Abnormal glucose metabolism in the central nervous system is a major cause of sporadic Alzheimer's disease (SAD). We hypothesize that glycogen synthase kinase 3β (GSK3β) mediates cognitive impairment by inhibiting the Wnt/β-catenin pathway, which in turn induces abnormal glucose metabolism, synaptic damage, and mitochondrial dysfunction. To test this hypothesis, we injected streptozotocin bilaterally into the lateral ventricles of 100 male C57BL/6 J mice to establish in vivo models of SAD, and into HT22 cells to establish in vitro models of SAD. GSK3β expression was knocked down via adeno-associated virus (AAV) injection into the hippocampal CA1 region in vivo and via lentiviral transfection in vitro. We assessed cognitive function using the Morris water maze, Y-maze, and novel object recognition tests (n = 10). Glucose metabolism was evaluated by 18F-FDG PET imaging (n = 3), while synaptic and myelin sheath ultrastructure was examined using transmission electron microscopy (n = 6). Cell viability, mitochondrial function, and key protein expression were measured using CCK-8 assays, Seahorse analysis, and molecular biology techniques, respectively (n = 3, n = 6). In both in vivo and in vitro STZ-induced SAD models, GSK3β knockdown significantly reduced amyloid-β (1–42) deposition and tau hyperphosphorylation, activated the Wnt/β-catenin pathway, enhanced glucose metabolism, reversed glycolytic inhibition and mitochondrial dysfunction, and repaired synaptic and myelin sheath damage, ultimately improving cognitive deficits. Our findings demonstrate that GSK3β knockdown ameliorates STZ-induced SAD-like pathologies by restoring Wnt/β-catenin signaling and normalizing glucose metabolism, highlighting GSK3β as a potential therapeutic target for SAD.

This study aims to investigate the effects of Naotaifang(NTF) on neuronal ferroptosis and pyroptosis in cerebral ischemia-reperfusion injury(CIRI), with a focus on nuclear factor erythroid 2-related factor 2(Nrf2). A rat model of CIRI was established by middle cerebral artery occlusion/reperfusion(MCAO/R). Sprague-Dawley rats were randomly assigned to a sham group, a model group, low/medium/high-dose(4.5, 9, 18 g·kg~(-1), respectively) NTF groups, and a butylphthalide(60 mg·kg~(-1)) group(n=15 per group). After modeling, the treatment groups received corresponding agents by gavage once daily for 7 days, and the sham and model groups received an equal volume of normal saline. After treatment, the neurological function was assessed based on the Zea-Longa score, the infarct volume by TTC staining, and cellular morphology by HE staining. The levels of Fe~(2+), interleukin-1β(IL-1β), and interleukin-18(IL-18) were measured by ELISA, and those of malondialdehyde(MDA) and glutathione(GSH) by biochemical assays. Western blot was employed to examine the expression levels of Nrf2, glutathione peroxidase 4(GPX4), NOD-like receptor family pyrin domain-containing 3(NLRP3), and the N-terminal fragment of gasdermin D(GSDMD-N). In the cell experiment, oxygen-glucose deprivation/reperfusion(OGD/R) was used to model CIRI in SH-SY5Y cells. siRNA-mediated Nrf2 knockdown(si-Nrf2) was employed to probe into the role of Nrf2 in OGD/R-induced ferroptosis and pyroptosis and the intervention effect of NTF. Membrane damage was evaluated by Hoechst/propidium iodide staining and LDH release, and GPX4 and GSDMD immunofluorescence was employed to indicate ferroptosis and pyroptosis, respectively. Fe~(2+), MDA, and GSH were quantified biochemically, and the levels of IL-1β and IL-18 by ELISA. The expression of Nrf2, GPX4, NLRP3, and GSDMD-N was quantified by Western blot. The cellular ultrastructure was observed by transmission electron microscopy. The results of the animal experiment showed that NTF promoted the expression of Nrf2 to alleviate neuronal ferroptosis and pyroptosis, thus producing significant neuroprotection against CIRI in a dose-dependent manner. The results of the cell experiment showed that the neuroprotective effects of NTF after CIRI were mediated by Nrf2-dependent suppression of neuronal ferroptosis and pyroptosis. Taken together, NTF attenuates CIRI by suppressing neuronal ferroptosis and pyroptosis through Nrf2-mediated regulation.

