Comparative proteomic analysis of plasma exosomes reveals the functional contribution of N-acetyl-alpha-glucosaminidase to Parkinson’s disease

Parkinson’s disease is the second most common progressive neurodegenerative disorder,and few reliable biomarkers are available to track disease progression.The proteins,DNA,mRNA,and lipids carried by exosomes reflect intracellular changes,and thus can serve as biomarkers for a variety of conditions.In this study,we investigated alterations in the protein content of plasma exosomes derived from patients with Parkinson’s disease and the potential therapeutic roles of these proteins in Parkinson’s disease.Using a tandem mass tag-based quantitative proteomics approach,we characterized the proteomes of plasma exosomes derived from individual patients,identified exosomal protein signatures specific to patients with Parkinson’s disease,and identified N-acetyl-alpha-glucosaminidase as a differentially expressed protein.N-acetyl-alpha-glucosaminidase expression levels in exosomes from the plasma of patients and healthy controls were validated by enzyme-linked immunosorbent assay and western blot.The results demonstrated that the exosomal N-acetyl-alpha-glucosaminidase concentration was not only lower in Parkinson’s disease,but also decreased with increasing Hoehn-Yahr stage,suggesting that N-acetyl-alpha-glucosaminidase could be used to rapidly evaluate Parkinson’s disease severity.Furthermore,western blot and immunohistochemistry analysis showed that N-acetyl-alpha-glucosaminidase levels were markedly reduced both in cells treated with 1-methyl-4-phenylpyridinium and cells overexpressingα-synuclein compared with control cells.Additionally,N-acetyl-alpha-glucosaminidase overexpression significantly increased cell viability and inhibitedα-synuclein expression in 1-methyl-4-phenylpyridinium-treated cells.Taken together,our findings demonstrate for the first time that exosomal N-acetyl-alpha-glucosaminidase may serve as a biomarker for Parkinson’s disease diagnosis,and that N-acetyl-alpha-glucosaminidase may reduceα-synuclein expression and 1-methyl-4-phenylpyridinium-induced neurotoxicity,thus providing a new therapeutic target for Parkinson’s disease.

Quality of life, physical performance and nutritional status in older patients hospitalized in a cardiology department

Objectives Quality of life(QoL) is a priority outcome in older adults suffering from cardiovascular diseases. Frailty and poor nutritional status may affect the QoL through mobility disorders and exhaustion. The objective of this study was to determine if physical frailty and nutritional status were associated with QoL, in older cardiology patients. Methods Cross sectional, observational study conducted in a cardiology department from a university hospital. Participants(n = 100) were aged 70 and older. Collected data included age, sex, cardiac diseases, New York Heart Association(NYHA) classification, comorbidities(Charlson Index) and disability. A Short Physical Performance Battery(SPPB), including walking speed assessment was performed;handgrip strength were measured as well as Fried’s frailty phenotype. Nutritional status was assessed using the Mini Nutritional Assessment(MNA) and Body Mass Index(BMI), inflammation by C-reactive protein(CRP). QoL was assessed using the EORTC–QLQ questionnaire. Univariate and multivariate analyses were performed to study the associations between all recorded parameters and QoL. Results In participants(mean age: 79.3 ± 6.7 years;male: 59%), Charlson index, arrhythmia, heart failure, NYHA class III-IV, MNA, disability, walking speed, SPPB score, frailty and CRP were significantly associated with QoL in univariate analysis. Multivariate analysis showed that NYHA class III-IV(P < 0.001), lower MNA score(P = 0.03), frailty(P < 0.0001), and higher CRP(P < 0.001) were independently associated with decreased QoL. Conclusions Frailty, nutritional status and inflammation were independently associated with poor QoL. Further studies are needed to assess the efficacy of nutritional and physical interventions on QoL in this population.

