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
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
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
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
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
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
Driven by rapid global population growth and evolving consumer demands for high-quality nutrition and enhanced sensory enjoyment,the food industry is advancing towards healthier,more efficient,more sustainable,and mor...Driven by rapid global population growth and evolving consumer demands for high-quality nutrition and enhanced sensory enjoyment,the food industry is advancing towards healthier,more efficient,more sustainable,and more personalized targets.Notably,this transformation is being accelerated by the convergence of advanced biotechnology(BT)and information technology(IT)in food production systems.This review examines pivotal technologies shaping future food systems,highlighting two biotechnological frontiers and two artificial intelligence-driven domains.Specifically,evolutionary engineering enhances microbial resilience and production efficiency while synthetic biology expands the diversity of food sources and enables personalized food ingredient design,both of which advance sustainable food production.Meanwhile,artificial intelligence promotes food flavor innovation by integrating existing knowledge in molecular structure,flavoromics and consumer preferences.Furthermore,insights into gut microbiota,along with the development of omics techniques and wearable biosensors are unlocking attainable solutions for precision nutrition.Collectively,the trilateral convergence of BT,IT and food technology,embodying a harmonious balance,is reshaping the paradigm of future food manufacturing.展开更多
Objective To examine national trends in antibiotic consumption and antimicrobial resistance(AMR)among six WHO-priority bacterial pathogens in China from 2016 to 2022.Methods This ecological study analyzed national and...Objective To examine national trends in antibiotic consumption and antimicrobial resistance(AMR)among six WHO-priority bacterial pathogens in China from 2016 to 2022.Methods This ecological study analyzed national and provincial data from the China Antibacterial Resistance Surveillance System(CARSS)and the National Hospital Information Network.Beta regression models assessed temporal trends,and hierarchical models evaluated associations between antibiotic use and resistance.Results From 2016 to 2022,carbapenem resistance in Acinetobacter baumannii and Pseudomonas aeruginosa,and vancomycin resistance in Enterococcus faecium and E.faecalis significantly declined(β<0,P<0.010),while carbapenem-resistant Klebsiella pneumoniae increased(β=0.081,P<0.001).Nationwide antibiotic consumption rose across 10 major classes.Positive associations were found between carbapenem use and resistance in A.baumannii(z=2.719,P=0.007)and P.aeruginosa(z=3.241,P=0.001),and between vancomycin use and resistance in E.faecium(z=4.510,P=0.001)and E.faecalis(z=3.210,P=0.001).Conclusion Carbapenem-resistant K.pneumoniae increased significantly in China,while other resistant pathogens declined.Resistance patterns were linked to the use of multiple antibiotic classes,underscoring the need for strengthened antibiotic stewardship and surveillance.展开更多
BACKGROUND Post-endoscopic retrograde cholangiopancreatography pancreatitis(PEP)is a prevalent and potentially serious complication in patients undergoing endoscopic retrograde cholangiopancreatography.AIM To comprehe...BACKGROUND Post-endoscopic retrograde cholangiopancreatography pancreatitis(PEP)is a prevalent and potentially serious complication in patients undergoing endoscopic retrograde cholangiopancreatography.AIM To comprehensively assess the efficacy of indomethacin therapy in reducing PEP risk.METHODS We searched PubMed,EMBASE,Scopus,and Cochrane Library databases to identify randomized controlled trials(RCTs)that compared rectal indomethacin with a control group to prevent PEP.Duplicates were removed,and studies were included based on the established inclusion criteria.We used the Cochrane Collaboration’s tool to assess the risk of bias in the RCTs.A random-effects model was applied to produce pooled risk ratios(RRs)with 95%confidence intervals(CIs).RESULTS We included a total of 30 RCTs involving 16977 patients.Compared to the control group,rectal indomethacin showed comparable rates of overall PEP(PEP;RR=0.85,95%CI:0.69-1.04,I2=79%)with no statistically significant difference of RR in mild(RR=0.92,95%CI:0.74-1.14),moderate(RR=0.78,95%CI:0.59-1.02),or severe PEP(RR=1.12,95%CI:0.75-1.67).There was also no difference in cases of adverse events(RR=0.97,95%CI:0.69-1.35),abdominal pain(RR=1.14,95%CI:0.80-1.62),bleeding(RR=1.07,95%CI:0.70-1.63),or mortality(RR=0.86,95%CI:0.56-1.33)between the two groups.Subgroup analyses were also performed.CONCLUSION Rectal indomethacin appears to be safe and may offer benefit in selected high-risk patients,though findings should be interpreted with caution due to high heterogeneity.展开更多