Ischemia-reperfusion injury, a critical pathophysiological phenomenon in multiple organ systems, remains a formidable therapeutic challenge in clinical practice. As the third endogenously produced gaseous signaling molecule, hydrogen sulfide (H2S) has emerged as a pivotal regulator of diverse physiological processes and pathological cascades. Accumulating evidence indicates that H2S exerts cytoprotective effects against cerebral, cardiac, hepatic, renal, and pulmonary ischemia-reperfusion injuries through multifaceted mechanisms involving mitigation of inflammatory responses, suppression of oxidative stress, modulation of autophagic processes, and inhibition of apoptotic pathways. This comprehensive review systematically examines the endogenous biosynthesis and metabolic regulation of H2S, while elucidating the molecular mechanisms underlying its organ protective effects during ischemia-reperfusion injury. Particular emphasis is placed on the therapeutic potential of H2S synthase isoforms and bioactive metabolites in ischemic pathophysiology. Notably, recent advances in H2S pharmacology have catalyzed the development of novel H2S donors and slow-releasing compounds, including HSDF-NH2, S-allyl cysteine, S-propargyl cysteine, and S-(4-fluorobenzyl)-N-(3,4,5-trimethoxybenzoyl)-L-cysteine. These pharmacological innovations demonstrate enhanced tissue specificity and controlled release kinetics, paving the way for clinical translation of H2S-based therapeutics in ischemia-reperfusion injury management. Future research directions should focus on optimizing drug delivery systems and elucidating the spatiotemporal dynamics of H2S signaling in organ-specific ischemia-reperfusion pathologies.

Mitochondrial dysfunction, culminating in oxidative stress-driven release of mitochondrial DNA (mtDNA) and subsequent inflammatory activation, constitutes a central pathogenic axis in cerebral ischemia-reperfusion injury. Disrupting this axis requires precise antioxidant delivery to neuronal mitochondria, a major therapeutic hurdle. Here, we uncover that the natural flavonoid quercetin (Quer) possesses an intrinsic ability to bind mitochondrial outer membrane proteins, revealing its unexploited potential as a natural mitochondrial-targeting ligand. Leveraging this discovery, we engineered an ultrasmall mitochondria-targeting cascade nanozyme through coordination-driven self-assembly of the natural flavonoid Quer with Fe3+. MCN currently generates Fe2+/Fe3+ dual-valence centers that confer potent, superoxide dismutase-catalase cascade catalytic enzyme activities. We further confirmed that the MCN traverse the compromised blood-brain barrier, localize within the ischemic brain, and are selectively delivered to neuronal mitochondria in a rodent stroke model. Through its cascade elimination of key ROS, MCN stabilizes mitochondrial function and prevents mtDNA leakage. By blocking the released mtDNA from activating the cGAS-STING pathway in microglia, MCN reprograms the neuroinflammatory microenvironment and robustly attenuates brain injury, leading to significant functional recovery. This work establishes a paradigm of transforming inherent bioactivity of natural products into targeted catalytic nanomedicines, offering a precise therapeutic strategy for mitochondrial-centric diseases.

Ischemia-hypoxia-induced inflammation and glycolysis are linked to the severity of cerebral ischemia-reperfusion injury (CIRI), but the mechanisms are unclear. Current research suggests that the inflammatory response of immune cells activated by STING is a key regulatory molecule in cellular inflammatory damage. However, the specific mechanisms underlying STING-mediated CIRI inflammatory responses remain unclear. This study found that STING expression was specifically elevated in microglia in the damaged side of the hippocampus in CIRI model mice, and this elevation was positively correlated with the severity of CIRI. Our previous research indicated that the dynamic process of mitochondrial fusion and fission is closely associated with CIRI. Building on this, we integrated glycolysis, mitochondrial fission, and the STING inflammatory pathway. Mechanistically, our data suggest that DRP1 K616 is a critical candidate site involved in DRP1 lactylation-associated regulation, which promotes STING pathway activation and contributes to the progression of CIRI. In conclusion, our findings offer substantial evidence that lactate-driven DRP1-mediated mitochondrial fission facilitates the involvement of the STING inflammatory pathway in CIRI. These results suggest that modulating lactate metabolism may serve as a crucial upstream strategy for therapeutic intervention in CIRI.