Efficacy of hepatic arterial infusion chemotherapy and its combination strategies for advanced hepatocellular carcinoma:A network meta-analysis

BACKGROUND With the rapid progress of systematic therapy for hepatocellular carcinoma(HCC),therapeutic strategies combining hepatic arterial infusion chemotherapy(HAIC)with systematic therapy arised increasing concentrations.However,there have been no systematic review comparing HAIC and its combination strategies in the first-line treatment for advanced HCC.AIM To investigate the efficacy and safety of HAIC and its combination therapies for advanced HCC.METHODS A network meta-analysis was performed by including 9 randomized controlled trails and 35 cohort studies to carry out our study.The outcomes of interest comprised overall survival(OS),progression-free survival(PFS),tumor response and adverse events.Hazard ratios(HR)and odds ratios(OR)with a 95% confidence interval(CI)were calculated and agents were ranked based on their ranking probability.RESULTS HAIC outperformed Sorafenib(HR=0.55,95%CI:0.42-0.72;HR=0.51,95%CI:0.33-0.78;OR=2.86,95%CI:1.37-5.98;OR=5.45,95%CI:3.57-8.30;OR=7.15,95%CI:4.06-12.58;OR=2.89,95%CI:1.99-4.19;OR=0.48,95%CI:0.25-0.92,respectively)and transarterial chemoembolization(TACE)(HR=0.50,95%CI:0.33-0.75;HR=0.62,95%CI:0.39-0.98;OR=3.08,95%CI:1.36-6.98;OR=2.07,95%CI:1.54-2.80;OR=3.16,95%CI:1.71-5.85;OR=2.67,95%CI:1.59-4.50;OR=0.16,95%CI:0.05-0.54,respectively)in terms of efficacy and safety.HAIC+lenvatinib+ablation,HAIC+ablation,HAIC+anti-programmed cell death 1(PD-1),and HAIC+radiotherapy had the higher likelihood of providing better OS and PFS outcomes compared to HAIC alone.HAIC+TACE+S-1,HAIC+lenvatinib,HAIC+PD-1,HAIC+TACE,and HAIC+sorafenib had the higher likelihood of providing better partial response and objective response rate outcomes compared to HAIC.HAIC+PD-1,HAIC+TACE+S-1 and HAIC+TACE had the higher likelihood of providing better complete response and disease control rate outcomes compared to HAIC alone.CONCLUSION HAIC proved more effective and safer than sorafenib and TACE.Furthermore,combined with other interventions,HAIC showed improved efficacy over HAIC monotherapy according to the treatment ranking analysis.

Impact of frailty on outcomes of elderly patients undergoing percutaneous coronary intervention: A systematic review and metaanalysis

BACKGROUND Frailty is a common condition in elderly patients who receive percutaneous coronary intervention(PCI).However,how frailty affects clinical outcomes in this group is unclear.AIM To assess the link between frailty and the outcomes,such as in-hospital complic-ations,post-procedural complications,and mortality,in elderly patients post-PCI.METHODS The PubMed/MEDLINE,EMBASE,Cochrane Library,and Web of Science databases were screened for publications up to August 2023.The primary outcomes assessed were in-hospital and all-cause mortality,major adverse cardiovascular events(MACEs),and major bleeding.The Newcastle-Ottawa Scale was used for quality assessment.RESULTS Twenty-one studies with 739693 elderly patients undergoing PCI were included.Frailty was consistently associated with adverse outcomes.Frail patients had significantly higher risks of in-hospital mortality[risk ratio:3.45,95%confidence interval(95%CI):1.90-6.25],all-cause mortality[hazard ratio(HR):2.08,95%CI:1.78-2.43],MACEs(HR:2.92,95%CI:1.85-4.60),and major bleeding(HR:4.60,95%CI:2.89-7.32)compared to non-frail patients.CONCLUSION Frailty is a pivotal determinant in the prediction of risk of mortality,development of MACEs,and major bleeding in elderly individuals undergoing percutaneous coronary intervention.

Effect of infarct location and volume on cognitive dysfunction in elderly patients with acute insular cerebral infarction

BACKGROUND The aging of the population has become increasingly obvious in recent years,and the incidence of cerebral infarction has shown an increasing trend annually,with high death and disability rates.AIM To analyze the effects of infarct location and volume on cognitive dysfunction in elderly patients with acute insular cerebral infarction.METHODS Between January 2020 and December 2023,we treated 98 cases of elderly acute insula,patients with cerebral infarction in the cerebral infarction acute phase(3-4 weeks)and for the course of 6 months in Montreal Cognitive Assessment Scale(MoCA)for screening of cognition.Notably,58 and 40 patients were placed in the cognitive impairment group and without-cognitive impairment group,respec-tively.In patients with cerebral infarction,magnetic resonance imaging was used to screen and clearly analyze the MoCA scores of two groups of patients with different infarctions,the relationship between the parts of the infarction volume,and analysis of acute insula cognitive disorder in elderly patients with cerebral RESULTS The number of patients with cognitive impairment in the basal ganglia and thalamus was significantly higher than that without cognitive impairment(P<0.05).The total infarct volume in the cognitive impairment group was higher than that in the non-cognitive impairment group,and the difference was statistically significant(P<0.05).The infarct volumes at different sites in the cognitive impairment group was higher than in the non-cognitive impairment group(P<0.05).In the cognitive impairment group,the infarct volumes in the basal ganglia,thalamus,and mixed lesions were negatively correlated with the total MoCA score,with correlation coefficients of-0.67,-0.73,and-0.77,respectively.CONCLUSION In elderly patients with acute insular infarction,infarction in the basal ganglia,thalamus,and mixed lesions were more likely to lead to cognitive dysfunction than in other areas,and patients with large infarct volumes were more likely to develop cognitive dysfunction.The infarct volume in the basal ganglia,thalamus,and mixed lesions was significantly negatively correlated with the MoCA score.

