Neurotropin, a non-protein extract widely used for the treatment of neuropathic pain, has recently been reported to protect against ischemic brain injury, enhance remyelination in demyelinating diseases, and ameliorate neuroinflammation and memory deficits. However, its role in microglial polarization and mitochondrial dysfunction in Alzheimer's disease (AD) remains poorly understood. In this study, we investigated the therapeutic potential of Neurotropin in the 5xFAD mouse model of AD. Neurotropin administration alleviated cognitive decline, reduced amyloid-β (Aβ) deposition, suppressed neuroinflammation, and preserved neuronal density. Mechanistically, Neurotropin improved mitochondrial morphology, restored ATP production, increased mitochondrial DNA copy number, and reduced oxidative stress while promoting a shift in microglial polarization from the pro-inflammatory M1 phenotype toward the anti-inflammatory M2 phenotype. Transcriptomic and molecular analyses revealed that calcium homeostasis modulator family member 2 (Calhm2) was markedly upregulated in 5xFAD mice, colocalized with microglia, and transcriptionally regulated by fused in sarcoma (FUS), while Calhm2 interacted with EF-hand domain containing protein D2 (EFhd2). Neurotropin suppressed FUS-mediated Calhm2 transcription and attenuated Calhm2–EFhd2 interaction. Importantly, overexpression of Calhm2 in both microglial cells and 5xFAD mice abolished the beneficial effects of Neurotropin, leading to exacerbated mitochondrial dysfunction, oxidative stress, and inflammatory cytokine release. Together, these findings identify Calhm2 as a critical mediator of Neurotropin's neuroprotective effects and demonstrate that Neurotropin alleviates AD pathology by suppressing FUS-dependent Calhm2 transcription and blocking the Calhm2/EFhd2 interaction. This study provides new insights into the mechanism of Neurotropin action and highlights its therapeutic potential for AD.

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.

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.

Premature ovarian failure (POF), also referred to as premature ovarian insufficiency (POI), is a multifactorial reproductive endocrine disorder characterized by amenorrhea, infertility, hypoestrogenism, and elevated gonadotropin levels before the age of 40. Emerging evidence links its pathogenesis to oxidative stress and dysregulation of the autophagy–apoptosis balance in ovarian cells. Excessive accumulation of reactive oxygen species (ROS) impairs mitochondrial function in oocytes, while aberrant autophagy and granulosa cell apoptosis accelerate the depletion of primordial follicles. The AMP-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) pathway serves as a critical nexus between energy metabolism, oxidative stress, and cell survival. Traditional Chinese medicine (TCM), with its multi-component and multi-target characteristics, has demonstrated unique advantages in modulating the AMPK/mTOR pathway to restore ovarian function. This review synthesizes recent findings on single herbs, classical formulas, and non-pharmacological therapies (acupuncture and moxibustion). Mechanistic studies have revealed that these interventions can activate AMPK, inhibit mTOR overactivation, enhance Nrf2-mediated antioxidant defenses, reduce ROS production, and rebalance autophagy and apoptosis via pathways such as PI3K/Akt and SIRT1/p53. By aligning stage-specific regulation of AMPK/mTOR signaling with the TCM principle of syndrome differentiation, this integrative approach provides theoretical guidance for precise, personalized treatment to optimize multi-target strategies for POF management.

The persistent mutation of the novel coronavirus (SARS-CoV-2) not only remains a threat to human health but also continues to challenge existing antiviral therapeutic strategies. In current clinical practice, the resistance of novel coronavirus to antivirals, the rebound of viral load after treatment with drugs such as nirmatrelvir/ritonavir (NTV/r), and the urgent need for rapid clearance of the virus in the management of critically and emergently ill patients suggest that the existing single-drug regimens may have limitations and that the intensity of suppression may be insufficient in some cases. In clinical practice, we have observed that a combination of antivirals with different mechanisms of action can result in better efficacy and not significantly increase adverse drug reactions (ADRs). For some immunosuppressed, post-transplantation, or other special patients in particular, such as those in whom COVID-19 nucleic acids tended not to be negative after conventional treatment, when virus clearance is still the main goal, the combination of small-molecule antivirals can help to clear the virus as early as possible and attempt to improve the success rate of salvage. Based on evidence-based medicine and in light of the current situation of China, we assembled experts from disciplines such as infectious diseases, respiratory medicine, critical care medicine, and clinical pharmacy into a group to carry out a systematic literature search and identify key issues and to put forward relevant recommendations to reach an Expert Consensus on Combined Use of Oral Small-molecule Antivirals to Treat COVID-19, which is intended to serve as a reference for clinical practice.

