A growing body of evidence suggests a potential correlation between obesity and diabetic neuropathy (DN), but the causal nature of this relationship remains uncertain. We conducted a Mendelian randomization (MR) analysis to investigate the causal relationship between obesity and DN. Independent single nucleotide polymorphisms strongly associated with DN were identified from genome-wide association studies. Summary statistics for body mass index (BMI), waist circumference (WC), hip circumference (HC), and waist-to-hip ratio (WHR) were also obtained from genome-wide association studies datasets. The causal effects were estimated using inverse-variance weighted analysis, MR-Egger regression, and weighted median estimation. Sensitivity analyzes were performed to assess the robustness of the findings. Inverse-variance weighted analysis revealed significant negative associations of BMI (P = .0006, OR = 0.809, 95% CI: 0.716-0.913), WC (P = .008, OR = 0.792, 95% CI: 0.665-0.943), and HC (P = .032, OR = 0.871, 95% CI: 0.768-0.988) with DN risk. No significant association was observed for WHR (P = .425, OR = 0.954, 95% CI: 0.849-1.071). After Bonferroni correction (α = 0.0125), there was a statistically significant relationship between BMI and DN (P ≤ .0125), indicating a causal relationship. However, the causal relationships between WC, HC, WHR, and DN were not statistically significant, with P-values all > .0125. However, the OR value of MR analysis is close to 1, indicating that BMI may have a slight protective effect on the risk of DN.

IntroductionStroke survivors frequently present with varying degrees of sensory, cognitive, language, and motor impairments. Traditional Chinese exercises have been widely used as adjunctive rehabilitation therapies because they combine low-to-moderate intensity physical training, balance practice, proprioceptive stimulation, motor relearning, respiratory regulation, and cognitive engagement. However, intervention protocols and outcome measures vary substantially across trials, and direct head-to-head comparisons among Tai Chi, Baduanjin, Wuqinxi, Yijinjing, and standard of care remain scarce. This network meta-analysis therefore compared the relative effectiveness of different traditional Chinese exercise modalities for improving post-stroke motor outcomes.MethodsWe systematically searched Embase, Web of Science, Cochrane Library, PubMed, CNKI, VIP, and Wanfang Data from database inception to January 2026 for RCTs evaluating traditional Chinese exercises for post-stroke motor dysfunction. Eligible participants were adults with clinically diagnosed ischemic or hemorrhagic stroke in the acute, subacute, or chronic stage. The primary outcomes were upper- and lower-extremity motor function assessed using the FMA-UE and FMA-LE. Secondary outcomes were balance function assessed using the BBS and activities of daily living assessed using the BI. Risk of bias was assessed using the revised Cochrane risk-of-bias tool for randomized trials (RoB 2). A Bayesian network meta-analysis was performed, and intervention rankings were estimated using the SUCRA.ResultsFifty RCTs involving 3,718 participants were included. Compared with standard of care, Tai Chi and Wuqinxi showed statistically significant improvements in FMA-UE scores, whereas Baduanjin, Tai Chi, and Wuqinxi improved FMA-LE scores. All four exercise modalities were associated with significant improvements in BBS and BI scores. Ranking results suggested that Tai Chi had the highest probability of improving FMA-UE, Wuqinxi ranked highest for FMA-LE, Yijinjing ranked highest for BBS, and Baduanjin ranked highest for BI.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/view/CRD420261323853, CRD420261323853.

