Faced with the global challenges of population aging and a surge in dementia cases, healthcare models worldwide are undergoing profound transformation. The Netherlands' "dementia villages" concept simulates living environments, with their antipsychotic drug usage rate (11%) being significantly lower than in traditional facilities (52%). Japan has established over 12,000 "small-scale multi-functional" care facilities, striving to achieve "life in the community." Meanwhile, China is promoting community-embedded elderly care models, exemplified by Shanghai's plan to increase the number of daycare centers from 720 in 2019 to 919 by 2024, establishing a "15-minute elderly care circle." This commentary compares the Netherlands, Japan, and China across four dimensions: aging trends, innovative care models, the development of multifunctional healthcare systems, and end-of-life care philosophies. It assesses current policy developments and practical challenges, proposing that future sustainable care systems should integrate healthcare with community resources, institutional frameworks with ethical considerations, technological advancements with humanistic values, and education on death with the preservation of life with dignity.

Implantable artificial retinas have been a considerable technology to help blind people recover their sight. This topic has attracted increasing attention from both patients and clinicians because of the refractory nature of degenerative retinal diseases. A point worth noting is that artificial retinas are conventionally considered to be a tool to help blind patients recover their sight. With the development of materials and sensors, however, such devices might have characteristics of augmented reality that are beyond the capabilities of the natural eye. This study briefly summarizes the current clinical status of implantable artificial retinas, it explores emerging technologies that aim to augment vision, and it discusses the challenges that must be overcome before these devices can be further used clinically. Indeed, the implantation of such advanced retinal prostheses with augmented reality characteristics may bring about new ethical and legal risks that warrant further consideration.

Aging of the population has become a critical challenge globally. The proportion of individuals age 60 years and older is projected to increase from 12% in 2015 to 22% by 2050, representing more than 2.1 billion older adults globally. This demographic transition is advancing particularly rapidly in Japan, which has become the first nation to become a "super-aged society". Projections indicate that by 2060, the number of older adults living with dementia will reach approximately 6.45 million (more than 17% of the elderly population), making it one of the country's most urgent health and social care challenges. Japan has developed a comprehensive response system that integrates medical, community, and family-based care. Key initiatives include a national dementia strategy, mechanisms for early screening and diagnosis, the establishment of memory clinics, and the implementation of the community-based integrated care system, which emphasizes coordination between healthcare and long-term care services. These measures have alleviated part of the burden on patients and families while enhancing social awareness of dementia and inclusion of those with that condition. Nevertheless, Japan continues to face significant structural challenges, such as severe shortages of healthcare personnel and professional caregivers, increasing fiscal pressure on long-term care financing, insufficient dissemination of innovative therapies and digital diagnostic tools, and disparities in social support between urban and rural areas. Cross-national comparisons indicate that Japan's experience offers valuable lessons for other rapidly aging societies, particularly in policy design, the integration of community-based care, and the promotion of a dementia-inclusive society. Summarizing and adapting Japan's approaches may therefore provide globally applicable strategies to build sustainable and equitable systems for dementia prevention, management, and care.

With the accelerating trend of population aging, Japan has become the first country to enter a "super-aged society", where the proportion of people age 65 and over exceeds 21%, making it a global model in addressing aging-related challenges. In response to the various social and healthcare issues arising from this demographic shift, the Japanese Government has implemented a series of policy measures. Among them, "Small-scale Multifunctional In-home Care (Shotaki)" and "Nursing Small-scale Multifunctional In-home Care (Kantaki)" have emerged as key components of the community-based care system. This paper explores the common challenges faced in super-aged populations and provides a comparative analysis of the functions, current status, existing issues, and future prospects of "Shotaki" and "Kantaki". By examining these two service models, the study aims to offer policy recommendations and practical insights to build a sustainable elderly care system.