Assessment of Falls among the Elderly in the Emergency Department of the Idrissa Pouye General Hospital in Dakar, Senegal: A Cohort of 100 Cases

Background: Falls in the elderly are a global public health problem with serious medical and socio-economic consequences, especially in low and middle-income countries. The aim of this study was to describe the characteristics of falls among the elderly in trauma units in Senegal. Materials and Methods: This was a descriptive, prospective study from April 20, 2022 to October 30, 2022 among people aged at least 60 and admitted to the surgical emergency department of Idrissa Pouye Hospital in Dakar following a fall. Socio-demographic, clinical, therapeutic and evolutionary characteristics were collected and analyzed using Sphinx Plus 2 and Excel 2019 for Windows software. Results: Out of 730 elderly people seen during this period, 100 met the criteria, representing a prevalence of 13.69%. The average consultation time was 3.25 +/? 4 days. The average age was 73 +/? 8.43 years, with women predominating (74%). Medical expenses were mainly covered by the family (73%). Most falls occurred during the day (68%), at home (82%), especially in the bedroom (30%), with stumbling (32%) as the main mechanism. The majority of patients (86%) spent less than 30 minutes on the floor. Predisposing factors were dominated by visual disorders (56%) and precipitating factors were mainly environmental (62%). Geriatric syndromes were dominated by frailty (22%). Complications were dominated by fractures (86%), and almost half (47%) had lost their autonomy for post-fall Activities Daily Living (ADL). Prescription medication was almost systematic (98%), dominated by analgesics (98%). Surgery was indicated in 58% of patients. The average waiting time for surgery was 25.36 +/? 19 days. A death rate of 1% was recorded in the emergency department. Conclusion: Falls in the elderly are a frequent occurrence in traumatological emergencies, with etiological factors that are often multiple and interrelated, leading to significant morbidity. Raising awareness among people at risk and setting up an orthogeriatric service would help prevent falls and optimize care in the short and long term.

Association between Gene Polymorphisms and SNP-SNP Interactions of the Matrix Metalloproteinase 2 Signaling Pathway and the Risk of Vascular Senescence

Objective This study aimed to explore the association of single nucleotide polymorphisms(SNP)in the matrix metalloproteinase 2(MMP-2)signaling pathway and the risk of vascular senescence(VS).Methods In this cross-sectional study,between May and November 2022,peripheral venous blood of151 VS patients(case group)and 233 volunteers(control group)were collected.Fourteen SNPs were identified in five genes encoding the components of the MMP-2 signaling pathway,assessed through carotid-femoral pulse wave velocity(cf PWV),and analyzed using multivariate logistic regression.The multigene influence on the risk of VS was assessed using multifactor dimensionality reduction(MDR)and generalized multifactor dimensionality regression(GMDR)modeling.Results Within the multivariate logistic regression models,four SNPs were screened to have significant associations with VS:chemokine(C-C motif)ligand 2(CCL2)rs4586,MMP2 rs14070,MMP2rs7201,and MMP2 rs1053605.Carriers of the T/C genotype of MMP2 rs14070 had a 2.17-fold increased risk of developing VS compared with those of the C/C genotype,and those of the T/T genotype had a19.375-fold increased risk.CCL2 rs4586 and MMP-2 rs14070 exhibited the most significant interactions.Conclusion CCL2 rs4586,MMP-2 rs14070,MMP-2 rs7201,and MMP-2 rs1053605 polymorphisms were significantly associated with the risk of VS.

