ObjectiveTo make clear exercise combined with Shenghui Tang interferes in acetylcholine receptor （M1AChR） to improve mitochondrial autophagy and enhance cognition of Alzheimer's disease （AD） model rats through the adenylate activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR） signaling pathway. MethodsForty-eight male SD rats of SPF grade were randomly divided into a blank group， a model group， a Shenghui Tang group （9.3 g·kg^-1）， an exercise group， an exercise + Shenghui Tang group （9.3 g·kg^-1）， and a rapamycin group （1.5 mg·kg^-1）. Except for the blank group， the rat model of AD was constructed by injecting amyloid beta （Aβ_1-42） into hippocampus stereotaxically. The exercise group received treadmill exercise for 4 weeks， while the Shenghui Tang group received intragastric administration for 4 weeks， and the exercise + Shenghui Tang group received treadmill exercise and intragastric administration of Shenghui Tang for 4 weeks simultaneously. After the intervention， the Morris water maze test was used to detect the learning and memory ability. Spontaneous behavior was observed in the open field test. The pathological structure of hippocampal neurons was observed by NISSl staining. The expression level of M1AChR in hippocampus was detected by immunohistochemistry （IHC）. The autophagy ultrastructure of hippocampal neurons was observed by transmission electron microscopy. The apoptosis rate was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL）. The expression of Beclin1 and microtubule-associated protein light chain 3β （LC3β） was detected by immunofluorescence （IF）. The protein expression of M1AChR， AMPK， p-AMPK， mTOR， Beclin1， LC3β， and chelate 1 （SQSTM1/p62） in hippocampus was detected by Western blot. ResultsCompared with the blank group， the model group exhibited significantly increased platform escape latency on the fifth day （P<0.01） and significantly decreased activity distance in the target quadrant and times of crossing the platform （P<0.01）. The total movement distance in the open field， the time of movement in the central area， and the average speed obviously decreased （P<0.05）. The arrangement of nerve cells in hippocampus CA1 region was dispersed， and the numbers of Nissl bodies and M1AChR positive cells significantly decreased （P<0.01）. The expression of TUNEL positive cells was significantly increased （P<0.01）. The typical autophagic lysosomal structure decreased. The protein expression of M1AChR， p-AMPK/AMPK， p-mTOR/mTOR， Beclin1， LC3Ⅱ/Ⅰ in hippocampus was significantly decreased （P<0.01）， and the protein expression of p62 was significantly increased （P<0.01）. Compared with the model group， the exercise + Shenghui Tang group exhibited obviously improved space exploration and positioning navigation ability （P<0.05， P<0.01）. The total movement distance in the open field， the time of movement in the central area， and the average speed of movement significantly increased （P<0.01）. The number of Nissl bodies significantly increased （P<0.01）. The number of M1AChR positive cells in hippocampus was significantly increased （P<0.01）. The expression of TUNEL positive cells was significantly decreased （P<0.01）. The protein expression of M1AChR， p-AMPK/AMPK， p-mTOR/mTOR， Beclin1， LC3Ⅱ/Ⅰ in hippocampus was significantly increased （P<0.01）， while the protein expression of p62 was significantly decreased （P<0.01）. Compared with the exercise + Shenghui Tang group， the Shenghui Tang group and the exercise group showed significantly increased platform escape latency on the fifth day （P<0.01） and obviously decreased activity distance in the target quadrant and times of crossing the platform （P<0.05， P<0.01）. The total movement distance in the open field， the time of movement in the central area， and the average speed of movement significantly decreased （P<0.01）. The number of Nissl bodies and the number of M1AChR positive cells significantly decreased （P<0.01）. The expression of TUNEL positive cells was obviously increased （P<0.05）. Ultrastructure of the hippocampal region showed decreased autophagy level. The protein expression of M1AChR， p-AMPK/AMPK， p-mTOR/mTOR， LC3Ⅱ/Ⅰ in the hippocampus was obviously decreased in the Shenghui Tang group （P<0.05， P<0.01）， while the protein expression of p62 was significantly increased （P<0.01）. In the exercise group， the protein expression of M1AChR， p-AMPK/AMPK， Beclin1， and LC3Ⅱ/Ⅰ was obviously decreased （P<0.05， P<0.01）， while the protein expression of p-mTOR/mTOR and p62 was significantly increased （P<0.01）. ConclusionExercise combined with traditional Chinese medicine can enhance the expression of M1AChR in the hippocampus of AD model rats， induce autophagy through the AMPK/mTOR signaling pathway， and improve the learning and memory ability of AD rats.

