Alzheimer's disease(AD)is a multifactorial condi-tion characterized by the accumulation of toxic proteins and asso-ciated neurodegeneration.AD is distinguished by the pathologi-cal aggregation of amyloid beta(Aβ)and Tau proteins.The in-teraction between Aβ and Tau can further induce neuroinflamma-tion,mitochondrial autophagy dysfunction,and endoplasmic retic-ulum stress,exacerbating synaptic damage and neuronal death.Neuronal cells are particularly susceptible to protein misfolding due to an imbalance between protein production and degrada-tion.The ubiquitin/26S proteasome system(UPS),a major pathway for protein degradation in eukaryotic cells,plays a cruci-al role in recognizing misfolded or damaged proteins within the nervous system.In UPS,the levels of ubiquitin are tightly regu-lated by both ubiquitin ligases(E3s)and deubiquitylases(DUBs).This article reviews the involvement and mechanisms of E3s and DUBs in the pathogenesis of AD,aiming to provide novel research strategies for its treatment.

Heatstroke,especially in high-temperature and high-humidity environments,is a life-threatening acute heat-injury disease that seriously endangers human health.Timely and effective on-site treatment is crucial for patients'survival and prognosis.Early recognition,rapid assessment,and on-site cooling are the core of pre-hospital treatment of heatstroke.Currently,there is a lack of standardized application procedures for pre-hospital emergency care of heatstroke.Therefore,the"Expert Consensus on Pre-hospital Emergency Management of Heatstroke(2024 edition)"was initiated by the Expert Group on Heatstroke Prevention of the People's Liberation Army and developed in collaboration with experts from local pre-hospital emergency care,emergency departments,and intensive care units.This consensus focuses on heatstroke prevention,on-site and ambulance-based treatment,and early emergency room interventions,and puts forward 10 evidence-based recommendations,aiming to provide a reference for scientific and standardized pre-hospital emergency care of heatstroke.

Objective:To explore the potential categories and influencing factors of medication compliance in patients with cardiometabolic multimorbidity, and provide a reference for formulating targeted intervention measures.Methods:A cross-sectional study design was adopted. From March to October 2024, the patients with cardiometabolic multimorbidity in the First Hospital Affiliated with Hunan Normal University (Hunan Provincial People′s Hospital) were selected by convenience sampling method as research objects. Data were collected using a general information questionnaire, Medication Adherence Rating Scale (MARS), Perceived Social Support Scale (PSSS), and Medication Literacy Questionnaire. The latent class analysis was used to explore the characteristics and classifications of medication compliance in cardiometabolic multimorbidity, and unordered multivariate Logistic regression was used to analyze the influencing factors of different latent classes.Results:A total of 421 subjects were included, consisting of 291 males and 130 females, aged (64.28±9.74) years old. The overall medication adherence score was 6.00 (5.00, 8.00) points, which could be divided into four categories: overall good adherence group (24.47%, 103/421), subjective perception-poor adherence group (15.91%, 67/421), forgetfulness-poor adherence group (37.53%, 158/421), and overall poor adherence group (22.09%, 93/421). The results showed that when taking the overall good adherence group as a reference, the inability to obtain pharmaceutical information from social media, medication literacy scores, social support scores were the influencing factors for the subjective perception-poor adherence group ( OR=4.210, 0.516, 0.733, all P<0.05). Occupational characteristics (employees in public institutions or government-affiliated institutions), age, social support scores were the influencing factors for the forgetfulness-poor adherence group( OR=0.173, 1.155, 0.781, all P<0.05). Occupational characteristics (employees in public institutions or government-affiliated institutions), failure to receive medication guidance from medical staff, medication literacy scores and social support scores were the influencing factors for the overall poor adherence group( OR values were 0.136-5.275, all P<0.05). When taking the overall poor adherence group as a reference, failure to receive medication guidance from medical staff and medication literacy scores were the influencing factors for the subjective perception-poor adherence group ( OR=0.310, 1.752, both P<0.05). Failure to receive medication guidance from medical staff, age, medication literacy scores and social support scores were the influencing factors for the forgetfulness-poor adherence group ( OR values were 0.315-2.554, all P<0.05). Conclusions:There is significant heterogeneity in medication adherence among patients with cardiometabolic multimorbidity. Healthcare professionals should consider individual characteristics in clinical practice and provide targeted, precise interventions to improve adherence in different patient categories.