Objective Previous Mendelian randomization(MR)studies have suggested an association between the gut microbiome and metabolic-associated fatty liver disease(MAFLD).However,the reliance on 16S rRNA sequencing data has l...Objective Previous Mendelian randomization(MR)studies have suggested an association between the gut microbiome and metabolic-associated fatty liver disease(MAFLD).However,the reliance on 16S rRNA sequencing data has led to inconsistent findings and limited species-level insights.To address this,we conducted a de novo MR analysis using species-level shotgun metagenomic data,combined it with a meta-analysis to consolidate the existing evidence,and explored metabolite-mediated pathways.Methods Bidirectional MR analyses were performed between 883 gut microbiota taxa(derived from shotgun metagenomic genome-wide association study)and MAFLD.Published MR studies(up to December 1,2024)were identified using PubMed,Embase,Web of Science,and the Cochrane Library for meta-analysis.Multivariable MR(MVMR)and mediation analyses were applied to assess the mediating effects of 1,400 blood metabolites.Results The de novo MR identified 25 MAFLD-associated microbial taxa.Integration with 7 published studies revealed 34 causal taxa,including 10 at the species level.Among the 1,400 metabolites,53 showed causal links with MAFLD.MVMR and mediation analyses identified deoxycholate as a mediator of the effect of Bifidobacterium on MAFLD risk(22.06%mediation proportion).Conclusion This study elucidated the connections between species-level gut microbiota and MAFLD,highlighting the interplay between microbiota,metabolites,and disease pathogenesis.These findings provide novel insights into the potential therapeutic targets for MAFLD.展开更多
Spinal cord injuries have overwhelming physical and occupational implications for patients.Moreover,the extensive and long-term medical care required for spinal cord injury significantly increases healthcare costs and...Spinal cord injuries have overwhelming physical and occupational implications for patients.Moreover,the extensive and long-term medical care required for spinal cord injury significantly increases healthcare costs and resources,adding a substantial burden to the healthcare system and patients'families.In this context,chondroitinase ABC,a bacterial enzyme isolated from Proteus vulgaris that is modified to facilitate expression and secretion in mammals,has emerged as a promising therapeutic agent.It works by degrading chondroitin sulfate proteoglycans,cleaving the glycosaminoglycanchains of chondroitin sulfate proteoglycans into soluble disaccharides or tetrasaccharides.Chondroitin sulfate proteoglycans are potent axon growth inhibitors and principal constituents of the extracellular matrix surrounding glial and neuronal cells attached to glycosaminoglycan chains.Chondroitinase ABC has been shown to play an effective role in promoting recovery from acute and chronic spinal cord injury by improving axonal regeneration and sprouting,enhancing the plasticity of perineuronal nets,inhibiting neuronal apoptosis,and modulating immune responses in various animal models.In this review,we introduce the classification and pathological mechanisms of spinal cord injury and discuss the pathophysiological role of chondroitin sulfate proteoglycans in spinal cord injury.We also highlight research advancements in spinal cord injury treatment strategies,with a focus on chondroitinase ABC,and illustrate how improvements in chondroitinase ABC stability,enzymatic activity,and delivery methods have enhanced injured spinal cord repair.Furthermore,we emphasize that combination treatment with chondroitinase ABC further enhances therapeutic efficacy.This review aimed to provide a comprehensive understanding of the current trends and future directions of chondroitinase ABC-based spinal cord injury therapies,with an emphasis on how modern technologies are accelerating the optimization of chondroitinase ABC development.展开更多