Cerebral Small Vessel Disease (CSVD) is a dynamic whole-brain disease, characterized by pathological cascades that affect the brain's venules, capillaries, small arteries, and arterioles. Neuroimaging features of CSVD typically comprise Recent Small Subcortical Infarcts (RSSI), lacunes of presumed vascular origin, White Matter Hyperintensities (WMH) of presumed vascular origin, enlarged Perivascular Spaces (PVS), Cerebral Microbleeds (CMB), and Brain Atrophy (BA). The main clinical features of CSVD often include stroke, abnormal gait, psychiatric disorders, cognitive decline, and urinary incontinence, imposing a heavy burden on individuals and society. Despite its impact, the pathogenesis of CSVD remains unclear, and current clinical diagnosis relies primarily on neuroimaging, presenting considerable challenges for effective treatment. In recent years, most studies have addressed the pathophysiological and molecular mechanisms of CSVD, including chronic cerebral hypoperfusion, inflammatory cascades, oxidative stress, endothelial dysfunction, and Blood-Brain Barrier (BBB) leakage. In addition, genetic factors have been strongly associated with CSVD, though genetic heterogeneity and the complexity of internal environment homeostasis contribute to the persistent uncertainty surrounding its exact mechanisms. A comprehensive overview of these individual mechanisms is crucial for a holistic understanding of the pathogenesis of CSVD. Currently, there is a relative lack of therapeutic drugs and interventions for the complex pathogenesis of CSVD. The existing treatments, such as antihypertensives, antiplatelet agents, lipid-lowering drugs, and hypoglycemic agents, along with traditional alternative therapies like Chinese herbal medicine and acupuncture, have demonstrated efficacy in modulating the occurrence and progression of CSVD. These therapies provide a new perspective for developing more rational CSVD prevention strategies and treatment plans. This review systematically summarizes the cutting-edge research achievements in the field of pathological and physiological mechanisms of CSVD over the past few years, as well as potential treatment pathways and limitations, to provide a theoretical basis and intervention directions for the diagnosis and treatment of this patient population.

Osteosarcoma (OS) progression is critically influenced by the stromal microenvironment, yet we face a lack of reliable biomarkers. This study integrated single-cell and transcriptomic analyses to decipher stromal cell networks and identify novel diagnostic markers and therapeutic targets for OS. Using scRNA-Seq data and transcriptomic datasets obtained from the Gene Expression Omnibus (GEO), clustering analysis and communication analysis were performed with Seurat and CellChat packages, respectively. High-dimensional WGCNA (hdWGCNA) was applied to stromal cells to identify key gene modules. Hub genes from these modules were intersected with differentially expressed genes (DEGs) from DESeq2 analysis to pinpoint potential biomarkers. Their regulatory networks were predicted using the hTFtarget and ENCORI databases. Potential targeted drugs were screened via the DSigDB database and validated by molecular docking. Finally, functional assays were conducted using OS cell lines. Single-cell transcriptomics analysis identified seven major cell subpopulations (macrophages, stromal cells, T cells, plasma cells, endothelial cells, plasmacytoid dendritic cells, and mast cells). Cell communication analysis showed that stromal cells and macrophages can interact via CD99–CD99. hdWGCNA analysis clustered 19 gene modules in stromal cells, among which modules M14, M15, and M17 were closely associated with OS and enriched in pathways, such as ossification, extracellular matrix organization, and skeletal system development. Two potential biomarkers (CDKN2A and MMP14) were screened. Transcription factor (TF) and miRNA regulatory network predictions indicated that both the two potential biomarkers were situated in a complex post-transcriptional regulatory network. Drug prediction and molecular docking results revealed that MMP14 can stably bind to resveratrol. The proliferation, invasion, and migration capabilities of MMP14-silenced OS cell lines were significantly downregulated. This study identified CDKN2A and MMP14 as potential OS biomarkers and elucidated their role within the stromal cell network, suggesting resveratrol as a candidate therapeutic molecule targeting MMP14. The present discoveries provided new insights for understanding the progression mechanisms and developing precise diagnosis and treatment strategies for OS.