On May 5, 2023, the WHO declared that the COVID-19 pandemic no longer constitutes a public health emergency of international concern (PHEIC), but SARS-CoV-2 continues to spread and evolve on a global scale. The WHO reported that COVID-19 still poses a threat to humanity, and especially in some areas with large numbers of infected people. For some high-risk COVID-19 patients, such as those with underlying conditions, elderly patients, patients who need long-term immunosuppressive therapy after organ transplantation, patients with immunosuppressive diseases, patients who tend not to test negative for SARS-CoV-2 despite standard antiviral therapy, and cancer patients, special attention is still required after infection with SARS-CoV-2. How to clear SARS-CoV-2 in a timely manner is the key to treating such patients. Based on the demands of clinical practice and medical evidence, the National Center for Infectious Diseases of China assembled experts from relevant disciplines to reach the Chinese expert consensus on the combined use of antivirals to treat COVID-19, providing timely suggestions to resolve the medication issues that have been plaguing clinical practice. The consensus suggests that for special patients, combined medication can promptly eliminate the virus without increasing the risk to patient safety.

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 medical metaverse, with its potential for efficient care delivery, improved patient outcomes, and reduced healthcare costs, is profoundly impacting global healthcare systems. Scholars researching this topic primarily focus on exploring specific scenarios for its use. This article aims to analyze the development trajectory, potential applications, and directions for management optimization within the medical metaverse. Through a case study of China, we review the current status of use of the medical metaverse and systematically examine its future prospects and challenges. We contend that the medical metaverse offers significant value in enabling equitable distribution of healthcare resources, enhancing medical care efficiency, promoting the integration of medical education, research, and clinical practice, and assisting in public health management. To ensure sustainable development, however, the imperative task is to proactively devise technical standards and legal regulatory frameworks and to dynamically monitor the effectiveness of medical metaverse technologies, with the ultimate aim of maximizing the value of the medical metaverse.

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.

Early-stage diagnosis offers the greatest survival advantage in oncology, and yet conventional liquid-biopsy markers — circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs) — depend on cell death or mechanical shedding and therefore appear late in disease progression. Exosomes, 40–160 nm lipid-bilayer vesicles secreted by viable cells, emerge earlier, outnumber CTCs by several orders of magnitude, and preserve multi-omic cargo that mirrors intratumor heterogeneity. Rapid advances in enabling technologies are driving continual breakthroughs in exosome-based liquid biopsy, laying a solid foundation for its accelerated translation into clinical practice. Key hurdles remain: standardizing exosome isolation, defining quantitative cut-offs that separate malignant from inflammatory EV surges, and building probabilistic multi-omic models to pinpoint tissue origin. Eliminating these obstacles could advance detection by months and shift care from late salvage to true early interception.

Effective antiretroviral therapy (ART) depends on adequate drug exposure. Plasma ART concentrations provide a short-term assessment of drug exposure, and hair promises to be an alternative matrix for measuring long-term exposure. We aimed to determine the association between plasma and hair ART concentrations and explore the therapeutic concentrations in hair. A cohort study in which HIV-infected adults receiving tenofovir disoproxil fumarate (TDF) + lamivudine (3TC) + efavirenz (EFV) regimen for at 6 months were recruited and paired hair and plasma samples collected at about 6±1 months of ART. Previously validated liquid chromatography and tandem mass spectrometry methods were used to measure ART concentrations in plasma and hair. Among 74 participants enrolled, 47 used a 400 mg dose of EFV daily and 27 used 600 mg EFV daily. Hair and plasma EFV concentrations were strongly correlated, with particularly strong association observed in the 600 mg EFV group. The hair EFV concentration of female participants was significantly higher than in male participants, which might be the inter-individual variations in the drug metabolism and dissolution and life habits. The concentrations of TDF and 3TC in hair are too low to determine effective threshold and relationship with plasma drugs concentrations. The accumulation and correlation of hair and plasma EFV concentrations promise to determine a therapeutic range in hair. The therapeutic range for EFV in hair needs to be calculated in order to give quantitative results more value within the field of drug exposure assessment.

Treatments for solid tumors, the most common malignant neoplasms, are often confounded by tumor microenvironments that impede the achievement of uniform anti-tumor effects throughout the entire malignant mass, which contributes to recurrence and progression, negatively impacting clinical outcomes. Improved treatment methods for solid malignancies are therefore needed. Mesenchymal stromal cells (MSCs) have been investigated for treatments for various types of solid tumor cancers due to their ability to target tumor cells with similar cell surface protein profiles. MSC-derived exosomes (MSC-Exos) elicit many of the tumor cell responses produced by MSC with no potential for differentiation and reduced risks of adverse effects. We surveyed the literature and clinical trials registries to identify studies investigating MSC-Exo-based anti-cancer therapies for gastric cancer, colorectal cancer, breast cancer, lung cancer, brain cancer, pancreatic cancer, and urological malignancies, and summarize the results of relevant studies herein to provide a comprehensive description of the therapeutic effects and potential clinical applications of MSC-Exos for the treatment of solid tumor malignancies. We include a summary of relevant clinical trials performed to date in an attempt to assess the data available regarding MSC-Exo safety, and propose future efforts regarding the requirements for transitioning forward from phase-1, 2 trials.