Background Frailty is common and significantly impacts prognosis in heart failure(HF). The Vulnerable Elders Survey-13(VES-13), widely used in oncogeriatrics and public health, remains unexplored as a frailty screenin...Background Frailty is common and significantly impacts prognosis in heart failure(HF). The Vulnerable Elders Survey-13(VES-13), widely used in oncogeriatrics and public health, remains unexplored as a frailty screening tool in HF outpatients. In this study, we prospectively evaluated VES-13 against a multimodal screening assessment in detecting frailty and predicting individual risk of adverse prognosis.Methods Frailty was assessed at the initial visit using both a multimodal approach, incorporating Barthel Index, Older American Resources and Services scale, Pfeiffer Test, abbreviated Geriatric Depression Scale, age > 85 years, lacking support systems,and VES-13. Patients scoring ≥ 3 on VES-13 or meeting at least one multimodal criterion were classified as frail. Endpoints included all-cause mortality, a composite of death or HF hospitalization, and recurrent HF hospitalizations.Results A total of 301 patients were evaluated. VES-13 identified 40.2% as frail and the multimodal assessment 33.2%. In Cox regression analyses, frailty identified by VES-13 showed greater prognostic significance than the multimodal assessment for allcause mortality(HR = 3.70 [2.15–6.33], P < 0.001 vs. 2.40 [1.46–4.0], P = 0.001) and the composite endpoint(HR = 3.13 [2.02–4.84], P< 0.001 vs. 1.96 [1.28–2.99], P = 0.002). Recurrent HF hospitalizations were four times more frequent in VES-13 frail patients while two times in those identified as frail by the multimodal assessment. Additionally, stratifying patients by VES-13 tertiles provided robust risk differentiation.Conclusions VES-13, a simple frailty tool, outperformed a comprehensive multimodal assessment and could be easily integrated into routine HF care, highlighting its clinical utility in identifying patients at risk for poor outcomes.展开更多
Neurodegenerative disorders represent an increasingly pertinent public health crisis.As a greater proportion of the population ages,neurodegenerative disorders and other diseases of aging place undue burdens on patien...Neurodegenerative disorders represent an increasingly pertinent public health crisis.As a greater proportion of the population ages,neurodegenerative disorders and other diseases of aging place undue burdens on patients,caregivers,and healthcare workers.Alzheimer’s disease(AD)and Parkinson’s disease represent the two most common neurodegenerative disorders in the population,affecting over 65 million people,worldwide.展开更多
Objective The associations of serum trace element levels with disease progression and survival duration were assessed in individuals diagnosed with sporadic amyotrophic lateral sclerosis(sALS)in China.Methods Clinical...Objective The associations of serum trace element levels with disease progression and survival duration were assessed in individuals diagnosed with sporadic amyotrophic lateral sclerosis(sALS)in China.Methods Clinical data,including diagnostic indicators,clinical characteristics,Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised(ALSFRS-R)scores,and serum concentrations of calcium(Ca),magnesium(Mg),iron(Fe),copper(Cu),and zinc(Zn),were collected for hospitalized patients with sALS between 2018 and 2021.Correlation analysis,random forest analysis,and the Gehan-Breslow-Wilcoxon test were used to evaluate the relations between serum trace element levels,disease progression,and survival duration.Results Lower serum Ca levels and higher Mg levels were observed in patients with ALSFRS-R scores<39.Serum Mg was significantly negatively correlated with ALSFRS-R,trunk,and respiratory scores.Serum Cu and Zn also showed significant negative correlations with the respiratory score,whereas Ca and Fe were not significantly correlated with the ALSFRS-R score.The serum levels of Ca,Mg,Cu,Zn,and Fe remained consistent regardless of the site of disease onset.ALSFRS-R analysis revealed that serum Ca and Mg had a substantial effect on the total ALSFRS-R score,with serum Mg significantly influencing the course of the disease.Notably,low serum Mg levels were associated with extended survival times in patients with sALS.Conclusion Serum levels of Ca and Mg play critical roles in the progression of sALS,and a reduced serum Mg level is related to an extended survival time.展开更多
