Neuroinflammation is a key driver and an important therapeutic target of neurodegeneration. Dysregulated nuclear factor-κB (NF-κB) signaling plays a central role in neuroinflammation and depends on M1 and K63 ubiquitination of NF-κB essential modulator (NEMO). Ivangustin (IVA) is a sesquiterpene lactone isolated from Inula japonica Thunb., a traditional Chinese medicine has been used to treat inflammatory diseases. But its anti-neuroinflammatory effects and molecular targets remain unclear. This study aimed to evaluate the anti-neuroinflammatory effects of IVA and elucidate its direct functional target and underlying mechanism. Integrated in vitro, in vivo, and in silico/bioinformatics approaches were employed. The anti-neuroinflammatory activity of IVA was evaluated in LPS-stimulated BV2 cells, primary microglia, and an LPS-induced acute cognitive impairment mouse model. Mechanistic studies were performed using pull-down, liquid chromatography-tandem mass spectrometry (LC–MS/MS), cellular thermal shift assay (CETSA), drug affinity responsive target stability (DARTS), gene knockdown, point mutation and bioinformatics analyses. In vitro, IVA significantly inhibited nitric oxide (NO) production and mRNA and protein expression of pro-inflammatory factors in LPS-stimulated microglia. Furthermore, IVA significantly suppressed inhibitor of NF-κB kinase α/β (IKKα/β) and inhibitory subunit of NF-κB alpha (IκBα) phosphorylation, IκBα degradation, and NF-κB p65 phosphorylation and nuclear translocation, thereby blocking the expression of NF-κB-targeted genes. Its anti-neuroinflammatory activity was attenuated by thiol donors, indicating the importance of its electrophilic lactone moiety. Furthermore, ubiquitin conjugating enzyme E2L3 (UBE2L3) was identified as the functional target of IVA in BV2 cells, whereas UBE2L3 knockdown markedly attenuated IVA-mediated anti-neuroinflammatory action. Bioinformatics analysis suggests UBE2L3 overexpression as a potential risk factor for neurodegenerative diseases. Mechanistically, IVA covalently bound to the catalytic cysteine 86 of UBE2L3, thereby inhibiting UBE2L3-mediated M1 and K63 ubiquitination of NEMO, which is crucial for NF-κB activation. In vivo, IVA ameliorated LPS-induced cognitive impairment and neuroinflammation in mice via inhibiting Iba1 expression and suppressing NF-κB activation. IVA exerts anti-neuroinflammatory effects by covalently targeting UBE2L3 and suppressing NF-κB signaling. These findings also identify UBE2L3 as a potential therapeutic target for neuroinflammation and support IVA as a promising lead compound for further preclinical investigation of neuroinflammatory disorders.

BackgroundIdiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease in which genetic susceptibility interacts with epithelial, immune, and mesenchymal remodeling. Although the chromosome 11p15.5 locus contains established IPF susceptibility signals near MUC5B and TOLLIP, the broader regulatory architecture of this region remains incompletely resolved.MethodsWe integrated IPF genome-wide association study summary statistics with methylation, expression, and protein quantitative trait loci using summary-data-based Mendelian randomization (SMR). SMR-prioritized candidates were evaluated in independent transcriptomic and methylation cohorts and further contextualized using microRNA, transcription-factor, protein-interaction, machine-learning, single-cell, and spatial transcriptomic analyses. Fibrosis-associated expression patterns were assessed in a bleomycin-induced pulmonary fibrosis rat model.ResultsThe analyses recovered the established MUC5B and TOLLIP signals and prioritized BRSK2 as a comparatively underexplored candidate supported by eQTL-based SMR and independent molecular evidence. The BRSK2 pQTL association did not pass the HEIDI test and was therefore not interpreted as convergent protein-level genetic evidence. Network analyses linked BRSK2 to cell-cycle, metabolic-stress, and senescence-related programs, while cross-cohort machine learning prioritized FOXA2, CDC25B, and NFE2 as informative network features. Single-cell and spatial analyses localized BRSK2 preferentially to fibroblast and myofibroblast compartments and to regions with greater histological fibrosis severity. In fibrotic rat lungs, BRSK2 expression increased, whereas FOXA2 and CDC25B decreased at the transcript and protein levels.ConclusionsThese findings refine the molecular landscape of the chromosome 11p15.5 IPF susceptibility locus and prioritize BRSK2 as a candidate component of an IPF-associated profibrotic fibroblast state. Its causal contribution, direct regulatory relationships, and therapeutic tractability require targeted mechanistic validation.