Objective:To summarize the current status and research hotspots in volume management among patients with heart failure, and to predict future research trends.Methods:Literature related to volume management in heart failure patients published between January 1, 2004 and August 1, 2024 was retrieved from the China National Knowledge Infrastructure and Web of Science Core Collection databases. CiteSpace software was used to perform visual analysis of publication volume, authors, institutions, countries, and keywords.Results:A total of 5 008 articles were retrieved, of which 145 were Chinese and 202 were English publications. The overall publication trend showed a steady increase over the past two decades. The most prolific author was Fudim (7 publications), the leading institution was Mayo Clinic (14 publications), and the country with the highest output was the United States (91 publications). Keyword co-occurrence, clustering, and burst detection analyses revealed that current research hotspots in both Chinese and English literature mainly focus on the management and control of volume overload, exploration of nursing strategies, and patient self-management and home-based rehabilitation. Emerging trends include out-of-hospital volume overload control and intelligent volume management technologies.Conclusions:Research on volume management in heart failure patients is evolving toward diversification and integration. Clinical interventions and standardized guidelines have gained increasing attention. Home-based volume management and overload control continue to be key areas of interest. In the future, the integration of artificial intelligence and the development of individualized home self-management programs will likely become important directions to improve the quality of life in patients with heart failure.

Objective:To analyze the clinical characteristics of patients with chronic obstructive pulmonary disease (COPD) complicated by fatigue.Methods:COPD patients enrolled in the RealDTC study from June 2023 to March 2024 were included. Demographic data, history of acute exacerbations in the past year, smoking status, biofuel exposure, occupational exposure, modified Medical Research Council (mMRC) dyspnea score, COPD Assessment Test (CAT) score, forced expiratory volume in the first second predicted of percentage (FEV 1%pred), forced expiratory volume in one second (FEV 1)/forced vital capacity (FVC), and comorbidities (bronchial asthma, bronchiectasis, tuberculosis, cardiovascular disease, diabetes mellitus) were collected. Fatigue was evaluated using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) questionnaire, with a score ≤43 defined as fatigue. Patients were divided into fatigue and non-fatigue groups, and multivariate regression analysis was used to screen factors associated with fatigue in COPD patients. Results:A total of 597 COPD patients were included, of which 280(46.9%) had fatigue symptoms. Compared with non-fatigue patients, fatigue patients had lower FEV 1%pred, FEV 1/FVC, and body mass index (BMI), higher CAT and mMRC scores, and a higher proportion of occupational exposure, bronchiectasis, and treatment with long-acting β 2-agonists (LABA)/long-acting muscarinic antagonists (LAMA)/inhaled corticosteroids (ICS) (all P<0.05). Multivariate regression analysis showed that high CAT score ( OR=2.312, 95% CI: 1.366-3.911), high mMRC score ( OR=1.484, 95% CI: 1.053-2.091), occupational exposure ( OR=1.513, 95% CI: 1.082-2.116), comorbid bronchiectasis ( OR=2.452, 95% CI: 1.102-5.457), low BMI ( OR=0.935, 95% CI: 0.891-0.981), and high CAT-energy score ( OR=1.301, 95% CI: 1.149-1.473) were risk factors for fatigue in COPD patients. The CAT-energy score was highly correlated with the FACIT-F score ( r=0.260, P<0.001), and a CAT-energy score ≥2 could preliminarily screen COPD patients with fatigue. Conclusions:COPD patients with comorbid fatigue have a heavy symptom burden, are more likely to have a history of occupational exposure and bronchiectasis, and the CAT-energy score is of great reference value for screening COPD patients with fatigue.

Objective:To analyze the clinical characteristics of patients with chronic obstructive pulmonary disease (COPD) complicated by anorexia.Methods:This cross-sectional study included patients registered in the RealDTC study from May 2023 to December 2023. Demographic data, COPD Assessment Test (CAT) score, modified Medical Research Council (mMRC) dyspnea questionnaire score, Clinical COPD Questionnaire (CCQ) score, forced expiratory volume in one second (FEV 1), forced expiratory volume in the first second predicted of percentage (FEV 1%pred), FEV 1/forced vital capacity (FVC), Global Initiative for Chronic Obstructive Lung Disease (GOLD) grade, GOLD group, number of acute exacerbations and hospitalizations in the past year, and score of the Functional Assessment of Anorexia Cachexia Therapy-Anorexia/Cachexia Subscale-12 (FAACT-A/CS-12) were collected. Patients with a FAACT-A/CS-12 score ≤30 were diagnosed as having anorexia. Multivariate logistic regression analysis was used to evaluate the influencing factors of anorexia in COPD patients. Results:A total of 617 COPD patients were included, of whom 109(17.7%) had anorexia. Compared with non-anorexia patients, COPD patients with anorexia had higher age, CAT, mMRC and CCQ scores, and more acute exacerbations and hospitalizations in the past year, while body mass index, FEV 1, FEV 1%pred and FEV 1/FVC were lower (all P<0.05). The proportions of patients with primary education or below, GOLD 3-4 grade and GOLD E group were higher in COPD patients with anorexia (all P<0.05). Logistic regression analysis showed that a CAT score of 10-<20 [odds ratio ( OR)=4.017, 95% confidence interval ( CI): 1.673-59.645], a CAT score of 20-<30 ( OR=9.686, 95% CI: 3.777-24.842), a CAT score of ≥30 ( OR=78.286, 95% CI: 7.654-800.689) and ≥1 hospitalization in the past year ( OR=2.050, 95% CI: 1.292-3.254) were independent risk factors for anorexia in COPD patients (all P<0.05). Conclusions:COPD patients with anorexia have poor lung function, high symptom burden and high risk of acute exacerbation. Clinicians should pay attention to the management of COPD patients with anorexia and take corresponding intervention measures.