Metformin administration in prevention of colorectal polyps in type 2 diabetes mellitus patients

BACKGROUND Colorectal polyps are frequently observed in patients with type 2 diabetes mellitus(DM),posing a significant risk for colorectal cancer.Metformin,a widely prescribed biguanidine drug for type 2 DM,has been suggested to have potential chemoprophylactic effects against various cancers.AIM To explore the correlation between colorectal polyps and metformin use in type 2 DM patients.METHODS Type 2 DM patients were categorized into polyp and non-polyp groups.Following this,all patients were categorized into the type 2 DM-metformin,type 2 DM-non-metformin,and non-type 2 DM groups.Based on the baseline colonoscopy results,we performed pairwise comparisons of the incidence of colorectal polyps among the three groups.Additionally,we analyzed the relationship between colorectal polyps and the duration of metformin use and between the size and number of polyps and metformin use.Simultaneously,we focused on the specific pathological types of polyps and analyzed their relationship with metformin use.Finally,we compared the incidence of polyps between metformin and non-metformin groups according to the interval colonoscopy results.RESULTS The rate of metformin use in patients with colorectal polyps was 0.502 times that of patients without colorectal polyps[odds ratio(OR)=0.502,95%confidence interval(CI):0.365-0.689;P<0.001].The incidence of colorectal polyps did not differ significantly between the type 2 DM-metformin and non-type 2 DM groups(P>0.05).Furthermore,the correlations between the duration of metformin use and the incidence of colorectal polyps and between the size and number of polyps and metformin use were not statistically significant(P>0.05).Metformin use did not affect the incidence of colorectal polyps during interval colonoscopy(P>0.05).CONCLUSION Metformin use and colorectal polyp incidence in type 2 DM patients showed a negative correlation,independent of the hypoglycemic effect of metformin.

Optimal timing of invasive intervention for high-risk non-ST-segment-elevation myocardial infarction patients

OBJECTIVE To compare the immediate,early,and delayed percutaneous coronary intervention(PCI)strategies in non-ST-segment-elevation myocardial infarction(NSTEMI)patients with high-risk.METHODS Medical records of patients treated at the Daping Hospital,Third Military Medical University,Chongqing,China between 2011 and 2021 were retrospectively reviewed.Only patients with complete available information were included.All patients assigned into three groups based on the timing of PCI including immediate(<2 h),early(2–24 h)and delayed(≥24 h)intervention.Multivariable Cox hazards regression and simpler nonlinear models were performed.RESULTS A total of 657 patients were included in the study.The median follow-up length was 3.29(interquartile range:1.45–4.85)years.Early PCI strategy improved the major adverse cardiac event(MACE)outcome compared to the immediate or delayed PCI strategy.Early PCI,diabetes mellitus,and left main or/and left anterior descending or/and left circumflex stenosis or/and right coronary artery≥99%were predictors for MACE outcome.The optimal timing range for PCI to reduce MACE risk is 3–14 h post-admission.For high-risk NSTEMI patients,early PCI reduced primary clinical outcomes compared to immediate or delayed PCI,and the optimal timing range was 3–14 h post-admission.Delayed PCI was superior for NSTEMI with chronic kidney injury.CONCLUSIONS Delayed invasive strategy was helpful to reduce the incidence of MACE for high-risk NSTEMI with chronic kidney injury.An immediate PCI strategy might increase the rate of MACE.

CircPMS1 promotes proliferation of pulmonary artery smooth muscle cells,pulmonary microvascular endothelial cells,and pericytes under hypoxia