Skeletal muscle dysfunction (SMD) is a clinically important extrapulmonary manifestation of chronic obstructive pulmonary disease (COPD) and is associated with impaired exercise capacity, reduced physical function, increased exacerbation risk, and poorer clinical outcomes. Although traditionally viewed as a consequence of pulmonary disease progression, accumulating evidence suggests that pulmonary impairment and skeletal muscle abnormalities may reflect partially overlapping processes within the systemic pathobiology of COPD. This narrative review synthesizes clinical, imaging, genetic, mechanistic, and therapeutic evidence and uses the lung–muscle axis as a conceptual framework to organize established clinical relationships, shared systemic mechanisms, functional coupling, and candidate inter-organ signaling pathways. Available studies indicate that pulmonary abnormalities and SMD are associated and may share determinants including chronic inflammation, oxidative stress, mitochondrial dysfunction, metabolic dysregulation, cellular aging, and impaired tissue adaptation. Functional coupling among respiratory muscle performance, peripheral muscle capacity, and exercise tolerance further supports the clinical relevance of this framework. Circulating mediators, myokines, and extracellular vesicles have been proposed as potential mechanisms of inter-organ signaling; however, direct molecular communication and bidirectional causal effects remain incompletely established. These relationships vary according to disease phenotype, environmental exposure, disease stage, and host susceptibility. Clinically, the lung–muscle framework may broaden COPD phenotyping and management by complementing pulmonary assessment with measures of muscle function, physical performance, nutritional status, and imaging-derived muscle characteristics. Future longitudinal, multi-omics, and tissue-resolved studies are needed to clarify causal pathways, distinguish biologically relevant mediators from disease-associated biomarkers, and determine whether targeted interventions can preserve both respiratory and skeletal muscle function.

BACKGROUND:Cognitive impairment is a significant health concern among older adults, highlighting the need for non-pharmacological interventions, such as mind-body exercises. However, a comprehensive synthesis of the effects of various traditional Chinese exercises (TCEs) on cognitive function in older adults is lacking. METHODS:A systematic review and meta-analysis of randomised controlled trials (RCTs) was conducted. Six databases were searched from inception to 2 May 2024 for studies examining the effects of TCEs on cognitive outcomes in adults aged 60 years and older. Studies were included if they were RCTs involving TCEs and reported outcome measures for global cognition, or individual cognitive domains. RESULTS:Twenty-eight RCTs with a total of 2297 participants were included. Meta-analysis revealed that TCEs led to significant improvements in global cognition: Montreal Cognitive Assessment [mean differences (MD) = 1.67; 95% confidence interval (CI): (1.20, 2.14)], Mini-Mental State Examination [MD = 0.76; 95% CI: (0.04, 1.48)]; executive function: Trail Making Test (B-A) [MD = -7.96; 95% CI: (-15.34, -0.59)], Category Fluency for Animals [MD = 2.96, 95% CI (2.08, 3.85)]; working memory: Digit Span-Backwards [MD = 0.48; 95% CI: (0.07, 0.90)]; processing speed: Digit Symbol Coding [MD = 4.16; 95% CI: (1.82, 6.50)]; memory function: Memory Quotient [MD = 13.13; 95% CI: (4.06, 22.20)], Auditory Verbal Learning Test: immediate recall [MD = 1.13; 95% CI: (0.07, 2.20)], short-term delayed recognition [MD = 0.80; 95% CI: (0.28, 1.32)] and long-term delayed recognition [MD = 1.38; 95% CI: (0.68, 2.09)]. CONCLUSIONS:TCEs are effective in improving cognitive function in older adults, particularly in domains such as global cognition, executive function, working memory, processing speed and memory function. However, given the methodological limitations and heterogeneity of the included studies, these findings require confirmation in further large-scale, high-quality RCTs.