Type 2 diabetes (T2D) impairs antiviral immunity; however, the causal link between T2D and interferon-α2 (IFN-α2) deficiency remains unclear. This study used genome-wide association study-based Mendelian randomization (MR) to investigate this relationship and validated the findings in an H1N1-infected diabetic mouse model. MR analysis of 26 single nucleotide polymorphisms showed a significant negative association between T2D and IFN-α2 levels (inverse variance weighted odds ratio 0.667; P = 0.000116) without heterogeneity or pleiotropy. In vivo experiments confirmed that db/db mice exhibited more severe H1N1-induced lung injury, higher viral loads, and lower survival rates compared with nondiabetic controls. However, exogenous IFN-α2 treatment significantly reversed these pathologic outcomes. Inflammatory cytokine profiling showed that IFN-α2 downregulated 21 elevated cytokines and restored Fas ligand levels in lung tissue. Mechanistically, Western blotting demonstrated that IFN-α2 inhibited the phosphorylation of JAK1/2 and STAT3, thereby suppressing excessive inflammation. In conclusion, our findings indicate that T2D leads to IFN-α2 deficiency, contributing to susceptibility to viral infection. Supplementation with IFN-α2 effectively attenuated virus-induced lung injury by inhibiting JAK/STAT3 signaling and cytokine storms, positioning IFN-α2 supplementation as a promising therapeutic strategy for managing influenza complications in patients with diabetes. ARTICLE HIGHLIGHTS:Type 2 diabetes (T2D) is linked to impaired antiviral immunity, but whether it drives interferon-α2 (IFN-α2) deficiency remains unknown. We asked whether T2D causally suppresses IFN-α2 levels and whether exogenous supplementation could rescue host defense mechanisms against influenza infection. By integrating genetic analysis with an H1N1-infected diabetic mouse model, we show that T2D genetically lowers IFN-α2 and that treatment reverses lung injury by inhibiting JAK/STAT3-mediated hyperinflammation. Our study positions IFN-α2 supplementation as a promising therapeutic strategy to prevent severe viral pneumonia in patients with T2D.

BACKGROUND:In recent years, a considerable body of research has increasingly underscored the critical roles that protein Post-Translational Modifications (PTMs) play in the pathogenesis of Alzheimer's Disease (AD). However, a comprehensive bibliometric analysis of this field is still lacking. This study aims to systematically map research trends and hotspots and to identify promising directions for future work. METHODS:The data in this study were extracted from the Web of Science Core Collection (WOSCC) and visualized using CiteSpace, VOSviewer, R-bibliometrix, and Microsoft Excel 2016 to analyze bibliometric indicators including countries, institutions, authors, journals, citations, production categories, and keywords. RESULTS:A collection of 1,170 articles was retrieved, spanning the publication period from January 1, 1990, to December 31, 2024. The top three countries in terms of publications were the United States, China, and Germany. The most productive institution was the University of California System in the United States, contributing 57 articles. The leading authors identified were Mitkevich Vladimir, Perry George, and Makarov Alexander A. The Journal of Alzheimer's Disease was the top-ranked journal in terms of published papers. The most frequently cited article was "The NLRP3 Inflammasome: An Overview of Mechanisms of Activation and Regulation," published in the International Journal of Molecular Sciences. Finally, the most prolific research category was neuroscience, with 432 papers published. High-frequency keywords included Alzheimer's disease, phosphorylation, tau, and neurodegeneration. DISCUSSION:The study's findings suggest that PTM research in AD continues to revolve around the core pathological hallmarks represented by Aβ and tau protein. At the same time, some studies have reported aberrant modifications of α-synuclein and its potential role in AD. By systematically cataloging diverse PTM types and the molecular mechanisms involving Aβ and tau throughout AD progression, this analysis paves the way for a reassessment of AD pathogenesis from a "modification-function-pathology" perspective and provides a basis for identifying potential PTM-related targets and intervention strategies. CONCLUSION:This bibliometric analysis highlights the growing scholarly attention devoted to the relationship between PTMs and AD. The significant contributions and emerging trends emphasize the pivotal role of PTMs in the pathogenesis of AD, which may guide future biomarker discovery.

