,p<0.001).Conclusion:Low relative STS power was associated with history of hip fractures in women,whereas in men it was associated with history of falls and all-type fractures.Low relative STS power predicted hospitalizations in women but not in men.In both men and women,low relative STS power was associated with longer hospital stays and increased risk of all-cause mortality.
基金supported by the National Natural Science Foundation of China(T2350008)the STI2030-Major Projects[2021ZD0203000(2021ZD0203003)]the Open Research Fund of the State Key Laboratory of Brain-Machine Intelligence,Zhejiang University(BMI2400014).
文摘Addiction,a complex and chronic neurobiological disorder,is characterized by compulsive substance use despite harmful consequences,leading to persistent alterations in brain function,particularly within the reward,motivation,and decision-making systems.Despite the availability of a range of treatment options,including pharmacotherapy and behavioral therapies,relapse remains a major challenge,with many individuals struggling to maintain long-term recovery.Current treatments often show limited efficacy,underscoring the need for novel therapeutic strategies that can address the underlying neurobiological disruptions in addiction.
基金Supported by the Special Funds of Jiangsu Provincial Key Research and Development Projects,No.BE2019612Scientific Research Project Cooperated by Lanzhou Biotechnology Development Co.,Ltd.+3 种基金the Key R&D Program of Jiangsu Science and Technology Project,No.BE2022049 and No.BE2022049-1National Natural Science Foundation of China,No.82171249Nanjing Rehabilitation Medicine Center ProjectJiangsu Provincial Health Commission Special Fund for Aging and Health.
文摘BACKGROUND The previous studies have primarily focused on the influence of botulinum toxin A(BoNT-A)injection on emotions during the period of peak motor symptom improvement in blepharospasm patients,based on facial feedback hypothesis.AIM To evaluate the sustained anxiolytic and antidepressant effects of BoNT-A in blepharospasm patients beyond motor symptom control.METHODS We recruited benign essential blepharospasm patients with BoNT-A treatment and collected their data to compare scale scores of Jankovic Rating Scale,Blepharospasm Disability Index,Self-rating Anxiety Scale(SAS),Self-rating Depression Scale(SDS),Hamilton Anxiety Scale and Hamilton Depression Scale between pretreatment(baseline)and pre-reinjection(treatment),to further assess the effects of repeated treatments with BoNT by using sub-group analyses in the certain special states.RESULTS A total of 21 eligible blepharospasm patients were with the mean age of 58.4 years and a male-to-female ratio of 1:6.Significantly decreases in the subscale scores of SDS and SAS,including SDS well-being index,decreased capacity and hard to decide,SAS inability to sit still and headache were showed at post-a single BoNT-A injection when scale scores of Jankovic Rating Scale and Blepharospasm Disability Index were matched between baseline and posttreatment.With each additional BoNT-A injection,the odds ratio of patients with the moderate depressive symptoms decreased by 92.6%.Moreover,BoNT treatment remained a decrease in the subscale scores of SDS and SAS in patients with repeated injections.CONCLUSION This study is to demonstrate that repeated BoNT-A injection have a long-lasting relief for anxiety and depressive symptoms in blepharospasm even after its motor symptom-modulating effects have diminished.
基金supported by the National Natural Science Foundation of China(32070591,82371552,and W2512102)the Scientific Research Program of FuRong Laboratory(2023SK2093-1)+2 种基金the Central South University Research Programme of Advanced Interdisciplinary Study(2023QYJC010)the Natural Science Foundation of Hunan Province(2023JJ30975)the Fundamental Research Funds for the Central Universities of Central South University(2025ZZTS0834).
文摘Penetrance is a crucial indicator for accurately assessing disease risk and plays a vital role in disease research,gene therapy,and genetic counseling.However,with penetrance data dispersed across various sources,efficiently accessing and consolidating this information becomes a challenge.A comprehensive platform that integrates penetrance is urgently needed.Here,we present PenCards,a global,community-contributed public archive of variant penetrance,by first collecting penetrance data from all published literature and then using large international cohorts to specifically calculate the penetrance of autism-related variants.PenCards contains a total of 244,531 variants,including 239,244 single nucleotide variants,4994 insertions and deletions,and 293 copy number variants,covering approximately 300 phenotypes.We also provide a submission portal for the dynamic updating of penetrance.Additionally,to help users efficiently access genetic information,we comprehensively integrate over 150 variant-and gene-level resources.In summary,PenCards is a powerful platform designed to advance genetic research and diagnostics.PenCards is publicly available at https://genemed.tech/pencards/.
基金National Natural Science Foundation of China,No.82471361(to MZ)the Natural Science Foundation for Excellent Young Scholars of Hunan Province,No.2021JJ20095(to MZ)+3 种基金the Key Research and Development Program of Hunan Province,No.2020SK2063(to MZ)the Research Project on Education and Teaching Innovation of Central South University,No.2021jy145(to MZ)the Natural Science Foundations of Hunan Province,No.2020JJ4134(to MZ)the Fundamental Research Funds for the Central Universities of Central South University,No.2023ZZTS0595(to YP).