BackgroundThe triglyceride-glucose (TyG) index is an established surrogate marker of insulin resistance. However, most evidence has relied on a single baseline measurement and may not fully capture long-term metabolic exposure. This study examined whether longitudinal TyG trajectories are independently associated with subsequent incident type 2 diabetes mellitus (T2DM).MethodsThis retrospective longitudinal cohort study used repeated health examination data from adults without diabetes at baseline between 2011 and 2025. TyG trajectories were identified using latent class mixed models based on repeated TyG measurements. Follow-up for incident T2DM began after the third eligible TyG measurement to preserve temporal ordering between exposure assessment and outcome occurrence. Multivariable Cox proportional hazards models with multiple imputation were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Restricted cubic splines and time-dependent area under the curve (AUC) analyses were used for dose-response and predictive performance assessments.ResultsAmong 16, 751 participants included in trajectory modeling, three TyG trajectory groups were identified and ordered by mean TyG level: low-ascending (G1), moderate-ascending (G2), and high-persistent (G3). A total of 10, 163 participants contributed follow-up after the third-visit landmark, among whom 430 incident T2DM events were recorded. Incidence rates were 2.90, 13.47, and 37.25 per 1, 000 person-years in G1, G2, and G3, respectively. In the main adjusted model, compared with G1, both G2 (HR = 2.27, 95% CI: 1.64-3.14) and G3 (HR = 5.40, 95% CI: 3.87-7.53) were associated with higher risks of incident T2DM (both P < 0.001). A graded association was observed across trajectory levels (HR per level increase = 2.34, 95% CI: 2.01-2.72; P < 0.001). Adding TyG information provided modest incremental discrimination beyond the base clinical model, with limited additional improvement over baseline TyG alone.ConclusionsLongitudinal TyG trajectories identified distinct diabetes risk strata among adults undergoing repeated health examinations. A high-persistent TyG trajectory was associated with increased risk of incident T2DM after the landmark time point, supporting the potential value of monitoring TyG dynamics for early risk stratification in routine care.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder increasingly associated with peripheral inflammatory conditions such as chronic periodontitis (CP); however, the molecular mechanisms linking these conditions remain poorly understood. Here, we investigated the therapeutic effects of Huanglian Jieddu Decoction (HLJDD) on CP-induced AD using an integrative machine learning-guided multi-omics approach. Analysis of public single-cell RNA-sequencing data revealed pronounced inflammatory activation in microglia from AD samples. We further established a CP-induced AD rat model and performed hippocampal transcriptomic profiling. Multiple complementary machine learning strategies, including Random Forest-based feature selection, support vector machine-based refinement, network modeling, and interpretable model analysis, were applied to prioritize disease-relevant pathways from high-dimensional transcriptomic data. Across models, components of the cGAS-STING signaling pathway consistently exhibited strong and directional contributions to CP-AD pathology, indicating a central inflammatory axis linking peripheral infection to neurodegeneration. Guided by these data-driven insights, in vivo and in vitro experiments demonstrated that HLJDD suppressed cGAS-STING activation, attenuated neuroinflammation, and improved cognitive function in CP-induced AD models. Collectively, this study highlights the value of machine learning-assisted transcriptomic interpretation for mechanistic prioritization and identifies HLJDD as a multitarget therapeutic strategy for CP-induced AD.

Prediabetes is characterized by its high global prevalence and significant risk of progression to diabetes. The current research focus lies in precise risk stratification and intervention, wherein precision medicine plays a critical role by integrating multi-omics data with clinical information. This study examines how precision medicine concepts, including risk stratification, biomarker-guided subtyping, and individualized intervention, have progressively permeated prediabetes research, acknowledging that these ideas often integrate with, rather than replace, traditional prevention frameworks. Publications were retrieved from the Web of Science Core Collection (WoSCC). Visualization and quantitative analyses were conducted using CiteSpace 6.4.R1 and VOSviewer 1.6.20. A total of 103 publications were included, involving 607 authors from 347 institutions across 50 countries/regions. The USA led in publication volume and international collaboration, with Harvard Medical School and the University of Copenhagen emerging as the most influential institutions. Journals with high impact factors, such as The Lancet Diabetes and Endocrinology and The New England Journal of Medicine, accounted for a substantial share of citations in this corpus. Keyword co-occurrence and burst analyses revealed that research hotspots have shifted from metabolic risk factors such as hypertension and impaired glucose tolerance toward insulin resistance, genetic biomarkers, precision nutrition, and artificial intelligence–assisted patient stratification. Current research emphasizes individualized intervention strategies supported by multi-omics technologies, continuous glucose monitoring, and artificial intelligence. Future efforts should focus on integrating dynamic biomarkers and personalized nutrition into scalable precision prevention frameworks, offering new avenues for early diagnosis, timely treatment, and stratified interventions in prediabetes.