Objective:To analyze the clinical characteristics of frailty in elderly patients with chronic obstructive pulmonary disease (COPD).Methods:COPD patients aged ≥65 years registered in the RealDTC study from June 2023 to March 2024 were included. Demographic data, history of exacerbations in the past year, exposure to risk factors (smoking, biomass fuel exposure, occupational exposure), modified Medical Research Council (mMRC) dyspnea score, COPD Assessment Test (CAT) score, forced expiratory volume in the first second predicted of percentage (FEV 1%pred), forced expiratory volume in one second (FEV 1) to forced vital capacity (FVC), and comorbidities (bronchial asthma, bronchiectasis, pulmonary tuberculosis, cardiovascular disease, diabetes mellitus) were collected. According to Fried′s frailty phenotype, patients meeting any 3 of the 5 criteria were defined as frail and divided into a frailty group and a non-frailty group. Multivariate regression analysis was used to screen the related factors of frailty in elderly COPD patients, and the receiver operating characteristic (ROC) curve was used to calculate the area under the curve (AUC) of related factors for frailty assessment. Results:A total of 496 elderly COPD patients were included, of which 144(29.0%) had comorbid frailty. The frailty group had lower mass body index (BMI), FEV 1%pred, and FEV 1/FVC, higher mMRC and CAT scores, more exacerbations and hospitalizations in the past year (all P<0.001), and higher proportions of patients with junior high school education or below, Global Initiative for Chronic Obstructive Lung Disease (GOLD) group E, and GOLD grades 3 and 4 (all P<0.05). Multivariate regression analysis showed that low education level ( OR=2.117, 95% CI: 1.119-4.003), low BMI ( OR=0.927, 95% CI: 0.867-0.991), GOLD grade 4 ( OR=4.251, 95% CI: 1.477-12.235), high CAT score ( OR=1.174, 95% CI: 1.127-1.224), and high mMRC score ( OR=4.578, 95% CI: 3.364-6.231) were independent risk factors for frailty in elderly COPD patients (all P<0.05). The ROC curve showed that CAT score (AUC=0.78) and mMRC score (AUC=0.81) had the highest AUC for assessing frailty in elderly COPD patients. Conclusions:Elderly COPD patients with frailty have lower BMI, worse lung function, and more severe symptom burden. The results provide clinical reference for the management of frail elderly COPD patients.

This study investigated the impact of metabolic syndrome (MetS) and its components on prostate volume (PV) in the general Chinese population. In total, 43 455 participants in The First Medical Center of the Chinese PLA General Hospital (Beijing, China) from January 1, 2012, to December 31, 2022, undergoing health examinations were included in the study. Participants were categorized into four groups according to PV quartiles: Q1 (PV ≤24.94 ml), Q2 (PV >24.94 ml and ≤28.78 ml), Q3 (PV >28.78 ml and ≤34.07 ml), and Q4 (PV >34.07 ml), with Q1 serving as the reference group. Logistic regression analyses were used to examine the association between MetS and PV, with subgroup analyses conducted by age. Among the participants, 18 787 (43.2%) were diagnosed with MetS. In the multivariate analysis model, a significant correlation between MetS and PV was observed, with odds ratios (ORs) increasing as PV increased (Q2, OR = 1.203, 95% confidence interval [CI]: 1.139-1.271; Q3, OR = 1.300, 95% CI: 1.230-1.373; and Q4, OR = 1.556, 95% CI: 1.469-1.648). Analysis of MetS components revealed that all components were positively associated with PV, with abdominal obesity showing the most significant effect. The number of MetS components was identified as a dose-dependent risk factor for elevated PV. The impact of MetS, its components, and component count on PV exhibited a decreasing trend with advancing age. Overall, the influence of MetS, its components, and component count on PV was predominantly observed in the age groups of 40-49 years and 50-59 years. Early intervention targeting MetS can significantly alleviate the increase in PV, particularly benefiting individuals aged 40-59 years who have abdominal obesity.
Humans ; Male ; Metabolic Syndrome/complications* ; Middle Aged ; Cross-Sectional Studies ; Aged ; Prostate/diagnostic imaging* ; Adult ; Age Factors ; Organ Size ; China/epidemiology* ; Obesity, Abdominal ; Risk Factors