Against the backdrop of accelerating global population aging, China is undergoing significant demographic shifts. Its population aged 60 and above has reached 264 million, projected to account for 40% of the total population by the mid-21st century, becoming a "super-aging society" and triggering a surge in long-term care demand. On the demand side, the overall ADL disability rate among middle-aged and older adults is 23.8% (35.4% organic), rising to 30.5% among those aged 80 and above; 17.8% have IADL impairments, and 36.44% of households with older adults are empty-nest. Combined with population aging, rising disability rates, the growth of empty-nest families, and heavy disease burdens, care demand continues to grow annually. On the supply side, 13 million caregivers are needed for disabled/semi-disabled older adults, with only ~1 million practitioners; traditional models focusing solely on basic daily assistance fail to meet diverse needs like mental health support and rehabilitation. To this end, this study aims to synthesize evidence on the structural challenges faced by China's geriatric care workforce. By analyzing demographic data, care demand indicators, and geriatric care models, it identifies core issues and proposes evidence-based strategies, with the purpose of improving the quality of life of older adults and strengthening development of professional geriatric care talent.

The apolipoprotein E ε4 (APOE ε4) allele, the strongest genetic risk factor for late-onset Alzheimer's disease (AD), induces cell-type-specific disturbances in brain lipid metabolism. Although impacting astrocytes and neurons, its most pronounced effects occur in microglia, where it causes energy metabolism deficits and promotes the formation of lipid droplet-accumulating microglia, triggering a cascade of neurodegenerative responses. This review comprehensively examines how microglial APOE4-driven lipid metabolic dysregulation exacerbates neuroinflammation and compromises phagocytic capacity, particularly in the clearance of amyloid-β, phosphorylated-tau, and pathological synapses. Mechanistically, microglial APOE4 activates neuroinflammation via LilrB3-mediated type I interferon signaling and induces lipid metabolic imbalance through PU.1/NF-κB-driven transcriptional reprogramming and ER stress-SREBP2 activation. These disturbances exacerbate neuroinflammation, promote lipid droplet accumulation and cholesterol overload, impair lysosomal function, and ultimately compromise microglial phagocytosis. The resulting disruption of neuron-microglia interactions further amplifies neurotoxicity in AD. Furthermore, this review summarizes emerging therapeutic strategies targeting APOE4-related pathway in microglia. By synthesizing these insights, this review highlights the multifaceted role of microglial APOE4 in AD pathology, with particular emphasis on the central role of lipid metabolism dysregulation, and provides new intervention ideas for reducing its damage to brain function.

The high performance of core members of social organizations (SOs) caring for the elderly can enhance the quality of management and services, thereby improving the life satisfaction of older adults residing there. However, the factors influencing the performance of core members and their pathways remain unclear. This research seeks to uncover how social support mediates and self-efficacy moderates the association between a social network and individual performance of core members of SOs caring for the elderly. A cross-sectional survey was conducted from June to August 2023 in Shanghai, China, and data on participants' demographics, social network, social support, individual performance, and self-efficacy were collected. Hierarchical stepwise regression, bootstrap analysis, and simple slope method analysis were used to test potential mediating and moderating effects. After adjusting for confounders, the total effect of a social network on core members' individual performance (β = 0.078, 95% CI: 0.052-0.103) consisted of a direct effect (β = 0.059, 95% CI: 0.030-0.087) as well as an indirect effect mediated through social support (β = 0.019, 95% CI: 0.006-0.033). In addition, self-efficacy was identified as a moderating factor in the relationship between a social network and individual performance, with higher levels of self-efficacy diminishing the influence of a social network on performance outcomes. An extensive social network can enhance social support for core members of SOs caring for the elderly, thereby improving individual performance. Concurrently, targeted interventions should be developed to draw on self-efficacy to activate social network resources and to have a synergistic effect on individual performance.