Background:Circular RNAs(circRNAs)have been recognized as significant regulators of pulmonary hypertension(PH);however,the differential expression and function of circRNAs in different vascular cells under hypoxia remain unknown.Here,we identified co-differentially expressed circRNAs and determined their putative roles in the proliferation of pulmonary artery smooth muscle cells(PASMCs),pulmonary microvascular endothelial cells(PMECs),and pericytes(PCs)under hypoxia.Methods:Whole transcriptome sequencing was performed to analyze the differential expression of circRNAs in three different vascular cell types.Bioinformatic analysis was used to predict their putative biological function.Quantitative real-time polymerase chain reaction,Cell Counting Kit-8,and EdU Cell Proliferation assays were carried out to determine the role of circular postmeiotic segregation 1(circPMS1)as well as its potential sponge mechanism in PASMCs,PMECs,and PCs.Results:PASMCs,PMECs,and PCs exhibited 16,99,and 31 differentially expressed circRNAs under hypoxia,respectively.CircPMS1 was upregulated in PASMCs,PMECs,and PCs under hypoxia and enhanced the proliferation of vascular cells.CircPMS1may upregulate DEP domain containing 1(DEPDC1)and RNA polymerase II subunit D expression by targeting microRNA-432-5p(miR-432-5p)in PASMCs,upregulate MAX interactor 1(MXI1)expression by targeting miR-433-3p in PMECs,and upregulate zinc finger AN1-type containing 5(ZFAND5)expression by targeting miR-3613-5p in PCs.Conclusions:Our results suggest that circPMS1 promotes cell proliferation through the miR-432-5p/DEPDC1 or miR-432-5p/POL2D axis in PASMCs,through the miR-433-3p/MXI1 axis in PMECs,and through the miR-3613-5p/ZFAND5 axis in PCs,which provides putative targets for the early diagnosis and treatment of PH.

Crosstalk among Oxidative Stress,Autophagy,and Apoptosis in the Protective Effects of Ginsenoside Rb1 on Brain Microvascular Endothelial Cells:A Mixed Computational and Experimental Study

Objective Brain microvascular endothelial cells (BMECs) were found to shift from their usually inactive state to an active state in ischemic stroke (IS) and cause neuronal damage. Ginsenoside Rb1 (GRb1),a component derived from medicinal plants,is known for its pharmacological benefits in IS,but its protective effects on BMECs have yet to be explored. This study aimed to investigate the potential protective effects of GRb1 on BMECs. Methods An in vitro oxygen-glucose deprivation/reperfusion (OGD/R) model was established to mimic ischemia-reperfusion (I/R) injury. Bulk RNA-sequencing data were analyzed by using the Human Autophagy Database and various bioinformatic tools,including gene set enrichment analysis (GSEA),Gene Ontology (GO) classification and enrichment analysis,Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis,protein-protein interaction network analysis,and molecular docking. Experimental validation was also performed to ensure the reliability of our findings. Results Rb1 had a protective effect on BMECs subjected to OGD/R injury. Specifically,GRb1 was found to modulate the interplay between oxidative stress,apoptosis,and autophagy in BMECs. Key targets such as sequestosome 1 (SQSTM1/p62),autophagy related 5 (ATG5),and hypoxia-inducible factor 1-alpha (HIF-1α) were identified,highlighting their potential roles in mediating the protective effects of GRb1 against IS-induced damage. Conclusion GRbl protects BMECs against OGD/R injury by influencing oxidative stress,apoptosis,and autophagy. The identification of SQSTM1/p62,ATG5,and HIF-1α as promising targets further supports the potential of GRb1 as a therapeutic agent for IS,providing a foundation for future research into its mechanisms and applications in IS treatment.

Effect of cytochrome P4502C19(CYP2C19)gene polymorphism and clopidogrel reactivity on long term prognosis of patients with coronary heart disease after PCI

Objective To investigate the impact of CYP2C19 gene polymorphism on clopidogrel reactivity and its association with longterm clinical outcome in patients with coronary heart disease(CHD)undergoing percutaneous coronary intervention(PCI).Methods In total,675 patients were enrolled.Based on the platelet inhibition rate,patients were categorized into two groups:clopidogrel low responsiveness(CLR)and normal clopidogrel responsiveness(NCR).The CLR group was divided into ticagrelor and clopidogrel group based on the antiplatelet drugs used in the follow-up treatment.Patients were classified into three groups(normal metabolizer,intermediate metabolizer,and poor metabolizer)based on the CYP2C19 genotype.We aimed to evaluate the impact of CYP2C19 gene polymorphism on clopidogrel reactivity.The cumulative rates of 12-month all-cause deaths,major adverse cardiovascular events(MACCEs),and bleeding events were calculated.Results CLR was observed in 44.4%of the overall population.Significant differences were observed in the platelet inhibition rate of clopidogrel among the three metabolic genotypes(P<0.05).At the 12-month follow-up,13 patients(1.9%)died and 96 patients(14.2%)experienced MACCEs.Patients with CLR(9.6%vs.11.7%vs.22.1%,P<0.05)or poor metabolizer(10.7%vs.16.4%vs.22.6%,P=0.026)experienced a higher rate of MACCEs.A MACCEs risk score between zero and two was calculated.The highest incidence of MACCEs significantly increased with the 2-positive results,and the area under the curve(AUC)was 0.712(95%CI:0.650-0.774,P<0.05).There was no significant difference between the group with a score of one and the occurrence of MACCEs(P>0.05).Conclusions Low response to clopidogrel in CHD patients is correlated with CYP2C19 gene polymorphism.CYP2C19 genotyping combined with platelet reactivity is an independent predictor of 12-months MACCEs in patients with clopidogrel treatment after PCI,which is better than either test alone.