To observe the clinical effect and safety of Jiedu Yizhi Formula (JYF) in Alzheimer’s disease (AD) patients. Eligible patients with mild to moderate AD and Chinese medicine (CM) syndrome of Pi (Spleen)-Shen (Kidney) deficiency with phlegm-turbidity obscuring orifices were collected from the Third Affiliated Hospital of Changchun University of Chinese Medicine between December 2022 and December 2023. Patients were randomly assigned to JYF and donepezil groups at a 1:1 ratio by using a random number table and received a total of 24 weeks of continuous treatment. Both groups were given AD cognitive behavior training and health education at the same time. The Mini Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), AD Assessment Scale-Cognitive (ADAS-cog), Activity of Daily Living (ADL), and Hamilton Depression (HAMD) scale scores were measured before treatment, 12 and 24 weeks after treatment. The cognitive domain scores and the total effective rates were also compared between groups. During the study period, any adverse reactions were recorded and compared between groups. Totally 62 participants completed the study, with 31 in each group. The MMSE, MoCA, ADAS-cog, ADL, and HAMD scores significantly improved after 12 and 24 weeks of treatment in both groups (P<0.05 or P<0.01). Moreover, significant improvements in the ADL and HAMD scores were observed in the JYF group at 12 or 24 weeks than in the donepezil group (P<0.05 or P<0.01). Meanwhile, the cognitive domain scores of orientational and abstraction abilities and the total effective rate (64.52

Dyslipidemia contributes to chronic diseases such as non-alcoholic fatty liver disease (NAFLD), type 2 diabetes (T2DM), and obesity. Emerging evidence highlights gut dysbiosis as a key driver of abnormal lipid metabolism. This review examines how natural bioactive compounds from medicinal and food homology (MFH) substances regulate lipid metabolism by modulating the gut microbiome. It summarizes evidence on the modification of the microbiota-lipid metabolism axis by natural compounds from MFH substances and discusses the limitations of applications and their promise for preventing and treating metabolic diseases. By capitalizing on these microbiota-mediated effects, natural compounds may serve as a beneficial natural resource for adjusting lipid metabolism.

OBJECTIVES:Investigate Naochuxue formula's mechanism in the treatment of subarachnoid hemorrhage. METHODS:Analyzed Naochuxue formula's active components via nontargeted metabolomics, and predicted the core targets using network pharmacology. Sprague‒Dawley rats were randomly divided into six groups: sham, model, Naochuxue formula low, medium and high dose groups, and edaravone. Neurological deficits were assessed using the modified Garcia score and tissue damage was assessed by measuring the brain water content. Blood‒brain barrier permeability was assessed using the Evans blue procedure and pathological changes in the lesion site were observed through HE staining and Nissl staining. TUNEL staining and Caspase-3 immunofluorescence were used to observe the apoptosis of neurons in the hippocampus. The distribution and expression of p-PI3K and p-AKT were determined using immunohistochemistry. The expression of the apoptosis-related genes Caspase-3, Bcl-2, and Bax was determined using RT‒PCR. KEY FINDINGS:Compared with the model group, rats in the high-dose Naochuxue formula group exhibited significant improvements in neurological defects, brain histopathology, blood‒brain barrier permeability and brain edema on Day 3 posttreatment, downregulated Bax and Caspase-3 expression, and significantly upregulated p-PI3K, p-AKT, and Bcl-2 expression (all P < 0.05). CONCLUSIONS:High-dose formula for 3 days activated PI3K/AKT signaling pathway, inhibitd neuronal apoptosis, and exerted neuroprotective effects.

Staphylococcus aureus (S. aureus) is a highly pathogenic bacterium capable of causing a range of infections in humans and animals, from minor skin lesions to severe systemic diseases. The widespread use of antibiotics has exacerbated the issue of antibiotic resistance, notably with the emergence of methicillin-resistant Staphylococcus aureus (MRSA), complicating treatment strategies. This study investigated the potential of the natural compound puerarin to inhibit key virulence factors of S. aureus, specifically coagulase (Coa) and von Willebrand factor-binding protein (vWbp). Our results demonstrate that puerarin effectively inhibits Coa- and vWbp-induced coagulation without affecting bacterial growth. Cytotoxicity, invasion, and live/dead cell staining assays further revealed the excellent biocompatibility of puerarin and its ability to significantly reduce S. aureus-mediated cellular invasion and cytotoxicity. Scanning electron microscopy of in vitro catheter models revealed a marked reduction in bacterial adherence following puerarin treatment. Fluorescence quenching, western blot, and thermal shift assays (TSAs) revealed that puerarin does not alter the expression of Coa or vWbp but interacts directly with these proteins, impairing their stability and activity. Molecular docking and site-directed mutagenesis analyses identified critical residues in Coa and vWbp essential for puerarin binding, which was confirmed through in vitro coagulation assays. In a murine skin infection model, puerarin treatment ameliorated S. aureus-induced tissue damage and accelerated wound healing. Collectively, these findings highlight the therapeutic potential of puerarin as a novel antivirulence agent against S. aureus, offering a promising strategy to mitigate bacterial infections while addressing the challenge of antibiotic resistance.