Huang-Lian-Jie-Du decoction (HLJDD), a typical formulation for heat clearance and detoxification, shows therapeutic potential for oral diseases and cognitive impairment. Nevertheless, the mechanism by which HLJDD influences periodontitis-induced cognitive impairment via the microbiota-gut-brain axis remains unknown. We investigated HLJDD’s neuroprotective effects in periodontitis rats, focusing on its modulation of the microbiota-gut-brain axis and underlying molecular mechanisms. Chemical profiling of HLJDD was performed via UHPLC-Q-Exactive Orbitrap HRMS. Periodontitis was induced in SD rats using ligatures and Porphyromonas gingivalis for 2 weeks, followed by 8-week treatments with HLJDD (0.75/1.5/3 g/kg/day), doxycycline (10 mg/kg/day), or vehicle. Alveolar bone loss was assessed via micro-CT, while cognitive function was assessed via the Morris water maze (MWM). Hippocampal and colon pathology was analyzed via H E, Nissl staining, and immunohistochemistry. The composition of gut microbiota was analyzed by 16S rDNA sequencing. The tight junction proteins in hippocampus and colon were examined by RT- qPCR and immunofluorescence (IF). Inflammatory cytokine levels in intestinal and hippocampus tissue and serum were quantified by ELISA. Network pharmacology predicted potential mechanisms, and Western blotting assessed TLR4/NF-κB pathway proteins. HLJDD contained 94 bioactive compounds and significantly attenuated alveolar bone loss, improved cognitive function, and reduced neuronal damage and Aβ deposition. It restored gut microbiota homeostasis, enhanced intestinal and blood–brain barrier integrity, and suppressed neuroinflammation by modulating pro- and anti-inflammatory cytokines. Mechanistically, HLJDD inhibited TLR4/NF-κB signaling, suggesting its therapeutic potential in periodontitis-related cognitive impairment. HLJDD ameliorates cognitive impairment in periodontitis by modulating the microbiota-gut-brain axis, reducing neuroinflammation, and inhibiting TLR4/NF-κB activation. These findings support its potential as a novel therapeutic strategy for periodontitis-associated cognitive impairment.

BACKGROUND:The intricate interrelationship between oral health, the number of teeth, oral microbiota, and frailty remains largely unexplored in clinical research. This study aimed to investigate the interrelationship between oral microbiome, the number of teeth, and frailty. METHODS:Data from 4518 participants in NHANES 2009-2012 were analyzed. Frailty was measured using the 48-item Frailty Index (FI). Multivariable logistic regression and restricted cubic spline (RCS) evaluated associations between alpha diversity and frailty. Mediation analysis was used to assess the role of number of teeth. The associations between oral microbiome diveristy and mortality were analyzed by Cox regression. Beta diversity was examined with PCoA and PERMANOVA. RESULTS:The prevalence of frailty was 39.73 %. Univariate analysis showed that alpha diversity indices except for the Simpson index were significantly lower in frailty, and after adjusted for confounders, observed ASVs (adjusted OR: 0.80 [0.73, 0.87], p < 0.001), Faith's PD (adjusted OR: 0.81 [0.74, 0.88], p < 0.001) and Shannon-Weiner index (adjusted OR: 0.88 [0.81, 0.95], p = 0.002) were remained significantly associated with frailty. The reduced number of teeth partially mediated the relationship (for Faith's PD: βindirect = -0.001 [-0.003, 0.000], p = 0.036, proportion: 8.33 % [0.00 %, 37.50 %]; for Shannon-Weiner index, βindirect = -0.007 [-0.013, -0.002], p = 0.007, Proportion = 17.07 % [3.39 %, 65.00 %]). Univariable Cox proportional hazard regression showed that all alpha diversity indices were significantly associated with all-cause mortality in frail population, and in multivariable analysis, Shannon-Weiner index (HR: 0.72 [0.55, 0.94], p = 0.017) and Simpson index (HR: 0.71 [0.60, 0.83], p < 0.001) remained statistically significant. PCoA showed that beta diversity was also significantly associated with frailty. CONCLUSION:Lower oral microbiome diversity is associated with higher frailty and mortality. The number of teeth partially mediates this link, emphasizing the importance of oral health in mitigating frailty and promoting healthy aging.