Effects of atrial septal defects on the cardiac conduction system

The case report presented in this edition by Mu et al.The report presents a case of atrial septal defect(ASD)associated with electrocardiographic changes,noting that the crochetage sign resolved after Selective His Bundle Pacing(S-HBP)without requiring surgical closure.The mechanisms behind the appearance and resolution of the crochetage sign remain unclear.The authors observed the dis-appearance of the crochetage sign post-S-HBP,suggesting a possible correlation between these specific R waves and the cardiac conduction system.This editorial aims to explore various types of ASD and their relationship with the cardiac con-duction system,highlighting the diagnostic significance of the crochetage sign in ASD.

Exploration of cardiac rehabilitation nursing for elderly patients with myocardial infarction based on individualized cardiac rehabilitation

BACKGROUND Myocardial infarction is a high-risk condition prevalent among the elderly population,often leading to adverse clinical manifestations such as reduced cardiopulmonary function,anxiety,and depression post-surgery.Consequently,cardiac rehabilitation holds immense importance in mitigating these complications.AIM To evaluate the effect of individualized cardiac rehabilitation on blood pressure variability(BPV)and baroreflex sensitivity(BRS)in elderly patients with myocardial infarction.METHODS A cohort of 74 elderly patients diagnosed with myocardial infarction and admitted to our hospital between January 2021 and January 2022 were subjected to random selection.Subsequently,all patients were divided into two groups,namely the research group(n=37)and the control group(n=37),utilizing the number table method.The control group received conventional drug treatment and nursing guidance intervention,while the study group underwent individualized cardiac rehabilitation in addition to the interventions received by the control group.All patients were continuously intervened for 12 wk,and the BPV of these two groups in the 1st wk(T0),the 4th wk(T1)and the 12th wk(T2)were compared,BRS,changes in cardiopulmonary function measures,and adverse cardiovascular events.RESULTS Of 24 h diastolic BPV,24 h systolic BPV,carbon dioxide ventilation equivalent slope of the research group were lower than those of the control group at T1 and T2,BRS,peak heart rate and systolic blood pressure product,1 min heart rate recovery were higher than those of the control group,and the incidence of adverse events in the research group was lower than that of the control group,the difference was statistically significant(P<0.05).CONCLUSION In this study,we found that after individualized cardiac rehabilitation in elderly patients with myocardial infarction,BPV and BRS can be effectively improved,cardiac function is significantly enhanced,and a better prognosis is obtained.

Advances in the management of arteriosclerosis of the lower extremity:Integrating Western and Chinese medicine approaches

This editorial provides a commentary on the recent article.The paper reviews current literature and explores innovative treatment strategies for lower extremity arteriosclerosis obliterans(LEASO)through an integrative approach.It highlights the effectiveness of combination therapies that merge traditional Chinese medicine(TCM)with Western medical practices,suggesting that such integrative methods may improve patient compliance and outcomes through personalized care.This paper stresses the importance of rigorous clinical trials to evaluate the efficacy and safety of TCM interventions within LEASO treatment protocols,advocating for evidence-based validation of these combined therapies.Our recommendations emphasize accurate diagnosis,appropriate pharmacological in-terventions,the use of advanced surgical and endovascular techniques,and the inclusion of TCM to address underlying dysfunctions.Additionally,continuous monitoring,patient education,and lifestyle modifications are essential to slow disease progression and achieve optimal patient outcomes.The paper concludes by calling for further research to develop standardized treatment protocols that effectively integrate both Western and Chinese medical approaches in managing LEASO.