Alzheimer's disease (AD) represents a neurodegenerative condition characterized by steadily increasing prevalence and incidence, arising significant challenge to both patients and social insurance. However, the etiology of AD remains controversial so far, and pathogenesis is far more complicated. Presently, no definitive therapeutic methodologies were available for AD, and only partial symptomatic relief can be achieved. Consequently, early diagnosis and intervention are emergently needed for AD patients. The diagnostic criteria for AD are continuously evolving, and biomarker testing is becoming increasingly critical for diagnosis. Currently, the diagnosis of AD primarily relies on the detection of pathological proteins through cerebrospinal fluid (CSF) testing and positron emission tomography (PET). However, factors such as high costs, operational contraindications, and invasiveness limited the application of these technologies, making them particularly challenging to implement in large-scale clinical trials and screenings. Core fluid biomarkers for AD including β-amyloid (Aβ), phosphorylated tau protein (p-tau), total tau protein (t-tau), and their combinations were found in CSF. Although these biomarkers were demonstrated with significant specificity and sensitivity, challenges remain high concerning the collection of CSF. Blood-derived biomarkers for Aβ and tau proteins are essential for preliminary screening, diagnosis, and monitoring of AD. Additionally, other bodily fluids such as saliva, urine, and tears have been investigated for their potential as biomarkers, offering unique characteristics and applications. Emerging biomarkers, including neurofilament light chain (NfL), neurogranin (Ng), Beta-site APP cleaving enzyme 1 (BACE1), synaptosome associated protein 25 (SNAP-25), as well as inflammation-related and gene-related factors, provided valuable insights into the diagnosis and pathogenesis of AD from diverse perspectives. Despite the substantial progress made in AD biomarker research, there are still baskets of limitations concerning the complication of the disease. The current review focused on the reported literature to summarize the biomarkers associated with AD. By critically analyzing studies published over the past decade, we aimed to strengthen the recent research progress, theoretical frameworks, and unresolved challenges related to AD biomarkers.

Diabetic cognitive impairment (DCI) is a form of cognitive dysfunction that affects individuals with diabetes, marking it as one of the complications linked to this disease. This condition typically presents as deficits in various cognitive abilities, such as memory, learning, language, motor skills, perception, and attention. Studies show that around 13% of diabetic individuals aged 65 to 74 experience cognitive impairment, with this figure rising to 24% for those over 75. As the global incidence of DCI increases, the economic and caregiving challenges for both individuals and society are also growing. The specific mechanisms underlying DCI remain unclear, and the relationships among various pathological processes are still under investigation. The study of DCI mechanisms continues to present numerous unresolved mysteries, such as unclear causal relationships: does metabolic disorder (e.g., hyperglycemia) directly damage neurons, or does it indirectly affect cognition through vascular lesions? Additionally, the mechanisms of individual heterogeneity pose further questions: why do some diabetic patients experience cognitive decline (CD) while others do not? Therefore, understanding the pathological alterations and the fundamental reason behind DCI is essential for improving early prevention and treatment strategies for individuals exhibiting clinical symptoms of this disorder. Furthermore, DCI represents a significant intersection between metabolic and neurodegenerative diseases, which encourages the integration of cognitive assessments into routine diabetes management. This article not only provides a systematic review of existing research but also serves as a bridge connecting basic science with clinical practice, offering theoretical support for the precise prevention and early diagnosis of DCI in patients.