Programmed cell death (PCD) is characterized as a cell death pathway governed by specific gene-encoding requirements, plays crucial roles in the homeostasis and innate immunity of organisms, and serves as both a pathogenic mechanism and a therapeutic target for a variety of human diseases. Z-DNA-binding protein 1 (ZBP1) functions as a cytosolic nucleic acid sensor, utilizing its unique Zα domains to detect endogenous or exogenous nucleic acids and its receptor-interacting protein homotypic interaction motif (RHIM) domains to sense or bind specific signaling molecules, thereby exerting regulatory effects on various forms of PCD. ZBP1 is involved in apoptosis, necroptosis, pyroptosis, and PANoptosis and interacts with molecules, such as receptor-interacting protein kinase 3 (RIPK3), to influence cell fate under various pathological conditions. It plays a crucial role in regulating PCD during infections, inflammatory and neurological diseases, cancers, and other conditions, affecting disease onset and progression. Targeting ZBP1-associated PCD may represent a viable therapeutic strategy for related pathological conditions. This review comprehensively summarizes the regulatory functions of ZBP1 in PCD and its interactions with several closely associated signaling molecules and delineates the diseases linked to ZBP1-mediated PCD, along with the potential therapeutic implications of ZBP1 in these contexts. Ongoing research on ZBP1 is being refined across various disease models, and these advancements may provide novel insights for studies focusing on PCD, potentially leading to new therapeutic options for related diseases.

INTRODUCTION: Lecanemab has shown promise in treating early Alzheimer's disease (AD), but its safety and efficacy in Chinese populations remain unexplored. This study aimed to evaluate the safety and 6-month clinical outcomes of lecanemab in Chinese patients with mild cognitive impairment (MCI) or mild AD. METHODS: In this single-arm, real-world study, participants with MCI due to AD or mild AD received biweekly intravenous lecanemab (10 mg/kg). The study was conducted at Hainan Branch, Ruijin Hospital Shanghai Jiao Tong University School of Medicine. Patient enrollment and baseline assessments commenced in November 2023. Safety assessments included monitoring for amyloid-related imaging abnormalities (ARIA) and other adverse events. Clinical and biomarker changes from baseline to 6 months were evaluated using cognitive scales (mini-mental state examination [MMSE], montreal cognitive assessment [MoCA], clinical dementia rating-sum of boxes [CDR-SB]), plasma biomarker analysis, and advanced neuroimaging. RESULTS: A total of 64 patients were enrolled in this ongoing real-world study. Safety analysis revealed predominantly mild adverse events, with infusion-related reactions (20.3%, 13/64) being the most common. Of these, 69.2% (9/13) occurred during the initial infusion and 84.6% (11/13) did not recur. ARIA-H (microhemorrhages/superficial siderosis) and ARIA-E (edema/effusion) were observed in 9.4% (6/64) and 3.1% (2/64) of participants, respectively, with only two symptomatic cases (one ARIA-E presenting with headache and one ARIA-H with visual disturbances). After 6 months of treatment, cognitive scores remained stable compared to baseline (MMSE: 22.33 ± 5.58 vs . 21.27 ± 4.30, P = 0.733; MoCA: 16.38 ± 6.67 vs . 15.90 ± 4.78, P = 0.785; CDR-SB: 2.30 ± 1.65 vs . 3.16 ± 1.72, P = 0.357), while significantly increasing plasma amyloid-β 42 (Aβ42) (+21.42%) and Aβ40 (+23.53%) levels compared to baseline. CONCLUSIONS: Lecanemab demonstrated a favorable safety profile in Chinese patients with early AD. Cognitive stability and biomarker changes over 6 months suggest potential efficacy, though high dropout rates and absence of a control group warrant cautious interpretation. These findings provide preliminary real-world evidence for lecanemab's use in China, supporting further investigation in larger controlled studies. REGISTRATION ClinicalTrials.gov , NCT07034222.
Humans ; Alzheimer Disease/drug therapy* ; Male ; Female ; Aged ; Middle Aged ; Cognitive Dysfunction/drug therapy* ; Aged, 80 and over ; Amyloid beta-Peptides/metabolism* ; Biomarkers ; East Asian People