Background:Acute ischemic stroke (AIS) is a common cerebrovascular disease associated with insufficient brain perfusion and accumulation of waste materials, which may further impair the glymphatic system. We aimed to investigate glymphatic activity using the diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) method and assess its correlation with upper limb motor dysfunction in AIS patients, as well as identify factors associated with these changes. Methods:We prospectively enrolled 59 patients with AIS [mean age: 62.4; males: 40; mean symptoms onset to magnetic resonance imaging (MRI): 5.9 days] and 29 age- and sex-matched healthy controls (HCs), among whom 18 patients underwent a second MRI scan. The ALPS index was utilized to assess glymphatic function. We compared the ALPS index between AIS patients and the HCs group in both hemispheres. Additionally, we investigated the association between ALPS index on the side of infarction and clinical variables including time since stroke onset, infarct volume, Fugl-Meyer Assessment of the Upper Extremity (FMA-UE) scores, and National Institutes of Health Stroke Scale (NIHSS) scores. Furthermore, we examined changes in ALPS index from baseline to follow-up in 2 months. Results:Among 59 patients, 27 (45.8%) had left hemispheric infarct. The mean ALPS index on the ipsilateral side of the AIS patients was significantly lower than that on the contralateral side (1.225±0.132 vs. 1.337±0.138, P<0.001) and the corresponding side in the HCs group (P<0.001). Additionally, the mean ALPS index on the contralateral side of the infarct was significantly lower when compared to the corresponding side in the HC group (1.233±0.078 vs. 1.450±0.211 on the left side; 1.217±0.165 vs. 1.450±0.155 on the right side, both P<0.001). The ALPS index demonstrates a significant positive correlation (ρ=0.404, P=0.001) with FMA-UE and a notable negative correlation (ρ=-0.484, P<0.001) with the NIHSS score. However, subsequent MRI follow-up of the 18 patients revealed a statistically significant elevation in the ALPS index compared to baseline (1.296±0.141 vs. 1.174±0.109, P=0.001). Conclusions:Our findings suggest that a decreased ALPS index in AIS patients with upper limb motor dysfunction indicates impaired glymphatic function. Moreover, the level of the ALPS index is associated with the severity of stroke. ALPS index could be a potential neuroimaging biomarker for AIS patients with upper limb motor dysfunction.

Purpose:To investigate the predictive value of Traditional Chinese Medicine Constitution (TCMC) in cognitive frailty (CF) among older adults and explore its potential influencing pathways. Patients and Methods:From 2021 to 2023, a total of 905 older participants were recruited from three geographic regions in China: Southwest (Sichuan), East (Shanghai), and North (Beijing). A multidimensional survey (including TCMC assessment) was conducted. Prediction models were developed using nomogram and C5.0 decision tree algorithms. Internal and external validations were performed. The KHB method was applied for mediation analysis. Results:Logistic regression identified Qi-stagnation constitution (QSC) and Qi-deficiency constitution (QDC) as important risk factors for CF (P < 0.01). Both the C5.0 decision tree model and Nomogram model based on TCMC demonstrated strong predictive performance (AUC=0.824 and 0.812, respectively). External validation indicated superior extrapolability of the C5.0 model (AUC=0.810 vs 0.772). Mediation analysis revealed that sleep quality partially mediated the association between QSC and CF (P < 0.05), with a mediation proportion of 22.7%. Conclusion:QSC and QDC were identified as modifiable risk factors for CF. Prediction models based on TCMC demonstrated strong predictive performance and generalizability. Furthermore, QSC may worsen CF progression through its detrimental effects on sleep quality, identifying its clinical applicability as both a risk stratification factor and a prevention focus for CF.