Alzheimer's disease (AD) is a common neurodegenerative disorder with a complex pathogenesis. Oxidative stress, neuroinflammation and apoptosis play key roles in the occurrence and development of AD. The Nrf2/HO-1 signaling pathway, as an important endogenous antioxidant stress pathway in cells, is of great significance in combating oxidative damage and neurodegeneration. In recent years, an increasing number of studies have shown that traditional Chinese medicine can exert therapeutic effects on AD by regulating the Nrf2/HO-1 signaling pathway. This article aims to review the research progress of traditional Chinese medicine in regulating the Nrf2/HO-1 signaling pathway for the treatment of AD, providing new ideas and strategies for the treatment of AD.

Aim of the study：We studied the metabolites in the brain tissue of Alzheimer's Disease (AD) transgenic mice to investigate how Jiedu Yizhi Formula (JDYZF) protects against AD and to validate the scientific basis of the prescription using the "Marrow deficiency and toxin damage" theory. Materials and methods: The effect of JDYZF treatment on cognitive dysfunction was evaluated using the Morris water maze test in the APP/PS1 transgenic mouse model. Furthermore, the impact of JDYZF on typical AD pathology was assessed through Hematoxylin-eosin staining. Additionally, the protective effect of JDYZF on AD neurons was studied using Nissl staining. Moreover, potential mechanisms of action were analyzed through LC-MS/MS-based untargeted metabolomics of mouse brain tissue. Results: The administration of JDYZF significantly ameliorated memory deficits and mitigated typical histopathological changes in AD mice. Upon comparison of the differential metabolites between the model control group and the blank control group with those between the JDYZF group and the model control group, 17 endogenous metabolites, including 1-methyluric acid, were found to be significantly different. These differential metabolites were primarily involved in the pathways of caffeine metabolism and glycerophospholipid metabolism. Conclusion: In this study, we have effectively illustrated the neuroprotective effect of JDYZF on AD through experimentation with the APP/PS1 transgenic mouse model. The findings indicate that the utilization of JDYZF can ameliorate the metabolic disruptions in brain tissue and serve as a viable therapeutic intervention for AD.

Imbalance of inflammatory response and oxidative stress in bone microenvironment are the two most important mechanisms leading to the development and progression of osteoporosis. Developing high efficiency and low toxicity nanodrugs to regulate bone microenvironment has been emerging as potential strategy for therapy of human osteoporosis. Herein, functional icariin (ICA)-loaded selenium-Au multi-shell nanocomposites (SAS-ICA NPs) were designed. Under near-infrared light (NIR) irradiation, Au NPs showed a significant photothermal effect to trigger Se NPs and icariin releases, which synergistically inhibited the release of inflammatory factors and accumulation of reactive oxygen species (ROS). The results showed that SAS-ICA did not cause significant cytotoxicity towards macrophage and osteoblast. SAS-ICA treatment in vitro effectively induced macrophage phenotypic polarization, and inhibited release of inflammatory factors and ROS in macrophages. Additionally, SAS-ICA treatment in vitro significantly promoted alkaline phosphatase activation and the deposition of calcium nodules in osteoblast, implying the activation of osteoblasts. Importantly, SAS-ICA administration in vivo effectively improved bone mineral density (BMD) in ovariectomy mice by up-regulating type 1 colaggen (Col-1), Nuclear transcription-related factor 2 (Runx-2), bone formation protein (BMP2) and osteocalcin (OCN) expression and inhibiting osteoclast activation (TRAP staining). Moreover, SAS-ICA in vivo showed no side effects and good biocompatibility. Taken together, our findings validated the rational design that icariin-loaded selenium-Au multi-shell nanocomposites possessed NIR-II responsive release for synergetic theray of osteoporosis by regulating the bone microenvironment.