Inflammation plays a key role in driving the secondary brain injury that follows ischemic stroke.Melatonin is an endogenous neuroendocrine hormone that regulates mitochondrial homeostasis.However,the role and mechanis...Inflammation plays a key role in driving the secondary brain injury that follows ischemic stroke.Melatonin is an endogenous neuroendocrine hormone that regulates mitochondrial homeostasis.However,the role and mechanisms by which melatonin regulates microglial pyroptosis and the inflammatory cascade through double-stranded DNA(dsDNA)-sensing cyclic GMP-AMP synthase(cGAS)signaling warrant further study.Using middle cerebral artery occlusion mice,we investigated the effects of melatonin on cGAS-mediated pyroptosis and neuroinflammation.Middle cerebral artery occlusion model mice exhibited significantly increased DNA damage and cytoplasmic dsDNA release,as reflected byγH2AX staining,as well as heightened activation of the cytosolic dsDNA-sensing cGAS-STING pathway,both of which were notably suppressed by melatonin treatment.Melatonin also mitigated NOD-like receptor family pyrin domain-containing protein 3(NLRP3)inflammasome activation and nuclear factor(NF)-κB/gasdermin D-mediated pyroptosis in microglia following ischemic stroke,while exhibiting the capacity to attenuate the immune response to ischemia in mice.This led to reduced infiltration of peripheral neutrophils and monocytes/macrophages in the ischemic brain.Specifically,melatonin administration resulted in reductions in the numbers of ionized calcium-binding adapter molecule 1-positive cells and production of interleukin-6 and tumor necrosis factor-αby microglia.Regarding neurological outcomes,melatonin significantly reduced cerebral infarct volume and ameliorated neurological deficits in mice.Notably,the neuroprotective effect of melatonin was correlated with the inhibition of cGAS activity.We also developed and tested melatonin co-loaded macrophage membrane-biomimetic reactive oxygen species-responsive nanoparticles(Mф-MLT@FNGs),which exhibited therapeutic properties in middle cerebral artery occlusion mice.Our findings suggest that melatonin acts on microglial pyroptosis to inhibit neuroinflammation and reshape the immune microenvironment through regulation of the cGAS-STING-NF-κB signaling pathway.By doing so,melatonin rescues damaged brain tissue and protects neurological function,highlighting its potential as a neuroprotective treatment for ischemic stroke.展开更多
Poor solubility often results in low efficacy of antitumor drugs.Nevertheless,limited research has been conducted on the potential decrease in drug efficacy following the self-assembly of hydrophobic pure drugs into n...Poor solubility often results in low efficacy of antitumor drugs.Nevertheless,limited research has been conducted on the potential decrease in drug efficacy following the self-assembly of hydrophobic pure drugs into nanodrugs,and solutions to this problem are even rarer.Loading water-insoluble antitumor drugs into nanocarriers offers a promising solution.However,intricate carrier preparation,limited drug loading capacity,and carrier-associated safety remain key challenges.In this study,based on the discovery that hydrophobic gambogic acid(GA) self-assembles into nanostructures with diminished antitumor efficacy in aqueous environments,we developed a carrier-free nanodrug system,designated as GA-S-S-AS nanoparticles(NPs),characterized by straightforward preparation,high drug loading,fluorescence imaging,tumor-targeting,and responsive drug release in reducing environments.Specifically,the hydrophobic GA was covalently linked to the hydrophilic aptamer through a disulfide bond and then self-assembled into the nanodrugs.About 92 % of drug was encapsulated in self-assembled NPs,demonstrating remarkable stability under physiological conditions and controlled release of GA in the high-glutathione environment characteristic of tumor sites.Furthermore,by utilizing the synergistic interaction between the enhanced permeability and retention(EPR) effect and ligand-receptor active targeting mechanisms,the nanodrugs significantly increased the accumulation of GA at tumor locations.Consequently,the nanodrugs exhibited optimal therapeutic efficacy against the tumor both in vitro and in vivo,significantly inhibiting tumor growth.Furthermore,the nanodrugs demonstrated enhanced biosafety compared to free GA,effectively reducing GA-induced hepatotoxicity.Taken together,these findings underscore the significant potential of this multifunctional carrier-free nanodrugs for the targeted delivery of GA,thereby laying a foundation for future endeavors aimed at developing novel formulations of hydrophobic antitumor drugs.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.