Myocardial ischemia-reperfusion injury (MIRI) remains a major clinical challenge, with oxidative stress as a key driver. Despite extensive preclinical promise, antioxidant therapies have consistently failed in clinical translation. This critical review deconstructs this translational gap, which stems from the nuanced complexity of redox biology, inappropriate therapeutic timing, and patient heterogeneity. We argue that overcoming these hurdles requires a paradigm shift from broad antioxidant supplementation to precision medicine. This approach involves enhancing endogenous defense mechanisms, leveraging targeted drug delivery, and developing multi-modal strategies. Ultimately, integrating dynamic biomarkers, multi-omics, and artificial intelligence to tailor treatments to individual patient profiles holds the key to finally fulfilling the promise of effectively managing MIRI.

IntroductionHuang-Lian-Jie-Du Decoction (HLJDD), a botanical drug used in traditional medicine, has been used in the management of Alzheimer’s disease (AD). However, the mechanisms underlying its preventive effects remain inadequately understood, particularly due to the absence of metabolomic studies examining alterations in serum and cerebrospinal fluid (CSF) metabolites. Moreover, the potential toxicities and side effects of HLJDD necessitate further pharmacological investigation. This study aims to explore the differential effects of HLJDD on AD model rats and healthy controls through a metabolomics approach and uncover the underlying mechanisms based on changes in serum and CSF metabolites. The findings are expected to provide a scientific foundation for enhancing the clinical safety and rational use of HLJDD.MethodsThe composition of HLJDD was characterized by UPLC-Q-Exactive Orbitrap HRMS. Aβ1-42-induced SD rats served as the AD animal model. Rats in the sham + HLJDD and Aβ1-42 + HLJDD groups (0.604 g/kg freeze-dried powder) were treated with HLJDD via gavage for 28 days. Nissl staining was performed to assess hippocampal neuronal changes, while H&E staining was used to evaluate histopathological alterations in the brain, liver, kidneys, stomach, large intestine, and small intestine. Aβ expression was determined using IHC and ELISA, and inflammatory levels in both peripheral and central systems were quantified by ELISA. MMP-2 and MMP-9 expression were analyzed through IHC. LC-MS was employed to investigate metabolic variations in serum and CSF.ResultsHLJDD reduced Aβ deposition in Alzheimer’s disease rats, enhanced neuronal survival, reduced inflammation, preserved blood-brain barrier (BBB) integrity, and alleviated damage to the brain, kidneys, and stomach. These therapeutic effects were associated with the arginine biosynthesis pathway and ferroptosis. In contrast, HLJDD induced peripheral and central inflammation, impaired neuronal function, compromised BBB integrity, and caused damage to the liver, kidneys, and large intestine in normal rats. These adverse effects were linked to disruptions in aminobenzoate degradation and nucleotide metabolism.ConclusionHLJDD may alleviate Aβ-induced damage repair in Alzheimer’s disease rats, but it also induces varying degrees of toxicity in normal rats.

Purpose:To assess the practicality and utility of employing dual post-label delay (PLD) arterial spin labeling (ASL) in transient ischemic attack (TIA) individuals exhibiting Fluid-attenuated inversion recovery (FLAIR) vascular hyperintensity (FVH). Materials and methods:We conducted a retrospective review of clinical data from TIA patients presenting with unilateral severe atherosclerotic stenosis or obstruction of either the intracranial internal carotid artery or the middle cerebral artery. Participants were categorized into two groups based on the presence or absence of FVH: FVH positive and FVH negative. All individuals underwent pseudo-continuous ASL perfusion imaging, utilizing distinct PLD durations (1,525 and 2,525 ms) alongside qualitative visual assessments of ASL perfusion irregularities. Standardized TIA evaluations, which included medical history reviews, neuropsychological assessments, and ABCD2 scoring, were performed on all subjects. We explored the correlations between FVHs, clinical manifestations, vascular risk factors, and perfusion metrics. Results:A total of 50 patients were included in this investigation, with FVH detected in 16 subjects (32.0%). The ABCD2 score was notably elevated within the FVH positive cohort compared to the FVH negative group. At a PLD of 1,525 ms, cerebral blood flow (CBF) values for the affected and healthy hemispheres in the FVH positive group were recorded at 19.55 ± 6.67 and 40.32 ± 6.83, respectively; corresponding values in the FVH negative group were 23.74 ± 5.03 and 46.43 ± 7.91. For a PLD of 2,525 ms, the CBF values for the affected and healthy sides in the FVH positive group were 34.11 ± 5.87 and 50.27 ± 8.57, while the FVH negative group recorded values of 42.79 ± 7.03 and 52.07 ± 7.29, respectively. The differential CBF (ΔCBF) for the affected side in the FVH positive and negative groups was 14.57 ± 4.34 and 19.05 ± 6.10, respectively. A significant negative correlation was established between ΔCBF and ABCD2 scores (Kendall's tau-b = -0.578, p < 0.001). Conclusion:The findings of this study indicate a strong association between the presence of FVH signs and a marked reduction in cerebral blood flow, as well as diminished blood flow reserve. This underscores the potential role of FVH as a biomarker for hemodynamic impairment in TIA patients.