ObjectiveCurrently, traditional Chinese medicine (TCM) and its combinations are widely used in the treatment and rehabilitation of patients with ischemic stroke. However, current studies should mainly focus on the therapeutic effects of traditional Chinese medicines alone. This paper will employ a network meta-analysis to compare the efficacy of different TCM decoctions in the treatment of patients with ischemic stroke.MethodsChinese and English databases including PubMed, Embase, Cochrane Library, and Web of Science were searched to collect randomized controlled trials of TCM decoctions in the treatment of patients with ischemic stroke (IS), with a search time frame until April 2024. A library of references was created using EndNote 21. Quality assessment was performed using the Version 2 of the Cochrane risk-of-bias tool for randomized trials (RoB 2). A Bayesian network meta-analysis of data was performed using R4.3.1 and STATA 15.0.ResultsA network meta-analysis was conducted on 119 randomized controlled trials including 12,137 IS patients. The following TCM decoctions were involved: Xinglou Chengqi Decoction (XLCQT), Shenqi Tongluo Decoction (SQTLF), Zhongfeng Jiuxian Decoction (ZFJXT), Yiqi Tongluo Decoction (YQTLT), Tongqiao Huoxue Tang (TQHXT), Tongluo Xifeng Decoction (TLXFT), Tongluo Fuzheng Decoction (TLFZT), Xuefu Zhuyu Decoction (XFZYT), Xiaoxuming Decoction (XXMT), Qufeng Xingxue Tongluo Formula (QFXXTLF), Banxia Baizhu Tianma Decoction (BXBZTMT), Buyang Huanwu Tang (BYHWT),Huatan Tongluo Decoction (HTTLT), Yiqi Huoxue Tongluo Decoction (YQHXTLT), Yiqi Huoxue Decoction (YQHXT), and Yiqi Huoxue Kaiqiao Prescription (YQHXKQP). Of them, XFZYT was most effective in reducing the NIHSS score; SQTLF was most effective in increasing the Barthel Index (BI) score; and HTTLT was most effective in improving activities of daily living (ADL).ConclusionThis network meta-analysis provided data on the relative efficacy of different TCM decoctions. Of them, XFZYT was most effective in reducing the NIHSS score; SQTLF was most effective in increasing the BI score; and HTTLT was most effective in improving the ADL score. At the same time, overall, XFZYT ranked first with its best efficacy regarding all the three outcome measures above, and SQTLF came second with its impact on two of the outcome measures.

Alzheimer's disease (AD) is the most common neurodegenerative disease and is characterized by progressive cognitive decline. Pathologically, this disease is associated with the accumulation of extracellular amyloid plaques, intracellular neurofibrillary tangles (NFTs), and neuroinflammation. Current drug treatments primarily focus on managing symptoms rather than stopping disease progression. Disease-modifying therapies target the clearance of amyloid plaques through active and passive immunity methods. Although successful in animal models, human trials have shown adverse effects, such as meningoencephalitis, in a small number of patients who received active immunity methods. The efficacy of active immunity methods in treating AD remains uncertain, but passive immunity methods amyloid-beta (Abeta)-specific monoclonal antibody therapies such as aducanumab and lecanemab have been approved by the FDA. Despite the limitations of immune-based therapies, T-cell, and chimeric antigen receptor-based treatments show promise, but new guidelines are necessary to address potential adverse events. Research into the relationship between adaptive immune responses and AD is expected to provide innovative treatment approaches.

Alzheimer's disease (AD) is a fatal neurodegenerative disease characterized by its insidious onset and progressive development, making it the most common form of dementia. Despite its prevalence, the exact causes and mechanisms responsible for AD remain unclear. Recent studies have highlighted that inflammation in the central nervous system (CNS) plays a crucial role in both the initiation and progression of AD. Neuroinflammation, an immune response within the CNS triggered by glial cells in response to various stimuli, such as nerve injury, infection, toxins, or autoimmune reactions, has emerged as a significant factor alongside amyloid deposition and neurofibrillary tangles (NFTs) commonly associated with AD. This article aims to provide an overview of the most recent research regarding the involvement of neuroinflammation in AD, with a particular focus on elucidating the specific mechanisms involving microglia and astrocytes. By exploring these intricate processes, a new theoretical framework can be established to further probe the impact of neuroinflammation on the development and progression of AD. Through a deeper understanding of these underlying mechanisms, potential targets for therapeutic interventions and novel treatment strategies can be identified in the ongoing battle against AD.