Injectable Nanorobot-Hydrogel Superstructure for Hemostasis and Anticancer Therapy of Spinal Metastasis

Surgery remains the standard treatment for spinal metastasis.However,uncontrolled intraoperative bleeding poses a significant challenge for adequate surgical resection and compromises surgical outcomes.In this study,we develop a thrombin(Thr)-loaded nanorobothydrogel hybrid superstructure by incorporating nanorobots into regenerated silk fibroin nanofibril hydrogels.This superstructure with superior thixotropic properties is injected percutaneously and dispersed into the spinal metastasis of hepatocellular carcinoma(HCC)with easy bleeding characteristics,before spinal surgery in a mouse model.Under near-infrared irradiation,the self-motile nanorobots penetrate into the deep spinal tumor,releasing Thr in a controlled manner.Thr-induced thrombosis effectively blocks the tumor vasculature and reduces bleeding,inhibiting tumor growth and postoperative recurrence with Au nanorod-mediated photothermal therapy.Our minimally invasive treatment platform provides a novel preoperative therapeutic strategy for HCC spinal metastasis effectively controlling intraoperative bleeding and tumor growth,with potentially reduced surgical complications and enhanced operative outcomes.

Mapping the evolution of liver aging research:A bibliometric analysis

BACKGROUND With the increasing of the global aging population,healthy aging and prevention of age-related diseases have become increasingly important.The liver,a vital organ involved in metabolism,detoxification,digestion,and immunity,holds a pivotal role in the aging process of organisms.Although extensive research on liver aging has been carried out,no bibliometric analysis has been conducted to evaluate the scientific progress in this area.AIM To analyze basic knowledge,development trends,and current research frontiers in the field via bibliometric methods.METHODS We conducted bibliometric analyses via a range of analytical tools including Python,the bibliometrix package in R,CiteSpace,and VOSviewer.We retrieved publication data on liver aging research from the Web of Science Core Collection Database.A scientific knowledge map was constructed to display the contributions from different authors,journals,countries,institutions,as well as patterns of co-occurrence keywords and co-cited references.Additionally,gene regulation pathways associated with liver aging were analyzed via the STRING database.RESULTS We identified 4288 articles on liver aging,authored by 24034 contributors from 4092 institutions across 85 countries.Notably,the years 1991 and 2020 presented significant bursts in publication output.The United States led in terms of publications(n=1008,25.1%),citations(n=55205),and international collaborations(multiple country publications=214).Keywords such as“lipid metabolism”,“fatty liver disease”,“inflammation”,“liver fibrosis”and“target”were prominent,highlighting the current research hotspots.Notably,the top 64 genes,each of which appeared in at least 8 articles,were involved in pathways essential for cell survival and aging,including the phosphatidylinositol 3-kinase/protein kinase B,Forkhead box O and p53 signaling pathways.CONCLUSION This study highlights key areas of liver aging and offers a comprehensive overview of research trends,as well as insights into potential value for collaborative pursuits and clinical implementations.

Impact of next-generation sequencing on antimicrobial treatment in immunocompromised adults with suspected infections

BACKGROUND:Prompt pathogen identification can have a substantial impact on the optimization of antimicrobial treatment.The objective of the study was to assess the diagnostic value of next-generation sequencing(NGS)for identifying pathogen and its clinical impact on antimicrobial intervention in immunocompromised patients with suspected infections.METHODS:This was a retrospective study.Between January and August 2020,47 adult immunocompromised patients underwent NGS testing under the following clinical conditions:1)prolonged fever and negative conventional cultures;2)new-onset fever despite empiric antimicrobial treatment;and 3)afebrile with suspected infections on imaging.Clinical data,including conventional microbial test results and antimicrobial treatment before and after NGS,were collected.Data were analyzed according to documented changes in antimicrobial treatment(escalated,no change,or deescalated)after the NGS results.RESULTS:The median time from hospitalization to NGS sampling was 19 d.Clinically relevant pathogens were detected via NGS in 61.7% of patients(29/47),more than half of whom suffered from fungemia(n=17),resulting in an antimicrobial escalation in 53.2% of patients(25/47)and antimicrobial de-escalation in 0.2% of patients(1/47).Antimicrobial changes were mostly due to the identification of fastidious organisms such as Legionella,Pneumocystis jirovecii,and Candida.In the remaining three cases,NGS detected clinically relevant pathogens also detected by conventional cultures a few days later.The antimicrobial treatment was subsequently adjusted according to the susceptibility test results.Overall,NGS changed antimicrobial management in 55.3%(26/47)of patients,and conventional culture detected clinically relevant pathogens in 14.9% of the patients(7/47).CONCLUSION:With its rapid identification and high sensitivity,NGS could be a promising tool for identifying relevant pathogens and enabling rapid appropriate treatment in immunocompromised patients with suspected infections.