Alzheimer’s disease (AD) is a common neurodegenerative disorder; however, its molecular complexity remains poorly understood. Single-cell analysis can reveal the molecular changes in AD in different types of brain cells. In this study, we integrated single-cell sequencing and transcriptome data to explore the molecular mechanism of integrated stress response (ISR) in AD. Analysis of the GSE264648 (49 cases) and GSE48350 (253 cases) datasets showed that the integrated stress response (ISR) activity of endothelial cells in patients with AD was significantly increased compared with normal control group. Six key genes (BTG1, EPB41L4A, HERPUD1, SLC3A2, SLC7A11, and SLC7A5) were screened by combining the Least Absolute Shrinkage and Selection Operator (LASSO) regression and the random forest algorithm. Urine test for β-amyloid protein, Clinical Dementia Rating, modified Hachinski Ischemia Scale, Hamilton Depression Scale, Hamilton Anxiety Scale and head magnetic resonance imaging were used to screen cilinical subjects, and then verified the six key genes in their blood samples. These key genes are enriched in inflammatory pathways such as NF-κB and TNF, and are closely related to immune cell infiltration (e.g., M2 macrophages and neutrophils). This research also revealed the association between key and core genes of AD (e.g., APOE) and their clinical predictive value, providing new clues for mechanistic research and targeted therapy of AD.

Ischemic stroke (IS) is a major cause of mortality and disability, with thrombo-inflammation constituting a core pathophysiological mechanism. This process is closely linked to coagulation cascade activation, endothelial injury, immune cell infiltration, and neuronal damage. Coagulation factor XII (FXII), a key mediator of the contact activation pathway, has emerged as a promising therapeutic target due to its dual role in pathological thrombosis and immune regulation, without compromising physiological hemostasis. However, the clinical translation of FXII-targeted therapies is hindered by paradoxical observations. Recent studies highlight that FXII's functional complexity stems from its structural and spatial heterogeneity: full-length FXII derived from the liver and short FXII mRNA isoforms expressed in neurons mediate distinct biological effects. While FXII contributes to neuroinflammation and vascular injury via endothelial-platelet-neutrophil interactions, neuron-derived FXII exhibits neuroprotective effects through HGF-mediated signaling pathways. Additionally, circulating FXIIa promotes vascular remodeling by enhancing endothelial growth factor (VEGF) release. This review summarizes the multifaceted regulatory mechanisms of FXII in IS, focusing on its structure, distribution, preclinical-clinical paradox, and current therapeutic strategies. Special emphasis is placed on its domain-specific functions and the neuroprotective effects of FXII.

Blood heat syndrome,one of the main subtypes of blood syndrome in traditional Chinese medicine(TCM),is mainly diagnosed by bleeding and heat manifestations and treated by the blood-cooling method.The biological essence of blood heat syndrome has not been elucidated yet,and there is a lack of systematic research on the potential mechanisms underlying the blood-cooling method.The biological essence of blood heat syndrome is closely related to abnormal immune response,oxidative stress,coagulation dysfunction,endocrine disorders,abnormalities in energy metabolism and so on.Blood heat syndrome is common in autoimmune skin diseases(such as systemic lupus erythematosus,psoriasis,and purpura),central hyperthermia,infectious diseases(such as infectious mononucleosis and COVID-19),and hemorrhagic diseases in gynecology.As the primary clinical therapy for blood heat syndrome,blood-cooling TCM is usually combined with the TCM with effects of activating blood and resolving stasis,nourishing Yin,and extinguishing wind to play the role of cooling blood.The mechanisms of above therapies may be attributed to reducing inflammation,inhibiting oxidative stress,restoring the balance of blood coagulation and metabolism,regulating the secretion of sex hormones,and alleviating allergic reactions.This article systematically explores the biological essence of blood heat syndrome and elucidates the targets and underlying mechanism of the blood-cooling method,laying a scientific foundation for the clinical application of TCM in the prevention and treatment of diseases associated with blood heat syndrome.