The elevated polyamines, amine-rich molecules with diverse functions in pathophysiology processes, are implicated in contributing to tumorigenesis and progression. Whether and how they affect the efficacy of chemotherapy is incompletely understood. Our screening assays reveal that the supplement with a low dose of spermidine (Spd), one of the polyamines, enhances ferroptosis in prostate cancer cells as evidenced by increased lipid peroxidation and intracellular Fe²⁺ levels in vitro. Combination treatment with Spd and a low dose of ferroptosis inducer erastin synergistically augments anti-tumor efficacy with undetectable toxicity in mice. Analysis of RNA-seq data indicates that heme oxygenase 1 (HMOX1), an enzyme that catalyzes the cleavage of heme to release Fe²⁺, is significantly upregulated in response to Spd and erastin cotreatment. Spd mediated the hypusine modification of the eukaryotic initiation factor 5A (EIF5A) promotes the translation of the nuclear factor erythroid 2-related factor 2 (NRF2), subsequently leading to elevation of HMOX1. Moreover, Spd and erastin significantly inhibit proteasome activity which results in a decrease in proteasomal degradation of NRF2, although many proteasome-related genes are induced either by Spd or Spd plus erastin. Thus, in addition to its pro-oncogenic activity, the supplement of Spd improves antitumor activity in combination with ferroptosis inducers and offers an optional approach to cancer treatment.

Nine novel compounds, comprising seven tetrahydroanthraquinones (auxarthrolones A-G, 1-7), a γ-butenolide glycoside (malfilamentoside E, 26), and a γ-butenolide (auxarthrolide A, 27), together with eighteen known compounds (8-25) were isolated from rice-based solid culture of Auxarthron umbrinum (A. umbrinum) DSM3193 using the one strain many compounds (OSMAC) approach. The structural elucidation of these compounds was accomplished through nuclear magnetic resonance (NMR), mass spectrometry (MS), and NMR calculation combined with DP4+ analysis or MAEΔΔδ parameter, while the absolute configurations of new compounds were established through single-crystal X-ray diffraction, electronic circular dichroism (ECD) spectroscopic data analysis and/or chemical derivatization. Austrocortilutein (10) and auxarthrol H (14) demonstrated moderate cytotoxicity against U87 and U251 [half maximal inhibitory concentration (IC₅₀) 3.5-12.1 μmol·L^-1]. Additionally, auxarthrolone A (1), auxarthrol H (14), eupolyphagin B (15), and 7-hydroxy-2-(2-hydroxypropyl)-5-methylchromone (17) exhibited torsional effects on fibroblast proliferation challenges induced by oleic acid, thus demonstrating fibroblast proliferation-promoting activity.
4-Butyrolactone/pharmacology* ; Molecular Structure ; Anthraquinones/pharmacology* ; Humans ; Animals ; Mice ; Cell Line, Tumor ; Magnetic Resonance Spectroscopy

As a major category of occupational hazards in China, physical factors are widely distributed in various industries and affect a large number of workers. The list and diagnostic criteria of occupational diseases caused by physical factors are important basis for occupational disease diagnosis and protection of occupational health rights and interests for occupational populations. This article compares the differences in the list of occupational diseases caused by physical factors at home and abroad, analyzes the problems in the current list of occupational diseases caused by physical factors and related diagnostic standards in China, and puts forward relevant suggestions for further adjusting the list of occupational diseases caused by physical factors, formulating and revising relevant diagnostic standards for occupational diseases, providing reference for improving the classification and catalogue of occupational diseases in China in the future.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous condition with diverse phenotypes and endotypes. The emphysema phenotype, characterized by destruction of the terminal bronchioles and alveolar walls, is associated with more severe lung function impairment, heightened airway inflammation, and greater systemic dysfunction compared to other subtypes. Early diagnosis via biomarkers, signaling pathway analysis, and imaging, combined with targeted therapies, may improve patient outcomes. However, further research is needed to fully elucidate this phenotype. This review summarizes recent advances in the pathology, biomarkers, signaling pathways, and clinical management of the emphysema phenotype of COPD, aiming to enhance its recognition and inform future research.

