Objective To investigate the association between birth weight and dementia risk and the mediating roles of chronic diseases,and to assess potential biological pathways underlying the birth weight-associated dementia risk based on large-scale proteomics.Methods We used data from 279 743 participants aged 40 to 69 years enrolled in the UK Biobank.Birth weight was categorized into low birth weight(≤2 500 g),normal birth weight(2 500-3 999 g),and macrosomia(≥4 000 g).Multivariable Cox proportional hazards regression models were used to assess the associations between birth weight categories and all-cause dementia and its subtypes(Alzheimer's disease and vascular dementia).Proteomics analyses were conducted to identify proteins and the potential pathways involved.Results Low birth weight was associated with higher risks for all-cause dementia and its subtypes.The hazard ratios were 1.18(95%CI,1.08-1.30)for all-cause dementia,1.14(95%CI,1.00-1.31)for Alzheimer's disease,and 1.22(95%CI,1.01-1.48)for vascular dementia.A non-linear relationship was observed between birth weight and dementia risk(P for nonlinearity<0.001).Certain cardiometabolic diseases in middle-aged adults,such as diabetes,stroke,hypertension,and dyslipidemia,played a significant mediating role in the relationship between low birth weight and dementia risk,with the mediation proportion being 6.3%to 15.8%.Proteomic analyses identified 21 proteins linked to both low birth weight and all-cause dementia risk,which were significantly enriched in the pathways for viral protein interaction with cytokines and cytokine receptors,adipocytokine signaling,and cytokine-cytokine receptor interaction.Conclusion Low birth weight is positively associated with dementia risk.Cardiometabolic diseases in middle-aged adults may mediate the relationship between low birth weight and dementia risk.A number of proteins and the associated pathways underscore the relationship between low birth weight and dementia risk.

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

Myocardial infarction is a cardiovascular disease (CVD) with high morbidity and mortality, which can trigger a cascade of cardiac pathophysiological changes, including fibrosis, inflammation, ischemia-reperfusion injury (IRI), and ventricular remodeling, ultimately leading to heart failure (HF). While conventional pharmacological treatments and clinical reperfusion therapy may enhance short-term prognoses and emergency survival rates, both approaches have limitations and adverse effects. Natural products (NPs) are extensively utilized as therapeutics globally, with some demonstrating potentially favorable therapeutic effects in preclinical and clinical pharmacological studies, positioning them as potential alternatives to modern drugs. This review comprehensively elucidates the pathophysiological mechanisms during myocardial infarction and summarizes the mechanisms by which NPs exert cardiac beneficial effects. These include classical mechanisms such as inhibition of inflammation and oxidative stress, alleviation of cardiomyocyte death, attenuation of cardiac fibrosis, improvement of angiogenesis, and emerging mechanisms such as cardiac metabolic regulation and histone modification. Furthermore, the review emphasizes the modulation by NPs of novel targets or signaling pathways in classical mechanisms, including other forms of regulated cell death (RCD), endothelial-mesenchymal transition, non-coding ribonucleic acids (ncRNAs) cascade, and endothelial progenitor cell (EPC) function. Additionally, NPs influencing a particular mechanism are categorized based on their chemical structure, and their relevance is discussed. Finally, the current limitations and prospects of NPs therapy are considered, highlighting their potential for use in myocardial infarction management and identifying issues that require urgent attention.
Humans ; Myocardial Infarction/genetics* ; Biological Products/therapeutic use* ; Animals ; Oxidative Stress/drug effects* ; Signal Transduction/drug effects*