OBJECTIVE:With the increasing number of patients with cognitive impairment, nonpharmacological ways to delay cognitive impairment have attracted people's attention, such as lifestyle changes and nutritional supplementation. Folic acid supplementation appears to be a promising treatment option. However, it remains controversial whether folic acid supplementation is effective in delaying adult's cognitive impairment. Therefore, we conducted a meta-analysis to analyze the effects of folic acid supplementation on different cognitive impairments. METHODS:We systematically searched PubMed, Web of Science, EMbase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure (CNKI), WanFang and VIP databases for randomized controlled trials on January 22, 2024. The included population comprised those diagnosed with cognitive impairment. We included trials that compared folic acid treatment with placebo, other dosing regimens, or other intervention controls. Conducting quality evaluation of included studies according to the Cochrane Risk of Bias tool. Statistical analyses were performed using Review Manager software. RESULTS:Twenty-two trials, including 3604 participants, met inclusion criteria. Compared with controls, the cognitive function of Alzheimer's disease (AD) patients showed improvement with folic acid supplementation: supplementation with < 3 mg (standardized mean differences (SMD) = 0.15, 95% confidence interval (CI) -0.10 to 0.41), and supplementing with ≥ 3 mg folic acid could improve cognitive function in AD patients (SMD = 1.03, 95% CI 0.18 to 1.88). Additionally, it reduced homocysteine (HCY) levels (mean differences (MD) = -4.74, 95% CI -8.08 to -1.39). In mild cognitive impairment (MCI) patients, cognitive function improved with folic acid supplementation: supplementation with > 400 μg (SMD = 0.38, 95% CI 0.13 to 0.63), and supplementation with ≤ 400 μg (SMD = 1.10, 95% CI 0.88 to 1.31). It also reduced HCY levels at intervention ≤ 6 months (MD = -3.93, 95% CI -5.05 to -2.82) and intervention > 6 months (MD = -4.38, 95% CI -5.15 to -3.61). However, supplementing with folic acid did not improve cognitive function in vascular cognitive impairment (VCI) patients, with folic acid supplements < 3 mg (SMD = -0.07, 95% CI -0.23 to -0.08), folic acid supplements ≥ 3 mg (SMD = 0.46, 95% CI -0.57 to 1.49), however, it reduced HCY levels at intervention > 6 months (MD = -5.91, 95% CI -7.13 to -4.69) and intervention ≤ 6 months (MD = -11.15, 95% CI -12.35 to -9.95). CONCLUSIONS:Supplement folic acid is beneficial to the cognitive profile of patients with MCI, supplementation with ≥ 3 mg folic acid can improve cognitive function in AD patients.

Alzheimer’s disease is a common neurodegenerative condition that severely affects the quality of life of patients and their families, resulting in a substantial societal burden. In the pathogenesis of Alzheimer’s disease, the p38 mitogen-activated protein kinase pathway is closely associated with neuroinflammation, apoptosis, synaptic plasticity, amyloid beta deposition, and aberrant tau phosphorylation. Natural products have a high potential for therapeutic modulation of the P38 MAPK pathway. We searched PubMed, EMBASE, Medline, and Web of Science, utilizing the keywords “Alzheimer’s disease,” “neurodegenerative diseases,” “MAPK,” and “P38MAPK” and “natural products” to identify natural products that can be used to treat Alzheimer’s disease by modulating the P38MAPK pathway. Various natural products were found to act on p38 MAPK, including saponins, flavonoids, alkaloids, acids, terpenoids, and glycosides. All these active agents can treat Alzheimer’s disease through their interactions with p38 MAPK. This study aimed to examine the use of natural products to intervene in Alzheimer’s disease and regulate the p38 MAPK pathway to provide potential ideas for further drug research and development.

