ObjectiveTo develop a community-family management model for older adults with mild cognitive impairment (MCI) and to formulate detailed application specifications, and to fully leverage the initiative of communities and families under limited resource conditions, for achieving community-based early detection and early intervention for older adults with MCI. MethodsA systematic literature review was conducted to identify pertinent publications. Corpus-based research methodologies were employed to extract, refine, integrate and synthesize management elements, thereby establishing the specific content and service processes for each stage of the management model. Utilizing the 5W2H analytical framework, essential elements such as management stakeholders, target populations, content and methods for each stage were delineated. The model and its application guidelines were finalized through expert consultation and demonstration. ResultsAn expert evaluation of the management model yielded mean scores of 4.84, 4.32 and 4.84 for acceptability, feasibility and systematicity, respectively. By integrating the identified core elements with expert ratings and feedback, the final iteration of the community-family management model for older adults with MCI was formulated. This model comprised of five stages: screening and identification, comprehensive assessment, intervention planning, monitoring and referral pathways to ensure implementation, and enhanced support for communities, family members and caregivers. Additionally, it included 18 specific application guidelines. ConclusionThe proposed management model may theoretically help delay cognitive decline, improve cognitive function and potentially promote reversal from MCI to normal cognition. It may also enhance the awareness and coping capacity of older adults and their families, strengthen community healthcare professionals' ability to early identify and manage MCI.

ObjectiveNeuroinflammation plays a crucial role in both the onset and progression of ischemic stroke, exerting a significant impact on the recovery of the central nervous system. Excessive neuroinflammation can lead to secondary neuronal damage, further exacerbating brain injury and impairing functional recovery. As a result, effectively modulating and reducing neuroinflammation in the brain has become a key therapeutic strategy for improving outcomes in ischemic stroke patients. Among various approaches, targeting immune regulation to control inflammation has gained increasing attention. This study aims to investigate the role of in vitro induced regulatory T cells (Treg cells) in suppressing neuroinflammation after ischemic stroke, as well as their potential therapeutic effects. By exploring the mechanisms through which Tregs exert their immunomodulatory functions, this research is expected to provide new insights into stroke treatment strategies. MethodsNaive CD4⁺ T cells were isolated from mouse spleens using a negative selection method to ensure high purity, and then they were induced in vitro to differentiate into Treg cells by adding specific cytokines. The anti-inflammatory effects and therapeutic potential of Treg cells transplantation in a mouse model of ischemic stroke was evaluated. In the middle cerebral artery occlusion (MCAO) model, after Treg cells transplantation, their ability to successfully migrate to the infarcted brain region and their impact on neuroinflammation levels were examined. To further investigate the role of Treg cells in stroke recovery, the changes in cytokine expression and their effects on immune cell interactions was analyzed. Additionally, infarct size and behavioral scores were measured to assess the neuroprotective effects of Treg cells. By integrating multiple indicators, the comprehensive evaluation of potential benefits of Treg cells in the treatment of ischemic stroke was performed. ResultsTreg cells significantly regulated the expression levels of both pro-inflammatory and anti-inflammatory cytokines in vitro and in vivo, effectively balancing the immune response and suppressing excessive inflammation. Additionally, Treg cells inhibited the activation and activity of inflammatory cells, thereby reducing neuroinflammation. In the MCAO mouse model, Treg cells were observed to accumulate in the infarcted brain region, where they significantly reduced the infarct size, demonstrating their neuroprotective effects. Furthermore, Treg cell therapy notably improved behavioral scores, suggesting its role in promoting functional recovery, and increased the survival rate of ischemic stroke mice, highlighting its potential as a promising therapeutic strategy for stroke treatment. ConclusionIn vitro induced Treg cells can effectively suppress neuroinflammation caused by ischemic stroke, demonstrating promising clinical application potential. By regulating the balance between pro-inflammatory and anti-inflammatory cytokines, Treg cells can inhibit immune responses in the nervous system, thereby reducing neuronal damage. Additionally, they can modulate the immune microenvironment, suppress the activation of inflammatory cells, and promote tissue repair. The therapeutic effects of Treg cells also include enhancing post-stroke recovery, improving behavioral outcomes, and increasing the survival rate of ischemic stroke mice. With their ability to suppress neuroinflammation, Treg cell therapy provides a novel and effective strategy for the treatment of ischemic stroke, offering broad application prospects in clinical immunotherapy and regenerative medicine.