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

Objective:Analyze the clinicopatholocical and imaging characteristics of hepatic epithelioid hemangioendothelioma (HEHE) and the related factors of survival prognosis.Methods:Clinical data of 32 patients diagnosed with HEHE at the First Affiliated Hospital of Zhengzhou University from January 2013 to December 2023 retrospectively analyzed, including 11 males and 21 females, aged (46.8±3.6) years. The clinical manifestations, pathological findings, CT and MRI features of the patients were analyzed and the living conditions of the patients were followed up. Kaplan-Meier method was used for survival analysis, and log-rank test was used for survival rate comparison.Results:Among the 32 patients, 17 (53.1%) had no obvious symptoms, 10 (31.3%) had abdominal pain, 6 (18.8%) had abdominal distension, and 4 (12.5%) had lost weight. Under the microscope, HEHE was composed of mucous matrix and epithelioid endothelial cells, with dense surrounding cells and relatively sparse center. Small blood vessels can be seen invading the junction with normal liver tissue. The positive rates of endothelial marker CD34 in immunohistochemically staining was 100%(32/32), the positive rates of CD31 were 100% (32/32). The positive rates of erythroblast transformation specific related gene were 100% (28/28), and the positive rates of Friend leukemia virus integration protein 1 (22/22) were 100%. CT and MRI scan showed that the lesion were mainly multiple nodules and in diffuse formality. In arterial phase, the lesion showed slight homogeneous or ring-like enhancement, while in portal phase, the lesion showed progressive enhancement. Some lesions may exhibit more specific "lollipop sign" ( n=9) and "target ring sign" ( n=15). The median overall survival time of the 32 patients was 47 months, and the cumulative 1-, 3-, and 5-year survival were 100%, 95.0% and 72.7%, respectively. The cumulative survival rate of patients with "target ring sign" ( n=15), extrahepatic organ involvement or metastasis ( n=8) and Ki-67 positive rate >5% ( n=10) were lower than those without the above characteristics (all P<0.05). Conclusion:The clinical manifestations of HEHE were not typical, and the tumor was rich in mucus matrix and epithelioid endothelial cells, expressing endothelial markers. CT and MRI scan mainly showed multiple nodules or diffused lesion, and the "lollipop sign" and "target ring sign" were helpful for diagnosis. HEHE patients with Ki-67 positivity rate >5%, "target ring sign", and extrahepatic organs involvement or metastasis had a poor prognosis.

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 investigate outpatients with central venous catheters regarding their awareness and needs for internet-based nursing clinics for venous catheter maintenance, and to provide reference for the development of internet-based catheter care services.Methods:A convenience sampling method was used to recruit 280 patients with central venous catheters who visited the Outpatient Catheter Maintenance Room of Beijing Friendship Hospital, Capital Medical University, between November and December 2024. A self-designed questionnaire on awareness and needs regarding catheter venous catheters in internet-based nursing clinics was used to conduct the survey.Results:A total of 280 questionnaires were distributed and 271 valid questionnaires were recovered, yielding an effective response rate of 96.79%. Regarding awareness, 47.97% (130/271) of the patients were aware of internet-based catheter maintenance services, and 80.81% (219/271) expressed willingness to try them. Regarding outpatient demand, 62.73% (170/271) preferred video consultations and 20.66% (56/271) preferred online text-based consultations. A total of 55.35% (150/271) of patients hoped for 24-hour access to consultation services, and 49.45% (134/271) were very willing to pay additional service fees. In terms of service content, 86.72% (235/271) hoped for more convenient home-visit services, 91.14% (247/271) expected assistance with expert appointment booking, and 95.94% (260/271) wanted medication delivery services related to catheter maintenance. Regarding education and support, 83.76% (227/271) hoped to gain knowledge about disease prevention and management, and 73.80% (200/271) desired guidance on healthy lifestyle practices.Conclusions:Outpatients with central venous catheters have relatively low awareness of internet-based nursing clinics for venous catheter maintenance, but show high levels of service demand. They also express expectations for expanded service content and formats. Hospital administrators should gradually improve the service system based on patients' needs and enhance educational initiatives to improve patient awareness, ultimately delivering more timely, high-quality, and efficient nursing services.