INTRODUCTION:Knee osteoarthritis (KOA) is a common degenerative joint disease characterized by cartilage degradation, inflammation, and pain. Traditional Chinese Medicine, including JDJM (a herbal formula derived from the renowned Du Huo Ji Sheng Tang), has been used to alleviate symptoms of KOA, but its underlying mechanisms remain unclear. OBJECTIVE:This study aims to elucidate the potential therapeutic mechanisms of JDJM in treating KOA through network pharmacology, weighted gene co-expression network analysis (WGCNA), molecular docking, and experimental validation in animal models. METHODS:The active compounds of JDJM were identified through TCMSP database searches, and their potential targets were predicted using network pharmacology. WGCNA was employed to identify key modules and hub genes associated with KOA. Molecular docking was performed to assess the binding affinities of key compounds to critical inflammatory targets. Molecular dynamics (MD) simulations were used to evaluate the stability of the protein-ligand complexes. An experimental KOA model in rabbits was used to validate the therapeutic effects of JDJM. Histopathological examinations and inflammatory marker analyses were conducted to confirm the findings. RESULTS:Network pharmacology and WGCNA analyses identified 21 key targets and pathways potentially involved in the therapeutic effects of JDJM. Molecular docking results showed that Glyasperin C had the highest docking scores with EGF and IL-1β, followed by Stigmasterol with IL-6, Myricanone with INS, and Sesamin with VEGFA. MD simulations confirmed the stability of these protein-ligand complexes, indicating strong and stable interactions. In the rabbit KOA model, JDJM treatment significantly improved knee joint morphology and reduced the levels of inflammatory markers, such as IL-6 and TNF-α. Histopathological analysis revealed reduced cartilage degradation and inflammation in the JDJM-treated group compared to controls. CONCLUSION:JDJM exhibits promising anti-inflammatory and cartilage-protective effects, making it a potential therapeutic option for KOA patients. Further experimental and clinical studies are warranted to confirm these findings and translate them into clinical practice.

This meta-analysis aimed to evaluate the safety and efficacy of combining tirofiban with oral antiplatelet agents in treating patients with progressive ischemic stroke. The investigators searched several databases, including PubMed, Web of Science, the Cochrane Library, CNKI, VIP, WanFang Data and Sinomed. The search was restricted to literature published before May 5, 2025, without any language restrictions. Stata software 17.0 was used to analyze the results and assess risk of bias. A total of 19 studies comprising 3,667 patients were included in the analysis. Furthermore, statistically significant differences (P<0.05) were observed when comparing the tirofiban group and the control group regarding the incidence of achieving a 3-month modified Rankin scale (mRS) score of 0-2, the National Institutes of Health Stroke Scale score, the mRS score, activities of daily living, the platelet aggregation rate, the platelet adhesion rate and the effective rate. However, no significant differences (P>0.05) were detected in the risks of intracranial hemorrhage, other systemic hemorrhage, mortality rate and serious adverse events between the two groups. The study was conducted according to the preferred reporting items for systematic reviews and meta-analyses guidelines and registered with PROSPERO (no. CRD42025633357), and the findings suggested that tirofiban-augmented antiplatelet regimens safely improve clinical outcomes in progressive cerebral infarction, particularly when combined with dual oral antiplatelet agents.

Central nervous system (CNS) diseases, a leading cause of global disability and mortality, encompass a wide range of brain disorders such as stroke, Alzheimer's disease, Parkinson's disease, and so on. These diseases are characterized by dynamic cellular heterogeneity and disrupted intercellular crosstalk, yet their molecular drivers remain incompletely resolved. Single-cell RNA sequencing (scRNA-seq) dissects transcriptional diversity at cellular resolution, while spatial transcriptomics (ST) maps niche-specific interactions within tissue architecture-complementary approaches that have revealed disease-associated subpopulations, neural-glial communication, and microenvironmental remodeling. However, standalone omics layers inadequately capture the genetic, epigenetic, and functional cascades underlying CNS pathologies. Here, we highlight the transformative potential of integrating scRNA-seq and ST with multiomic profiling to delineate spatially orchestrated molecular networks. Such multiomic convergence enables systematic deconstruction of molecular mechanisms and intercellular communication across disease progression. By correlating these signatures with clinical phenotypes, this strategy accelerates biomarker discovery, patient stratification, and therapeutic target identification. We further discuss challenges in data harmonization, subcellular spatial resolution, and computational scalability that must be addressed to realize personalized CNS medicine. This synthesis advocates for interdisciplinary frameworks to translate multiomic insights into mechanistically grounded diagnostics and therapies, ultimately bridging the gap between molecular discovery and precision clinical intervention.