Some studies have shown an association between dyslipidemia and diabetic neuropathy (DN), but the genetic association has not been clarified. Therefore, the present study aimed to investigate the genetic causal association between dyslipidemia and DN through a Mendelian randomization (MR) approach. Genetic causal associations between total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL), and high-density lipoprotein cholesterol (HDL) and DN were investigated by MR to provide a basis for the prevention and treatment of DN. Significant and independent single-nucleotide polymorphisms (SNPs) identified in genome-wide association studies were selected as instrumental variables (IVs) for MR analysis. Inverse variance weighted (IVW), MR‒Egger regression, weighted median (WME), simple mode (SM), and weighted mode (WM) methods were used to analyze causal associations. Heterogeneity and multiplicity tests were also performed and analyzed using the leave-one-out method to assess the stability of the results. Genetically predicted TC and DN (OR = 0.793, 95

Objective. This study aimed to investigate the mechanism of action of Jiedu Yizhi formula (JDYZF) in the treatment of Alzheimer’s disease (AD) through network pharmacology, molecular docking technology, and in vivo experiments. Method. The main active ingredients of seven herbs in the Chinese Medicine compound JDYZF were identified by searching the TCMSP database, PubChem database, CNKI, and other sources. Disease targets of AD were obtained from databases such as OMIM, TDD, DisGeNET, and DrugBank. A protein‒protein interaction (PPI) network was constructed using the STRING platform, and core targets were identified through topological analysis using Cytoscape software. Gene Ontology (GO) functional analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the relevant targets were performed using the Metascape database. The main active ingredients of JDYZF and potential core targets were identified based on degree values. Molecular docking technology was used to verify the interactions between the main active ingredients and potential core targets. Furthermore, water maze tests and hematoxylin-eosin (HE) staining of brain and liver tissues were performed to evaluate the effects of JDYZF on cognitive dysfunction in AD mice and neuronal damage in hippocampal brain tissue and to assess drug toxicity. PCR was performed to determine the expression levels of the apoptosis-related genes Bcl-2, Bax, and caspase-3 and to investigate the effect of JDYZF on hippocampal apoptosis in AD mice. Results. One hundred twelve core PPI target proteins, including CASP3, TP53, and VEGFA, were found between JDYZF and AD. The KEGG pathway enrichment analysis showed significant enrichment of the MAPK signaling pathway, PI3K/AKT signaling pathway and so on. Water maze tests revealed that the high-dose JDYZF treatment significantly improved the escape latency of AD model mice. The HE staining results showed that JDYZF exerted a protective effect on neuronal damage in the hippocampus of AD mice. JDYZF could upregulate the expression of the anti-apoptotic factor Bcl-2 while downregulating the expression of the proapoptotic factors Bax and caspase-3. Conclusion. JDYZF can improve the cognitive function of AD mice by suppressing cell apoptosis.

Alzheimer's disease (AD) is a fatal neurodegenerative disease with a subtle and progressive onset and is the most common type of dementia. However, its etiology and pathogenesis have not yet been fully elucidated. The common pathological manifestations of AD include extraneuronal β-amyloid deposition (Aβ), intraneuronal tau protein phosphorylation leading to the formation of 'neurofibrillary tangles' (NFTs), neuroinflammation, progressive loss of brain neurons/synapses, and glucose metabolism disorders. Current treatment approaches for AD primarily focus on the 'Aβ cascade hypothesis and abnormal aggregation of hyperphosphorylation of tau proteins', but have shown limited efficacy. Therefore, there is an ongoing need to identify more effective treatment targets for AD. The central nervous system (CNS) inflammatory response plays a key role in the occurrence and development of AD. Neuroinflammation is an immune response activated by glial cells in the CNS that usually occurs in response to stimuli such as nerve injury, infection and toxins or in response to autoimmunity. Neuroinflammation ranks as the third most prominent pathological feature in AD, following Aβ and NFTs. In recent years, the focus on the role of neuroinflammation and microglia in AD has increased due to the advancements in genome-wide association studies (GWAS) and sequencing technology. Furthermore, research has validated the pivotal role of microglia-mediated neuroinflammation in the progression of AD. Therefore, this article reviews the latest research progress on the role of neuroinflammation triggered by microglia in AD in recent years, aiming to provide a new theoretical basis for further exploring the role of neuroinflammation in the process of AD occurrence and development.