Objective:To analyze the operational effectiveness of a multi-medication management and consultation service platform for elderly patients based on quality function deployment (QFD) and “Internet+”.Methods:It was a non-randomized controlled trial. A total of 100 elderly patients were selected from the Department of Neurology of the First Affiliated Hospital of Wenzhou Medical University from September to November 2023 with convenience sampling method. The medication management was carried out through the multiple medication management and counseling service platform for the patients based on QFD and “Internet+”. The core modules included reminder module, evaluation module, consultation module and popularization module. A self-designed satisfaction questionnaire was used to collect the satisfaction scores of hospital service quality, medication adherence, medication knowledge, and medication safety before and one month after the platform was implemented. A total of 100 questionnaires were distributed, and 100 valid questionnaires (100%) returned. The t-test was used to analyze the differences between the satisfaction scores before and after the operation of the platform to evaluate the operation effects. Results:Among the 100 elderly patients with multiple medications included in the analysis, 65 were male and 35 were female, 84 patients had a combination of ≥2 chronic diseases. The patients aged (68.73±5.99) years, and the number of medications they were taking was (7.65±1.04). The scores of hospital service quality, medication adherence, medication knowledge, and medication safety after the application of the platform were all significantly higher than those before the launch of the platform [(3.66±0.48) vs (2.91±0.70) points, (3.90±0.30) vs (1.30±0.46) points, (3.39±0.49) vs (3.02±0.63) points, (3.75±0.44) vs (1.48±0.59) points](all P<0.05). Conclusion:The multiple medication management and consultation service platform for elderly patients based on QFD and “Internet+” can enhance the scientific management of multiple medication in elderly patients, reduce the burden of medication, improve the quality of medical services, and promote the development of intelligent elderly care services.

Objective:To investigate the prospective association between lifestyle and the risk for all-cause mortality in middle-aged and elderly residents in China.Methods:The data from China Health and Retirement Longitudinal Study were used. Baseline information about the lifestyle were collected through questionnaire survey and physical measurements, and the mortality data were obtained through surveys conducted at 2-3 year intervals. A total of 5 436 study participants were included. A comprehensive lifestyle including smoking, alcohol consumption, sleep, BMI and physical activity was constructed, and a multivariate-adjusted Cox proportional hazards regression model was used to estimate the association between lifestyle and the risk for all-cause mortality.Results:During the follow-up of average 8.2 years, 695 deaths were recorded. The comprehensive lifestyle score was linearly associated with the risk for all-cause mortality. Compared with the study participants with comprehensive lifestyle score of 0-1, those with score of 2-5 all had lower risk for all-cause mortality, with HRs of 0.78 (95% CI: 0.62-0.98), 0.56 (95% CI: 0.44-0.72), 0.36 (95% CI:0.27-0.48), and 0.33 (95% CI: 0.21-0.52), respectively. The results of Cox proportional hazards regression model analysis of single lifestyle showed that compared with those with unhealthy lifestyles, the HRs of all-cause mortality for study participants who never smoked, had moderate alcohol consumption, had appropriate night sleep, maintained healthy body weight and kept active physical activity were 0.70 (95% CI: 0.57-0.84), 0.76 (95% CI: 0.64-0.90), 0.79 (95% CI: 0.67-0.94), 0.73 (95% CI: 0.62-0.87), and 0.68 (95% CI: 0.58-0.80), respectively. Conclusions:Keeping healthy lifestyles can significantly reduce the risk for all-cause mortality in middle-aged and elderly residents China. The higher the healthy lifestyle level, the lower the risk for all-cause mortality.

Objective To identify the key influencing factors and role mechanisms of large-scale medical equip-ment allocation decision-making in public hospitals,and to provide a reference basis for optimizing resource alloca-tion strategies.Methods Through searching the literature related to large-scale medical equipment decision-making in public hospitals and combing the policies,the system of decision-making influencing factors was initially screened.The Delphi method and decision-making trial and evaluation laboratory method were used to obtain the key influencing factors of equipment allocation decision-making and to determine the interaction effects among the factors.Results A total of seven cause factors and nine effect factors were screened.Among them,cost-benefit analysis,equipment technical performance,and evaluation of similar equipment were the top three key drivers;leadership emphasis,equipment market price,and equipment supporting facilities were the top three key con-straints.Conclusion Priority be given to strengthening the management of driving factors,mainly by conducting a full-cycle assessment of cost-effectiveness,paying attention to the clinical value output of equipment technical performance,and monitoring regionally similar equipment.A dynamic response mechanism for constraints should be established,mainly to strengthen leadership decision-making,implement a centralized procurement price nego-tiation model and improve the pre-assessment system for ancillary facilities.