PANoptosis is a novelly defined mode of programmed cell death that involves the activation of multiple cellular death pathways, including pyroptosis, apoptosis, and necroptosis, triggering robust inflammatory reactions. Autophagy is a crucial cellular process that maintains cellular homeostasis and protects cells from various stresses. PANoptosis and autophagy, both vital players in the intricate pathological progression of ischemic stroke (IS), a brain ailment governed by intricate cell death cascades, have garnered attention in recent years for their potential interplay. While mounting evidence hints at a crosstalk between these two processes in IS, the underlying mechanisms remain elusive. Therefore, this review delves into and dissects the intricate mechanisms that underpin the intersection of PANoptosis and autophagy in this devastating condition. In conclusion, the crosstalk between PANoptosis and autophagy in IS presents a promising target for the development of novel stroke therapies. Understanding the interplay between these two pathways offers a much-needed insight into the underlying mechanisms of IS and opens the possibility for new therapeutic strategies.

Stroke is one of the most common causes of morbidity and mortality among adults globally. Significant advancements have been made in elucidating its pathophysiology, with stroke categorized into pathological subtypes, such as ischemic stroke (IS) and hemorrhagic stroke. White matter lesions (WMLs) identified on magnetic resonance imaging rank as a hallmark of cerebral small vessel disease and are associated with vascular risk factors. They are linked to adverse outcomes like dementia, depression, and an increased risk of both first-ever and recurrent strokes, independent of other risk factors. Despite the evidence indicating the close link between WMLs and stroke, their underlying pathophysiological relationship remains unclear. This study aims to provide an overview of the current knowledge and recent advances in epidemiology, risk factors, and pathophysiological mechanisms of WMLs and stroke, focusing on their interconnection and emerging therapeutic targets.

Cerebral ischemia-reperfusion injury (CIRI) has emerged as a hindrance for rehabilitation of ischemic stroke patients. Naotaifang (NTF) exhibits beneficial efficacy in alleviating inflammation and ferroptosis in vitro during CIRI. While the potential role of NTF in regulating mitochondrial dynamics in CIRI are not elucidated. This study aimed to explore the mechanism of NTF against CIRI by regulating the dynamin-related protein 1 (Drp1)-dependent mitochondrial fission/fusion. Modeling middle cerebral artery occlusion/reperfusion (MCAO/R) in vivo to evaluate the effects of NTF on the MCAO/R-damaged neurons and the structure, dynamics and function of mitochondria. An oxygen-glucose deprivation/reperfusion (OGD/R) cell model was established to evaluate the role of NTF in OGD/R-damaged cells. Function of Drp1 in CIRI and the neuroprotection of NTF through the mitochondrial fission/fusion pathway were investigated in vivo and in vitro. The results revealed that in vivo, NTF alleviated neuron injury in a dose-dependent manner, down-regulated Drp1 and fission protein 1 (Fis1) levels, upregulated optic atrophy 1 (Opa1), mitofusin 1/2 (Mfn1 and Mfn2), facilitated mitochondrial fusion and inhibited mitochondrial fission to rescue cells from CIRI. In vitro, Drp1 overexpression inhibited mitochondrial fusion and activated mitochondrial fission, while silencing of Drp1 exhibited the opposite result. NTF rebalanced mitochondrial dynamic in the OGD/R cell model. NTF could alleviate neuron injury following CIRI by regulating the balance of mitochondrial fission and fusion. Targeting Drp1-dependent mitochondrial dynamics may represent a viable treatment strategy for addressing the issues of CIRI post ischemic stroke.