Objective:To assess cognitive impairment in children with obstructive sleep-disordered breathing (OSDB) using event-related potentials (ERPs).Methods:This case-control study analyzed data from 143 OSDB children[94 males, 49 females, aged 9.0(7.0-11.0) years] scheduled for adenotonsillectomy at the Department of Otolaryngology-Head and Neck Surgery, Beijing Tsinghua Changgung Hospital, Tsinghua University, between June 2023 and September 2024, along with 17 healthy controls [control group: 10 males, 7 females, aged 10.0 (7.5-12.0) years]. Based on polysomnography results, OSDB children were divided into a mild group [obstructive apnea-hypopnea index (OAHI)≤5 events/hour, 49 males, 29 females, aged 9.0 (7.0-10.0) years] and a moderate-to-severe group [OAHI>5 events/hour, 45 males, 20 females, aged 9.0 (8.0-10.0) years]. All children completed a face perception integration task. The occipital P100 and parietal, central and frontal P300 components of incomplete face stimuli (S1) and complete face stimuli (S2) were recorded. Amplitude and latency differences across groups were analyzed. Intergroup comparisons were performed using ANOVA, while independent samples t-tests were used for pairwise comparisons. Non-normally distributed data were analyzed using the Mann-Whitney U test. Results:(1) P100: Both the mild group [occipital P100 amplitude: O1-S1(12.44±5.96) μV, O2-S1(14.19±6.39) μV, O2-S2(30.34±11.30) μV] and moderate-to-severe group [O1-S1 (12.12±5.58) μV, O2-S1 (14.08±5.48) μV, O2-S2(29.12±10.89) μV] showed significantly higher amplitudes than the control group [O1-S1(8.46±4.74) μV,O2-S1(9.68±3.70) μV,O2-S2(23.09±9.16) μV] ( F=3.501, 4.486, 3.072; all P<0.05). No significant differences were found between the two OSDB subgroups ( P>0.05), suggesting compensatory neuronal hyperactivity maintaining normal perceptual function. The moderate-to-severe group exhibited significantly prolonged P100 latency [O2-S1 (134.52±13.42) ms] compared to controls [O2-S1 (125.18±15.31) ms] ( F=3.156 , P<0.05), while no significant difference was observed between the mild group and either the control or moderate-to-severe groups ( P>0.05), indicating delayed visual processing in severely affected children. (2) P300: The mild group exhibited significantly higher P300 amplitudes in parietal regions [P4-S1(8.22±4.32) μV, P4-S2(17.67±9.42) μV] compared to controls [P4-S1 (4.84±2.89) μV, P4-S2 (13.19±7.23) μV] ( F=7.19, 4.771; both P<0.05), whereas no significant differences were observed between the moderate-to-severe group and either the control or mild groups ( P>0.05), indicating mild group reduced alertness. The latency of P300 in the central region showed an increase in the mild group, although not significantly ( P>0.05), indicating a potential decrease in attentional response speed. However, the moderate-to-severe group demonstrated significantly shorter P300 latencies [CZ-S1(394.18±89.12) ms] compared to the mild group [CZ-S1 (433.33±100.33) ms] ( F=3.145, P<0.05), possibly reflecting compensatory enhancement of attentional engagement in more severe cases. Conclusion:Children with OSDB exhibit impairments in primary visual processing and attentional regulation, as evidenced by altered ERP components such as P100 and P300. These findings suggest that OSDB may affect neural mechanisms underlying sensory integration and executive functioning.

The triple energizer is the pathway for the transportation and metabolism of qi,blood and body fluid in the body,and the xuanfu(sweat pores)is the way for the ascending,descending,exiting,and entering of qi movement in the muscular striae and the exterior.Professor Li Huilin believes that the pathogenesis of acne is usually due to the dysfunction of triple energizer and the stagnation of depressed yang-heat,which result into the abnormal opening and closing of the xuanfu and the accumulation of heat-toxin in the muscular striae.For the treatment of acne with traditional Chinese medicine,it is necessary to pay attention to the regulation of triple energizer-xuanfu.The treatment should be based on unblocking therapy,and the therapeutic principle of unblocking triple energizer and opening xuanfu should be taken into account.In clinical practice,it is necessary to identify the syndromes of upper energizer,middle energizer and lower energizer.The syndrome of the upper energizer is often due to fire-heat,which results from the wind-heat in lung meridian or the exuberance of heart fire.The upper-energizer syndrome can be treated by the therapy of relieving and clearing the pathogens with light and mild drugs,expelling fire-heat to open sweat pores,and through the modified use of Mahuang Lianqiao Chixiaodou Decoction,Ma Xing Shi Gan Decoction,or Puji Xiaodu Decoction.The syndrome of the middle energizer is usually due to the qi stagnation,which results from intense stomach-heat,damp-heat in the spleen and stomach,liver depression and qi stagnation,or spleen deficiency with dampness accumulation.The middle-energizer syndrome can be treated by the therapy of regulating qi movement to relieve stagnation and open sweat pores,and through the modified use of Qingwei san,Sanren Decoction,Huanglian Wendan Decoction,Chaihu Shugan Powder,or Heqi Powder.The syndrome of the lower energizer is often due to healthy-qi deficiency,which results from yin deficiency of liver and kidney,or deficiency-cold in lower energizer.The lower-energizer syndrome can be treated by the therapy of cultivating the vital essence and consolidating vital base,supplementing deficiency to open sweat pores,and through the modified use of Liuwei Dihuang Pills or Yanghe Decoction.