忍冬属植物作为金银花入药品种较多,现市场流通的有金银花、山银花以及川银花,均具清热解毒、发散风热之效,临床常混用,其用法用量并无区分,但研究显示三者化学成分及药理作用有一定差异.文章从知网、万方、百度文库等多个网站中查询近年文献报道,就金银花、山银花、川银花的资源分布、化学成分、药理作用进行整理、讨论,并进行对比分析,以期为金银花、山银花、川银花的研究开发和临床应用提供参考.

我国老年群体人口基数大、增长快、患病率高,且大多存在生理机能与心理调控能力下降的双重问题.目前我国慢病管理模式存在数据采集方式落后、数据管理与使用困难、诊疗过程耗费时间及医疗资源配置不均等问题.传统的慢病管理模式无法解决慢病患病人数与人民群众日益增长的医疗卫生健康需求之间的矛盾.完善我国的慢病管理模式,是公共卫生领域乃至全社会亟待解决的问题.智慧医疗是一种基于云计算、大数据分析的新型医疗模式,将其运用到传统慢病管理模式中能有效解决数据采集、管理及分析等问题.我国中医药文化底蕴深厚,群众基础广泛,中医健康干预对老年人心身健康具有良性调节作用.因此,立足国情,结合智慧医疗打造具有中国特色的老年慢病管理的中医服务模式,实现慢病数据采集方式创新、数据管理平台优化、慢病诊疗过程便捷以及医疗资源的合理配置,具有深远的社会意义与临床价值.

Background: Berberine has been widely used for the adjuvant therapy of several cardiovascular diseases (CVDs). However, evidence for its efficacy remains controversial. Purpose: This study aimed to evaluate the efficacy and safety of berberine in CVDs. Study design: A systematic review and meta-analysis of randomized controlled trials (RCTs). Methods: We searched ten electronic databases for articles from inception to December 23, 2022. RCTs comparing berberine alone or combined with statins versus statins or routine for CVDs were included. Meta-analysis was performed according to the Cochrane Handbook. Results: Forty-four RCTs were included with 4606 patients. There were no differences between berberine alone and routine or statins in improving total cholesterol (TC) (SMD, 0.43; 95% CI,-0.39 to 1.24; p = 0.30; I-2 = 95%), triglyceride (TG) (SMD,-0.14; 95% CI,-0.49 to 0.21; p = 0.44; I-2 = 76%), low-density lipoprotein cholesterol (LDL-C) (SMD, 0.69; 95% CI,-0.23 to 1.60; p = 0.14; I-2 = 96%), high-density lipoprotein cholesterol (HDL-C) (SMD, 0.55; 95% CI,-0.48 to 1.57; p = 0.30; I-2 = 96%), and Crouse score levels. Berberine alone significantly reduced National Institute of Health Stroke Scale (NIHSS) score, high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and intima-media thickness (IMT) levels than routine therapy. Berberine plus statins significantly reduced TC, TG, LDL-C, NIHSS score, hs-CRP, TNF-alpha, IMT, Crouse score, and number of unstable plaques levels than routine or statins. However, no differences were found be-tween groups in improving HDL-C and IL-6 levels. There were no significant differences between groups in the incidence of adverse reactions. Conclusion: This study suggests that berberine may be a promising alternative for CVDs with no serious adverse reactions. However, our results may be limited by the quality of existing research. High-quality RCTs are needed to provide more convinced evidence.

社区获得性肺炎(CAP)是临床多发的感染性疾病之一.近年来,广谱抗菌药物大量使用,CAP病原耐药谱趋于复杂,使CAP的诊疗日益困难.2016年中华医学会呼吸学分会感染学组发布《中国成人社区获得性肺炎诊断和治疗指南》(简称中国指南),2019年美国胸科学会(ATS)与美国感染病学会(IDSA)发布《2019 ATS&IDSA临床实践指南:成人社区获得性肺炎的诊断和治疗》(简称ATS&IDSA指南)用于规范临床诊疗.笔者综合中国指南和ATS&IDSA指南,重点探讨CAP抗感染治疗方案,将两者的差别和一致强调的内容进行比较,为临床诊疗提供参考.