This study explored the potential therapeutic targets and mechanisms of Danggui Shaoyao San(DSS) in the prevention and treatment of Alzheimer's disease(AD) through transcriptomics and metabolomics, combined with animal experiments. Fifty male C57BL/6J mice, aged seven weeks, were randomly divided into the following five groups: control, model, positive drug, low-dose DSS, and high-dose DSS groups. After the intervention, the Morris water maze was used to assess learning and memory abilities of mice, and Nissl staining and hematoxylin-eosin(HE) staining were performed to observe pathological changes in the hippocampal tissue. Transcriptomics and metabolomics were employed to sequence brain tissue and identify differential metabolites, analyzing key genes and metabolites related to disease progression. Reverse transcription-quantitative polymerase chain reaction(RT-qPCR) was employed to validate the expression of key genes. The Morris water maze results indicated that DSS significantly improved learning and cognitive function in scopolamine(SCOP)-induced model mice, with the high-dose DSS group showing the best results. Pathological staining showed that DSS effectively reduced hippocampal neuronal damage, increased Nissl body numbers, and reduced nuclear pyknosis and neuronal loss. Transcriptomics identified seven key genes, including neurexin 1(Nrxn1) and sodium voltage-gated channel α subunit 1(Scn1a), and metabolomics revealed 113 differential metabolites, all of which were closely associated with synaptic function, oxidative stress, and metabolic regulation. RT-qPCR experiments confirmed that the expression of these seven key genes was consistent with the transcriptomics results. This study suggests that DSS significantly improves learning and memory in SCOP model mice and alleviates hippocampal neuronal pathological damage. The mechanisms likely involve the modulation of synaptic function, reduction of oxidative stress, and metabolic balance, with these seven key genes serving as important targets for DSS in the treatment of AD.
Animals ; Alzheimer Disease/genetics* ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Mice, Inbred C57BL ; Metabolomics ; Transcriptome/drug effects* ; Maze Learning/drug effects* ; Hippocampus/metabolism* ; Humans ; Disease Models, Animal ; Memory/drug effects*

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

The water-sediment interface is an important zone for the migration and transformation of chemical substances,but traditional sampling methods make in situ sampling challenging,thus it is difficult to capture information on environmental processes at the micro-scale.In this study,diffusive gradients in thin films(DGT)probe technique was used as in situ tool to detect 18 kinds of typical per-and polyfluoroalkyl substances(PFAS)in the water-sediment system,elucidating their vertical distribution characteristics and patterns.The results showed that different PFAS exhibited distinct variation patterns with depth in water and sediment.Short-chain PFAS exhibited greater mobility,while the migration of long-chain PFAS was restricted in sediment and pore water due to their strong hydrophobicity and adsorption capacity,resulting in relatively small concentration changes in the sediment column.The PFAS concentrations measured by DGT ranged from 11.2 μg/L to 1305 μg/L.For long-chain PFAS,the concentrations measured by DGT were higher than those obtained from direct measurement of water and pore water,while the opposite results were obtained for short-chain PFAS.The DGT results indicated that although long-chain PFAS exhibited strong adsorption to sediment particles,the adsorbed PFAS were still bioavailable.DGT probe technique,with its advantages of in situ sampling and high spatial resolution,provides deep insights into the complex environmental processes occurring at the microscale in the water-sediment systems.DGT offers important technical support and scientific evidence for assessing the adsorption-desorption behavior,bioavailability,and ecological risks of these emerging pollutants in aquatic environment.

Dementia in traditional Chinese medicine （TCM） mainly presents amnesia and dullness. Alzheimer's disease and vascular dementia belong to the category of dementia in TCM. These progressive neurological diseases have a complex etiology and a long course， and the drugs that can reverse the disease course remain to be developed. Therefore， early intervention plays a vital role in delaying the disease progression. Apathy refers to a lack of motivation that leads to the attenuation or disappearance of goal-directed behaviors， cognitive functions， and emotional responses. Clinical studies have suggested that apathy exists in the early stage of a variety of neurodegenerative diseases， being one of the key symptoms to the early diagnosis of dementia. The severity of apathy is related to the severity of dementia. Therefore， early diagnosis and treatment of apathy are of great significance to the prevention and treatment of dementia. The preclinical research on apathy in dementia is still in its infancy， and the systematic evaluation method has not been prescribed. The clinical diagnosis and treatment are also in the exploratory stage， and the complex pathophysiological mechanisms of apathy and dementia development have not been fully elucidated. This article reviews the research progress of apathy in dementia， the apathetic behaviors of dementia animal models， the behaviors of patients with apathy， and the treatment methods in recent years and summarizes the research status of apathy in dementia. This review aims to provide a theoretical basis for exploring the behavior of apathy in dementia and conducting preclinical research and evaluation of the pathogenesis and to lay a foundation for the treatment of apathy in dementia.

Traditional Chinese medicine （TCM） has a long history of application in China and has consistently played a vital role in treating diseases and saving lives. TCM prescriptions （compounds） constitute the primary form of clinical TCM treatment and significantly differ from western medicine （chemicals） due to the diverse composition and chemical constituents of TCM （compounds）. Nevertheless， the potential multi-component， multi-target， and multi-pathway action characteristics of TCM prescriptions also demonstrate their possible （complementary） therapeutic advantages when compared with single-component chemical drugs. Therefore， driven by the development of modern science and technology and the demands of the modernization and internationalization of TCM， modern theories regarding the complexity of TCM prescription effects have been continuously proposed： Different from the abstract language of traditional prescription theory， the modern TCM prescription theory is more inclined to illustrate the connotation of prescription compatibility concretely and vividly from an experimental and scientific perspective. In this paper， new theories on the complexity of TCM prescriptions proposed in recent years are summarized to provide research references and ideas for the greater role of TCM prescriptions and a better scientific understanding.