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.
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 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 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 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.
基金financially supported by National Natural Science Foundation(32302265).
文摘Driven by rapid global population growth and evolving consumer demands for high-quality nutrition and enhanced sensory enjoyment,the food industry is advancing towards healthier,more efficient,more sustainable,and more personalized targets.Notably,this transformation is being accelerated by the convergence of advanced biotechnology(BT)and information technology(IT)in food production systems.This review examines pivotal technologies shaping future food systems,highlighting two biotechnological frontiers and two artificial intelligence-driven domains.Specifically,evolutionary engineering enhances microbial resilience and production efficiency while synthetic biology expands the diversity of food sources and enables personalized food ingredient design,both of which advance sustainable food production.Meanwhile,artificial intelligence promotes food flavor innovation by integrating existing knowledge in molecular structure,flavoromics and consumer preferences.Furthermore,insights into gut microbiota,along with the development of omics techniques and wearable biosensors are unlocking attainable solutions for precision nutrition.Collectively,the trilateral convergence of BT,IT and food technology,embodying a harmonious balance,is reshaping the paradigm of future food manufacturing.
基金supported by the Beijing Natural Science Foundation(L242149)Research Project on High Quality Development of Hospital Pharmacy,National Institute of Hospital Administration,NHC,China(NIHAYS2332)+1 种基金National High Level Hospital Clinical Research Funding(BJ-2023-199)Capital Funds for Health Improvement and Research(CFH)(2024-1-4052).
文摘Objective To examine national trends in antibiotic consumption and antimicrobial resistance(AMR)among six WHO-priority bacterial pathogens in China from 2016 to 2022.Methods This ecological study analyzed national and provincial data from the China Antibacterial Resistance Surveillance System(CARSS)and the National Hospital Information Network.Beta regression models assessed temporal trends,and hierarchical models evaluated associations between antibiotic use and resistance.Results From 2016 to 2022,carbapenem resistance in Acinetobacter baumannii and Pseudomonas aeruginosa,and vancomycin resistance in Enterococcus faecium and E.faecalis significantly declined(β<0,P<0.010),while carbapenem-resistant Klebsiella pneumoniae increased(β=0.081,P<0.001).Nationwide antibiotic consumption rose across 10 major classes.Positive associations were found between carbapenem use and resistance in A.baumannii(z=2.719,P=0.007)and P.aeruginosa(z=3.241,P=0.001),and between vancomycin use and resistance in E.faecium(z=4.510,P=0.001)and E.faecalis(z=3.210,P=0.001).Conclusion Carbapenem-resistant K.pneumoniae increased significantly in China,while other resistant pathogens declined.Resistance patterns were linked to the use of multiple antibiotic classes,underscoring the need for strengthened antibiotic stewardship and surveillance.
文摘BACKGROUND Post-endoscopic retrograde cholangiopancreatography pancreatitis(PEP)is a prevalent and potentially serious complication in patients undergoing endoscopic retrograde cholangiopancreatography.AIM To comprehensively assess the efficacy of indomethacin therapy in reducing PEP risk.METHODS We searched PubMed,EMBASE,Scopus,and Cochrane Library databases to identify randomized controlled trials(RCTs)that compared rectal indomethacin with a control group to prevent PEP.Duplicates were removed,and studies were included based on the established inclusion criteria.We used the Cochrane Collaboration’s tool to assess the risk of bias in the RCTs.A random-effects model was applied to produce pooled risk ratios(RRs)with 95%confidence intervals(CIs).RESULTS We included a total of 30 RCTs involving 16977 patients.Compared to the control group,rectal indomethacin showed comparable rates of overall PEP(PEP;RR=0.85,95%CI:0.69-1.04,I2=79%)with no statistically significant difference of RR in mild(RR=0.92,95%CI:0.74-1.14),moderate(RR=0.78,95%CI:0.59-1.02),or severe PEP(RR=1.12,95%CI:0.75-1.67).There was also no difference in cases of adverse events(RR=0.97,95%CI:0.69-1.35),abdominal pain(RR=1.14,95%CI:0.80-1.62),bleeding(RR=1.07,95%CI:0.70-1.63),or mortality(RR=0.86,95%CI:0.56-1.33)between the two groups.Subgroup analyses were also performed.CONCLUSION Rectal indomethacin appears to be safe and may offer benefit in selected high-risk patients,though findings should be interpreted with caution due to high heterogeneity.