The ion channel protein PIEZO1 regulates complex processes in Alzheimer’s disease (AD). This study explored the regulatory mechanism of PIEZO1 in AD using bioinformatic analysis, aiming to identify AD-associated genes and potential therapeutic strategies. RNA sequencing (RNA-seq) data based on an in vitro model of AD were obtained from the Gene Expression Omnibus (GEO) database, and differential expression analysis was performed using the DESeq2 R package. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted on the identified differentially expressed genes (DEGs). Gene set enrichment analysis (GSEA) and principal component analysis (PCA) were also performed on the gene expression data. PCA clustering revealed overall significant differences among the three groups of samples (control, AD, and PF-562271 intervention group). All DEGs in the three sample groups were subjected to k-means hierarchical clustering, revealing four clusters. The matrix antigen plot indicated multiple changes in the average millions of fragments per thousand bases value of each gene among the groups. Functional annotation was performed for the DEGs between the two groups, and GSEA identified both activated and inhibited pathways, distinguishing the groups. Notably, the expression of PIEZO1 was higher in the AD group than in the control group. This study confirmed elevated PIEZO1 expression in astrocyte AD models, which is associated with the regulation of the extracellular matrix, cell–substrate adhesion, synaptic migration, and other related functions and pathways.

Network Meta-analysis was conducted to evaluate the efficacy and safety of different traditional Chinese medicine injections combined with conventional western medicine in treatment of cerebral small vessel disease(CSVD). Computerized searches were conducted in PubMed, Cochrane Library, Web of Science, EMbase, CNKI, Wanfang, VIP, and SinoMed for randomized controlled trial(RCT) published in Chinese or English using traditional Chinese medicine injections to treat CSVD. The search time is from the inception to July 15, 2024. Literature screening and statistical analysis were conducted with NoteExpress 3.0.3, RevMan 5.3.5, and Stata 15.1.6. A total of 45 articles were included, involving 3 717 patients, with 1 944 patients in the treatment group and 1 773 patients in the control group. A total of 15 kinds of traditional Chinese medicine injections were involved. Network Meta-analysis indicated that,(1) in terms of improving clinical total effective rate, the best intervention in SUCRA was Ciwujia Injection + conventional western medicine.(2) In terms of reducing NIHSS scores, the best intervention in SUCRA was Xueshuantong Injection + conventional western medicine.(3) In terms of improving ADL scores, the best intervention in SUCRA was Danshen Injection + conventional western medicine.(4) In terms of improving MMSE scores, the best intervention in SUCRA was Xueshauntong Injection + conventional western medicine.(5) In terms of improving MoCA scores, the best intervention in SUCRA was Salvianolate Injection + conventional western medicine.(6) In terms of reducing plasma viscosity(PV), the best intervention in SUCRA was Danhong Injection + conventional western medicine.(7) In terms of reducing the hematocrit, the best intervention in SUCRA was Xuesaitong Injection + conventional western medicine.(8) In terms of reducing fibrinogen, the best intervention in SUCRA was Xuesaitong Injection + conventional western medicine.(9) In terms of reducing erythrocyte sedimentation rate(ESR), the best intervention in SUCRA was Danshen Injection + conventional western medicine.(10) In terms of reducing total cholesterol(TC), triglycerides(TG), and low-density lipoprotein(LDL), the best intervention in SUCRA was Danshen Injection + conventional western medicine. The radar chart results indicated that the advantage of Salvianolate Injection lies in improving cognitive function, while the advantage of Xueshuantong Injection lies in improving neurological function. The advantage of Xuesaitong Injection lies in improving hemodynamic parameters, and the advantage of Danshen Injection lies in improving behavioral ability, hemodynamics, and blood lipid levels. In terms of safety, there was no significant difference in the incidence of adverse reactions between the traditional Chinese medicine injection treatment group and the conventional western medicine group, and no serious adverse reactions occurred. The results showed that the combination of traditional Chinese medicine injections and conventional western medicine can effectively improve the clinical total effective rate, the neurological and cognitive functions, hemodynamic parameters, and blood lipid levels of patients suffering from CSVD. In addition, more double-blind, multi-center, large-sample RCT is needed to verify these findings and to provide more high-quality evidence on the efficacy and safety of traditional Chinese medicine injections for CSVD.