文摘Monocytes play a crucial role in post-stroke immune infiltration,yet the intricate immune regulatory networks they orchestrate in ischemic stroke remain poorly understood.This knowledge gap has hindered the development of targeted monocyte-based therapies for stroke.Here,we used a multi-omics approach combining single-cell and bulk transcriptomics.CellChat analysis revealed intercellular communication networks,while key genes were identified and predictive models built through Lasso regression.Immune cell infiltration dynamics were quantified using single-sample gene set enrichment analysis.Gene set enrichment analysis and gene set variation analysis identified disease-regulated pathways of core genes.MicroRNA networks and transcription factors were investigated using mircode and RcisTarget.Experimental validation was performed using oxygen-glucose deprivation and transient middle cerebral artery occlusion models,focusing on the influence of abhydrolase domain-containing protein 2 on monocyte function.We observed significantly elevated monocyte content in stroke brain tissue samples,and identified key monocyte genes associated with immune inflammation,chemokine signaling,and cell receptor function.A robust seven-gene predictive model for ischemic stroke was developed.CD274 strongly correlated with these seven genes,suggesting a potential immunomodulatory axis.In vivo transient middle cerebral artery occlusion experiments validated the predictive value of key genes.In vitro studies demonstrated that abhydrolase domain-containing protein 2 overexpression enhanced monocyte proliferation and phagocytic activity post-oxygen-glucose deprivation while reducing reactive oxygen species generation.In conclusion,this study maps post-stroke monocyte communication networks,identifies key signaling pathways,identifies regulatory mechanisms,and validates the functional importance of key genes,particularly abhydrolase domain-containing protein 2.These findings provide a foundation for developing targeted immunomodulatory therapies and precision diagnostics in ischemic stroke management.
基金supported by the Guangxi Natural Science Foundation(AD21220065 to JX)the National Natural Science Foundation of China(82102632 and 82160412 to JX)the Guangdong Basic and Applied Basic Research Foundation(2023A1515220072 to ZHD)。
文摘Tendon-related diseases(TRDs)are increasingly common in the current aging society and impose a significant burden on patients.Despite therapeutic advances,the pathophysiology of TRDs remains poorly understood,hindering effective clinical management.The macrophages are highly plastic immune cells involved in the maintenance of in vivo homeostasis and the injury-healing process.Their dual role in TRDs has been widely investigated,either promoting tenogenic and chondrogenic differentiation or amplifying inflammatory response,underscoring their therapeutic potential for TRDs treatment.Therefore,the review aims to summarize the roles of macrophages in the healing of TRDs,characterized by limited regenerative capacity,and examine strategies for the modulation of macrophage phenotypes to accelerate the regeneration process.Finally,we review applications involving macrophage modulation within the context of tissue engineering of TRDs,providing novel insights for the design of biomaterials-based targeted delivery systems.
基金supported by the Key Research and Development Project of Hainan Province(ZDYF2022SHFZ099)the Academic Enhancement Support Program of Hainan Medical University(XSTS2025040 and XSTS2025063).
文摘Objective:To investigate the effect of pectic polysaccharides isolated from Rauvolfia verticillata on ulcerative colitis and its underlying mechanisms.Methods:Pectic polysaccharides were characterized using high-performance liquid chromatography with 1-phenyl-3-methyl-5-pyrazolone pre-column derivatization,phenol-sulfuric acid assay,and gel permeation chromatography.HT-29 cells were stimulated with lipopolysaccharide and then treated with pectic polysaccharides;conditioned medium was applied to THP-1-derived macrophages to assess cell viability and polarization,while tight junction protein expression was analyzed in HT-29 cells.Furthermore,a mouse model of dextran sulfate sodium-induced colitis was treated with oral pectic polysaccharides or NOS2 overexpression.Body weight,disease activity index,colon length,histopathology,and the protein expression related to the JAK2/STAT3-NOS2 signaling were evaluated.Results:The pectic polysaccharide was characterized as an acidic pectic polysaccharide,primarily composed of galacturonic acid and various neutral sugars,with a narrow molecular weight distribution and high purity.Pectic polysaccharides significantly enhanced THP-1 macrophage viability,promoted M1 to M2 polarization,and upregulated the expression of epithelial tight junction proteins.In addition,pectic polysaccharide treatment attenuated body weight loss,lowered disease activity index scores and improved colon histology in mice with dextran sulfate sodium-induced colitis.It also reduced JAK2/STAT3 phosphorylation and NOS2 expression,and increased the expression of tight junction proteins(ZO-1,occludin,and claudin-1).Conclusions:Pectic polysaccharides attenuate ulcerative colitis by increasing M2-related macrophage markers,inhibiting the JAK2/STAT3-NOS2 signaling,and enhancing epithelial barrier-related protein expression.These findings support pectic polysaccharides as a natural candidate for the treatment of ulcerative colitis.
基金supported by the Nature Science Foundation of Liaoning Province,Nos.2022-MS-211,2021-MS-064,and 2024-MS-048(all to YC).
文摘Alzheimer’s disease,a devastating neurodegenerative disorder,is characterized by progressive cognitive decline,primarily due to amyloid-beta protein deposition and tau protein phosphorylation.Effectively reducing the cytotoxicity of amyloid-beta42 aggregates and tau oligomers may help slow the progression of Alzheimer’s disease.Conventional drugs,such as donepezil,can only alleviate symptoms and are not able to prevent the underlying pathological processes or cognitive decline.Currently,active and passive immunotherapies targeting amyloid-beta and tau have shown some efficacy in mice with asymptomatic Alzheimer’s disease and other transgenic animal models,attracting considerable attention.However,the clinical application of these immunotherapies demonstrated only limited efficacy before the discovery of lecanemab and donanemab.This review first discusses the advancements in the pathogenesis of Alzheimer’s disease and active and passive immunotherapies targeting amyloid-beta and tau proteins.Furthermore,it reviews the advantages and disadvantages of various immunotherapies and considers their future prospects.Although some antibodies have shown promise in patients with mild Alzheimer’s disease,substantial clinical data are still lacking to validate their effectiveness in individuals with moderate Alzheimer’s disease.