Demyelination of the central nervous system often occurs in neurodegenerative diseases， such as multiple sclerosis （MS）. The myelin sheath， a layer of myelin membrane wrapping the axon， plays a role in the rapid conduction and metabolic coupling of impulses for neurons. The exposure of the axon will lead to axonal degeneratio， and further neuronal degeneration， which is the main cause of dysfunction and even disability in patients with demyelinating neurodegenerative diseases. In addition to the demyelination of mature myelin sheath， remyelination disorder is also one of the major reasons leading to the development of the diseases. The myelin sheath is composed of oligodendrocytes （OLs） derived from oligodendrocyte progenitor cells （OPCs） which are differentiated from neural stem cells （NSCs）. The process of myelin regeneration， i.e.， remyelination， is the differentiation of NSCs into OLs. Recent studies have shown that this process is regulated by a variety of genes. MicroRNAs， as important regulators of neurodegenerative diseases， form a complex regulatory network in the process of myelin regeneration. This review summarizes the main molecular pathways of myelin regeneration and microRNAs involved in this process and classifies the mechanisms and targets. This review is expected to provide a theoretical reference for the future research on the treatment of demyelinating diseases by targeting the regulation of microRNAs.

Objective To explore the value of vesical imaging reporting and data system(VI-RADS)combined with absolute tumor-wall contact length(ABTCL)and actual tumor-wall contact length(ACTCL)in diagnosing muscle invasive bladder cancer(MIBC).Methods The MRI data of 113 patients with pathologically confirmed bladder cancer(BCa)were analyzed retrospectively.All patients underwent conventional MRI,diffusion weighted imaging(DWI)and dynamic contrast enhanced(DCE)MRI before sur-gery.Two radiologists independently evaluated MRI images based on VI-RADS score,and measured quantitative parameters,inclu-ding ABTCL and ACTCL.The Chi-square test was used to compare the difference of VI-RADS scores between MIBC and non-mus-cle invasive bladder cancer(NMIBC).Quantitative parameters between MIBC and NMIBC were compared by Mann-Whitney U test.The receiver operating characteristic(ROC)curve was used to evaluate the diagnostic value of VI-RADS,quantitative parameters and VI-RADS combined with quantitative parameters in the diagnosis of MIBC.Results VI-RADS,ABTCL and ACTCL had significant differences between MIBC and NMIBC(P＜0.05).The area under the curve(AUC)for VI-RADS,ABTCL and ACTCL in diagno-sing MIBC were 0.89,0.76 and 0.77,respectively.There was no significant difference between the AUC for ABTCL and ACTCL(P＞0.05).The AUC for VI-RADS combined with ABTCL or ACTCL in diagnosing MIBC was 0.93,higher than that of only VI-RADS(P＜0.05).Conclusion The combination of VI-RADS with either ABTCL or ACTCL can effectively improve the diagnostic performance of MIBC.ABTCL obtainedby linear measurement is easier to implement in clinical practice than ACTCL obtained by curved measurement.

AIM: To analyze and screen influencing factors of diabetic patients complicated with retinopathy, and establish and validate prediction model of nomogram.METHODS: A total of 1 252 patients from the Diabetes Complications Early Warning Dataset of the National Population Health Data Archive(PHDA)between January 2013 to January 2021 were selected and randomly divided into a modeling group(n=941)and a validation group(n=311). Univariate analysis, LASSO regression and Logistic regression analysis were used to screen out the influencing factors of diabetic retinopathy, and a nomogram prediction model was established. The receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve were used to evaluate the model. The clinical benefit was evaluated by the decision curve analysis(DCA).RESULTS: Age, hypertension, nephropathy, systolic blood pressure(SBP), glycated hemoglobin(HbA1c), high-density lipoprotein cholesterol(HDL-C), and blood urea(BU)were the influencing factors of diabetic retinopathy. The area under the curve(AUC)of the modeling group was 0.792(95%CI: 0.763-0.821), and the AUC of the validation group was 0.769(95%CI: 0.716-0.822). The Hosmer-Lemeshow goodness of fit test and calibration curve suggested that the theoretical value of the model was in good agreement(modeling group: χ2=14.520, P=0.069; validation group: χ2=14.400, P=0.072). The DCA results showed that the threshold probabilities range was 0.09-0.89 for modeling group and 0.07-0.84 for the validation group, which suggested the clinical net benefit was higher.CONCLUSION: This study constructed a risk prediction model including age, hypertension, nephropathy, SBP, HbA1c, HDL-C, and BU. The model has a high discrimination and consistency, and can be used to predict the risk of diabetic retinopathy in patients with diabetes.