基金supported by grants from the National Natural Science Foundation of China(82270924)the CAMS Innovation Fund for Medical Sciences(CIFMS 2021-I2M-1-016)the National High Level Hospital Clinical Research Funding(2022-PUMCH-C-014,2025-PUMCH-C-041).
文摘Objective Previous Mendelian randomization(MR)studies have suggested an association between the gut microbiome and metabolic-associated fatty liver disease(MAFLD).However,the reliance on 16S rRNA sequencing data has led to inconsistent findings and limited species-level insights.To address this,we conducted a de novo MR analysis using species-level shotgun metagenomic data,combined it with a meta-analysis to consolidate the existing evidence,and explored metabolite-mediated pathways.Methods Bidirectional MR analyses were performed between 883 gut microbiota taxa(derived from shotgun metagenomic genome-wide association study)and MAFLD.Published MR studies(up to December 1,2024)were identified using PubMed,Embase,Web of Science,and the Cochrane Library for meta-analysis.Multivariable MR(MVMR)and mediation analyses were applied to assess the mediating effects of 1,400 blood metabolites.Results The de novo MR identified 25 MAFLD-associated microbial taxa.Integration with 7 published studies revealed 34 causal taxa,including 10 at the species level.Among the 1,400 metabolites,53 showed causal links with MAFLD.MVMR and mediation analyses identified deoxycholate as a mediator of the effect of Bifidobacterium on MAFLD risk(22.06%mediation proportion).Conclusion This study elucidated the connections between species-level gut microbiota and MAFLD,highlighting the interplay between microbiota,metabolites,and disease pathogenesis.These findings provide novel insights into the potential therapeutic targets for MAFLD.
基金supported by the National Natural Science Foundation of China,No.82002645China Postdoctoral Science Foundation,No.2022M722321Jiangsu Funding Program for Excellent Postdoctoral Talent,No.2022ZB552(all to YH)。
文摘Spinal cord injuries have overwhelming physical and occupational implications for patients.Moreover,the extensive and long-term medical care required for spinal cord injury significantly increases healthcare costs and resources,adding a substantial burden to the healthcare system and patients'families.In this context,chondroitinase ABC,a bacterial enzyme isolated from Proteus vulgaris that is modified to facilitate expression and secretion in mammals,has emerged as a promising therapeutic agent.It works by degrading chondroitin sulfate proteoglycans,cleaving the glycosaminoglycanchains of chondroitin sulfate proteoglycans into soluble disaccharides or tetrasaccharides.Chondroitin sulfate proteoglycans are potent axon growth inhibitors and principal constituents of the extracellular matrix surrounding glial and neuronal cells attached to glycosaminoglycan chains.Chondroitinase ABC has been shown to play an effective role in promoting recovery from acute and chronic spinal cord injury by improving axonal regeneration and sprouting,enhancing the plasticity of perineuronal nets,inhibiting neuronal apoptosis,and modulating immune responses in various animal models.In this review,we introduce the classification and pathological mechanisms of spinal cord injury and discuss the pathophysiological role of chondroitin sulfate proteoglycans in spinal cord injury.We also highlight research advancements in spinal cord injury treatment strategies,with a focus on chondroitinase ABC,and illustrate how improvements in chondroitinase ABC stability,enzymatic activity,and delivery methods have enhanced injured spinal cord repair.Furthermore,we emphasize that combination treatment with chondroitinase ABC further enhances therapeutic efficacy.This review aimed to provide a comprehensive understanding of the current trends and future directions of chondroitinase ABC-based spinal cord injury therapies,with an emphasis on how modern technologies are accelerating the optimization of chondroitinase ABC development.