Objective To investigate the mechanism by which Senegenin(SEN)alleviates microglial inflammatory response through the nuclear factor erythroid 2-related factor 2(Nrf2)/NOD-like receptor protein 3(NLRP3)pathway.Methods BV2 mouse microglia cells were randomly divided into control group,model group,SEN group and MCC950 group.Cells in control group were not treated,and cells in model group were added with 1 μg/ml lipopolysaccharide(LPS);Cells in SEN group were added with 1 μg/ml LPS+4 μmol/L SEN,and cells in MCC950 group were added with 1 μg/ml LPS+10 μmol/L MCC950 for 24 hours.CCK-8 method was used to detect the effect of different concentrations of SEN on the viability of BV2 cells.Griess method was used to determine the release amount of nitric oxide(NO)in the supernatant.Real-time fluorescent quantitative PCR was used to determine the mRNA expression levels of NLRP3,lymphocyte apoptosis-associated spect-like protein containing a CARD(ASC),caspase-1,interleukin(IL)-1β and IL-18 mRNA.Immunofluorescence staining was used to detect the expression levels of ASC,IL-1β,Nrf2 and heme oxygenase-1(HO-1).Western blotting was used to detect the expression levels of NLRP3,caspase-1,ASC,IL-1β,IL-18,Nrf2,HO-1,nuclear factor kappa B(NF-κB)and inducible nitric oxide synthase(iNOS).Results The results of CCK-8 method showed that there was no significant difference in the viability of BV2 cells treated with 2～20 μmol/L SEN compared with control group(P>0.05).Compared with control group,the viability of BV2 cells in model group decreased significantly(P<0.05).Compared with model group,the viability of BV2 cells in 4 μmol/L SEN group was significantly restored(P<0.05).Compared with control group,the results of Griess method showed that the release amount of NO in cells of model group increased significantly(P<0.05);the results of real-time PCR showed that the expression levels of NLRP3,ASC,caspase-1,IL-1β and IL-18 mRNA in cells of model group increased significantly(P<0.05);the results of Western blotting showed that the protein expression levels of NLRP3,ASC,caspase-1,IL-1β and IL-18 proteins in cells of model group increased significantly(P<0.05),and the immunofluorescence staining results showed that the expression levels of iNOS and NF-κB protein in cells of model group increased,and the expression levels of Nrf2 and HO-1 decreased,with statistically significant differences(P<0.05).Compared with model group,the release amount of NO in cells of SEN group and MCC950 group decreased,and the expression levels of NLRP3,ASC,caspase-1,IL-1β and IL-18 mRNA and proteins decreased,with statistically significant differences(P<0.05);in the SEN group,the expression levels of iNOS and NF-κB decreased,and immunofluorescence staining showed that Nrf2 was translocated into the nucleus,and the expression levels of Nrf2 and HO-1 proteins increased significantly,with statistically significant differences(P<0.05).Conclusions SEN could alleviate the inflammatory response of mouse microglia cells induced by LPS and inhibit the activation and expression of NLRP3 inflammasome,with an effect comparable to that of the inflammasome inhibitor MCC950.The mechanism may be related to the regulation of the expression of upstream factors Nrf2 and HO-1.

Heat stroke is a heat-related illness caused by an imbalance between the body's heat production and heat dissipation,which could lead to multiple organ dysfunction syndrome with a high mortality rate.Rapid and effective reduction of core body temperature is key to successful treatment.This article reviews recent progress in the treatment of heat stroke,including new understandings of organ injury mechanisms,the timing,velocity and goals of cooling treatment,evaluation and selection of traditional cooling techniques(such as cold water immersion),and scientific evaluation of new cooling technologies(such as blood purification technology and intravascular heat exchange cooling technology),aiming to promote understanding and treatment of heat stroke.