Colorectal liver metastasis (CRLM) remains lethal, and the convergence of cellular senescence with metabolic reprogramming via epigenomic rewiring is poorly understood. We integrated genome-wide DNA methylation and RNA-seq data from 10 paired primary tumors and liver metastases (GSE213402). After calling differentially methylated genes (3,399 hyper- and 9,519 hypomethylated) and differentially expressed genes (406 DEGs), we intersected them with curated senescence (n = 866) and metabolic reprogramming (n = 948) gene sets, yielding 28 differentially expressed cellular-senescence-related genes (DE-CSRGs) and 24 metabolic-reprogramming-related genes (DE-MRRGs). Machine-learning pipelines (LASSO + SVM-RFE) converged on a five-gene signature: CXCL1, SERPINE1, NDRG1, SRM and GATM, most of which are hypomethylated and over-expressed in metastases. Gene-set enrichment analysis revealed that these genes are involved in pathways such as oxidative phosphorylation, focal adhesion, complement–coagulation cascades, and PPAR signaling. Immune de-convolution revealed strong positive correlations between signature genes and immunosuppressive subsets (MDSCs, Tregs, type-1 T-helper cells; p < 0.05). Elevated IC₅₀ values for oxaliplatin and 5-fluorouracil in metastatic samples were positively associated with NDRG1 and negatively with SRM, indicating chemo-resistance modulation. This five-gene epigenetic–transcriptomic hub identifies a molecular signature that warrants prospective validation as a potential biomarker for patient stratification and combination therapy in CRLM.

Endometrial receptivity plays a critical role in pregnancy, while controlled ovarian hyperstimulation (COH) — widely used for infertile patients — could impair endometrial receptivity and subsequent pregnancy outcomes. This study aims to explore the effect of Yiqi Bushen Shugan Huoxue Decoction (YBSHD) on impaired endometrial receptivity in patients with unexplained infertility (UI) undergoing COH and to determine the mechanism for it through modular pharmacology, molecular docking, and a murine model. First, we retrospectively studied 422 patients with UI who underwent COH to get pregnant. Results indicated that the live birth rate significantly increased in the YBSHD group. Second, a systematic network pharmacology analysis was performed to screen the ingredients and possible targets of YBSHD. The main targets concerning YBSHD and endometrial receptivity involved pathways including hormone regulation, inflammatory responses, and apoptosis. The active components of quercetin and kaempferol from YBSHD exhibited a strong binding affinity to key molecules, including BCL2, ESR1, IL6, IL1B, and TNF. Third, YBSHD improved endometrial receptivity in a murine COH model. Compared to the COH group, the number of embryo implantations and endometrial pinopodes significantly increased in the YBSHD group, indicating improved endometrial receptivity. YBSHD improved the local immune microenvironment in COH mice by regulating excessive hormone secretion, gene expression of inflammatory factors, and proportions of neutrophils and macrophages. Moreover, YBSHD inhibited apoptosis in the ovaries and uteruses of COH mice. In summary, YBSHD could increase the live birth rate in patients with UI, mainly because it can inhibit inflammation and cell apoptosis, thereby improving endometrial receptivity.

Hearing impairments, as a prevalent and debilitating non-motor symptom of Parkinson's disease (PD), remain unclear in mechanisms. In this work, we established PD mouse and rat models by using 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 6-hydroxydopamine (6-OHDA), respectively, and investigated their hearing functions and potential mechanisms through auditory brainstem response (ABR), distortion product otoacoustic Emissions (DPOAE), noise exposure, immunofluorescence labeling, volumetric measurement, and colocalization analysis. In MPTP-induced PD mice, we observed significant cholinergic fibers decompensation, heterogeneous dopaminergic fibers damage of cochlear efferent fibers, and adrenergic sympathetic fibers marked loss in the osseous spiral lamina (OSL), corresponding to insignificant cochlear hair cells, ribbon synapse alteration, and auditory sensitivity injury. While in 6-OHDA-induced PD rats, asymmetric alterations in cochlear cholinergic, dopaminergic fibers were found, accompanied by inconsistent adrenergic changes in the OSL, which matched unilateral hair cells, ribbon synapse damage, and hearing loss. Overall, findings from this work indicate that pathological alterations in the cochlea of PD mice and rats, particularly in efferent fibers, may be closely relevant to peripheral hearing alterations.