文摘Background Frailty is common and significantly impacts prognosis in heart failure(HF). The Vulnerable Elders Survey-13(VES-13), widely used in oncogeriatrics and public health, remains unexplored as a frailty screening tool in HF outpatients. In this study, we prospectively evaluated VES-13 against a multimodal screening assessment in detecting frailty and predicting individual risk of adverse prognosis.Methods Frailty was assessed at the initial visit using both a multimodal approach, incorporating Barthel Index, Older American Resources and Services scale, Pfeiffer Test, abbreviated Geriatric Depression Scale, age > 85 years, lacking support systems,and VES-13. Patients scoring ≥ 3 on VES-13 or meeting at least one multimodal criterion were classified as frail. Endpoints included all-cause mortality, a composite of death or HF hospitalization, and recurrent HF hospitalizations.Results A total of 301 patients were evaluated. VES-13 identified 40.2% as frail and the multimodal assessment 33.2%. In Cox regression analyses, frailty identified by VES-13 showed greater prognostic significance than the multimodal assessment for allcause mortality(HR = 3.70 [2.15–6.33], P < 0.001 vs. 2.40 [1.46–4.0], P = 0.001) and the composite endpoint(HR = 3.13 [2.02–4.84], P< 0.001 vs. 1.96 [1.28–2.99], P = 0.002). Recurrent HF hospitalizations were four times more frequent in VES-13 frail patients while two times in those identified as frail by the multimodal assessment. Additionally, stratifying patients by VES-13 tertiles provided robust risk differentiation.Conclusions VES-13, a simple frailty tool, outperformed a comprehensive multimodal assessment and could be easily integrated into routine HF care, highlighting its clinical utility in identifying patients at risk for poor outcomes.
基金supported by the Canadian Institutes of Health Research(DFD-181599)the National Institutes of Health(T32AG058527)to RJB and R0190106435 to VM.
文摘Neurodegenerative disorders represent an increasingly pertinent public health crisis.As a greater proportion of the population ages,neurodegenerative disorders and other diseases of aging place undue burdens on patients,caregivers,and healthcare workers.Alzheimer’s disease(AD)and Parkinson’s disease represent the two most common neurodegenerative disorders in the population,affecting over 65 million people,worldwide.
文摘Objective The associations of serum trace element levels with disease progression and survival duration were assessed in individuals diagnosed with sporadic amyotrophic lateral sclerosis(sALS)in China.Methods Clinical data,including diagnostic indicators,clinical characteristics,Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised(ALSFRS-R)scores,and serum concentrations of calcium(Ca),magnesium(Mg),iron(Fe),copper(Cu),and zinc(Zn),were collected for hospitalized patients with sALS between 2018 and 2021.Correlation analysis,random forest analysis,and the Gehan-Breslow-Wilcoxon test were used to evaluate the relations between serum trace element levels,disease progression,and survival duration.Results Lower serum Ca levels and higher Mg levels were observed in patients with ALSFRS-R scores<39.Serum Mg was significantly negatively correlated with ALSFRS-R,trunk,and respiratory scores.Serum Cu and Zn also showed significant negative correlations with the respiratory score,whereas Ca and Fe were not significantly correlated with the ALSFRS-R score.The serum levels of Ca,Mg,Cu,Zn,and Fe remained consistent regardless of the site of disease onset.ALSFRS-R analysis revealed that serum Ca and Mg had a substantial effect on the total ALSFRS-R score,with serum Mg significantly influencing the course of the disease.Notably,low serum Mg levels were associated with extended survival times in patients with sALS.Conclusion Serum levels of Ca and Mg play critical roles in the progression of sALS,and a reduced serum Mg level is related to an extended survival time.
基金supported by the Natural Science Foundation of Heilongjiang Province,No.YQ2021H011(to QL)China Postdoctoral Science Foundation,Nos.2020M670925,2022T150172(to QL)+2 种基金Postdoctoral Foundation of Heilongjiang Province,Nos.LBH‐Z19027,LBH‐TZ2019(to QL)Institute Cultivation Fund,No.PYMS2023-1(to QL)Natural Science Foundation of Jiangsu Province,No.BK20241233(to YL).