Geriatric nursing competence of clinical nursing staff at different hospital levels in Chongqing,China:A cross-sectional study

Objectives:This study aimed to survey the geriatric nursing competencies of clinical nursing staff in Chongqing City,China,and provide suggestions to enhance these competencies.Methods:This study was conducted in 204 hospitals in Southwest China from December 24,2022 to January 7,2023.The“Geriatric Nursing Competence of Clinical Nurse Investigation Tool”was used to explore factors that influence geriatric nurses’competencies via stratified sampling.The survey was conducted by distributing and collecting questionnaires through the online platform Wenjuanxing.Results:A total of 10,692 nurses answered the questionnaires.Of these questionnaires,9,442 were valid.The total geriatric nursing competence score of the clinical nursing staff was 2.29±0.81,the secondary hospital score was 2.23±0.78,and the tertiary hospital’s overall mean score was 2.33±0.83.The factors that influenced secondary hospitals included the department of medicine,age of nurses and total length of career(P<0.05).The factors that influenced tertiary hospitals included the department of medicine,age of nurses,nurses’professional title,and geriatric practical advanced nurses’certification(P<0.05).Conclusions:Geriatric nursing competence among clinical nursing staff is imbalanced at a lower-middle level and is influenced by various factors.Thefindings highlight the need for further clinical training in geriatric nursing.The training of geriatric nurses should focus on necessary clinical skills and on preparing them to adequately manage comprehensive geriatric syndromes.

Anti-inflammatory and DNA Repair Effects of Astragaloside IV on PC12 Cells Damaged by Lipopolysaccharide

Objective This study aimed to establish a neural cell injury model in vitro by stimulating PC12 cells with lipopolysaccharide(LPS)and to examine the effects of astragaloside IV on key targets using high-throughput sequence technology and bioinformatics analyses.Methods PC12 cells in the logarithmic growth phase were treated with LPS at final concentrations of 0.25,0.5,0.75,1,and 1.25 mg/mL for 24 h.Cell morphology was evaluated,and cell survival rates were calculated.A neurocyte inflammatory model was established with LPS treatment,which reached a 50%cell survival rate.PC12 cells were treated with 0.01,0.1,1,10,or 100µmol/L astragaloside IV for 24 h.The concentration of astragaloside IV that did not affect the cell survival rate was selected as the treatment group for subsequent experiments.NOS activity was detected by colorimetry;the expression levels of ERCC2,XRCC4,XRCC2,TNF-α,IL-1β,TLR4,NOS and COX-2 mRNA and protein were detected by RT-qPCR and Western blotting.The differentially expressed genes(DEGs)between the groups were screened using a second-generation sequence(fold change>2,P<0.05)with the following KEGG enrichment analysis,RT-qPCR and Western blotting were used to detect the mRNA and protein expression of DEGs related to the IL-17 pathway in different groups of PC12 cells.Results The viability of PC12 cells was not altered by treatment with 0.01,0.1,or 1µmol/L astragaloside IV for 24 h(P>0.05).However,after treatment with 0.5,0.75,1,or 1.25 mg/mL LPS for 24 h,the viability steadily decreased(P<0.01).The mRNA and protein expression levels of ERCC2,XRCC4,XRCC2,TNF-α,IL-1β,TLR4,NOS,and COX-2 were significantly increased after PC12 cells were treated with 1 mg/mL LPS for 24 h(P<0.01);however,these changes were reversed when PC12 cells were pretreated with 0.01,0.1,or 1µmol/L astragaloside IV in PC12 cells and then treated with 1 mg/mL LPS for 24 h(P<0.05).Second-generation sequencing revealed that 1026 genes were upregulated,while 1287 genes were downregulated.The DEGs were associated with autophagy,TNF-α,interleukin-17,MAPK,P53,Toll-like receptor,and NOD-like receptor signaling pathways.Furthermore,PC12 cells treated with a 1 mg/mL LPS for 24 h exhibited increased mRNA and protein expression of CCL2,CCL11,CCL7,MMP3,and MMP10,which are associated with the IL-17 pathway.RT-qPCR and Western blotting analyses confirmed that the DEGs listed above corresponded to the sequence assay results.Conclusion LPS can damage PC12 cells and cause inflammatory reactions in nerve cells and DNA damage.astragaloside IV plays an anti-inflammatory and DNA damage protective role and inhibits the IL-17 signaling pathway to exert a neuroprotective effect in vitro.