文摘Inflammation plays a key role in driving the secondary brain injury that follows ischemic stroke.Melatonin is an endogenous neuroendocrine hormone that regulates mitochondrial homeostasis.However,the role and mechanisms by which melatonin regulates microglial pyroptosis and the inflammatory cascade through double-stranded DNA(dsDNA)-sensing cyclic GMP-AMP synthase(cGAS)signaling warrant further study.Using middle cerebral artery occlusion mice,we investigated the effects of melatonin on cGAS-mediated pyroptosis and neuroinflammation.Middle cerebral artery occlusion model mice exhibited significantly increased DNA damage and cytoplasmic dsDNA release,as reflected byγH2AX staining,as well as heightened activation of the cytosolic dsDNA-sensing cGAS-STING pathway,both of which were notably suppressed by melatonin treatment.Melatonin also mitigated NOD-like receptor family pyrin domain-containing protein 3(NLRP3)inflammasome activation and nuclear factor(NF)-κB/gasdermin D-mediated pyroptosis in microglia following ischemic stroke,while exhibiting the capacity to attenuate the immune response to ischemia in mice.This led to reduced infiltration of peripheral neutrophils and monocytes/macrophages in the ischemic brain.Specifically,melatonin administration resulted in reductions in the numbers of ionized calcium-binding adapter molecule 1-positive cells and production of interleukin-6 and tumor necrosis factor-αby microglia.Regarding neurological outcomes,melatonin significantly reduced cerebral infarct volume and ameliorated neurological deficits in mice.Notably,the neuroprotective effect of melatonin was correlated with the inhibition of cGAS activity.We also developed and tested melatonin co-loaded macrophage membrane-biomimetic reactive oxygen species-responsive nanoparticles(Mф-MLT@FNGs),which exhibited therapeutic properties in middle cerebral artery occlusion mice.Our findings suggest that melatonin acts on microglial pyroptosis to inhibit neuroinflammation and reshape the immune microenvironment through regulation of the cGAS-STING-NF-κB signaling pathway.By doing so,melatonin rescues damaged brain tissue and protects neurological function,highlighting its potential as a neuroprotective treatment for ischemic stroke.
基金the National Natural Science Foundation of China (Nos.21907076 and 31901908)the Natural Science Foundation of Tianjin (No.22JCQNJC01570)。
文摘Poor solubility often results in low efficacy of antitumor drugs.Nevertheless,limited research has been conducted on the potential decrease in drug efficacy following the self-assembly of hydrophobic pure drugs into nanodrugs,and solutions to this problem are even rarer.Loading water-insoluble antitumor drugs into nanocarriers offers a promising solution.However,intricate carrier preparation,limited drug loading capacity,and carrier-associated safety remain key challenges.In this study,based on the discovery that hydrophobic gambogic acid(GA) self-assembles into nanostructures with diminished antitumor efficacy in aqueous environments,we developed a carrier-free nanodrug system,designated as GA-S-S-AS nanoparticles(NPs),characterized by straightforward preparation,high drug loading,fluorescence imaging,tumor-targeting,and responsive drug release in reducing environments.Specifically,the hydrophobic GA was covalently linked to the hydrophilic aptamer through a disulfide bond and then self-assembled into the nanodrugs.About 92 % of drug was encapsulated in self-assembled NPs,demonstrating remarkable stability under physiological conditions and controlled release of GA in the high-glutathione environment characteristic of tumor sites.Furthermore,by utilizing the synergistic interaction between the enhanced permeability and retention(EPR) effect and ligand-receptor active targeting mechanisms,the nanodrugs significantly increased the accumulation of GA at tumor locations.Consequently,the nanodrugs exhibited optimal therapeutic efficacy against the tumor both in vitro and in vivo,significantly inhibiting tumor growth.Furthermore,the nanodrugs demonstrated enhanced biosafety compared to free GA,effectively reducing GA-induced hepatotoxicity.Taken together,these findings underscore the significant potential of this multifunctional carrier-free nanodrugs for the targeted delivery of GA,thereby laying a foundation for future endeavors aimed at developing novel formulations of hydrophobic antitumor drugs.
