Influenza- and COVID-19-associated pulmonary aspergillosis (IAPA and CAPA respectively) are associated with increased mortality in critically ill patients. We evaluated whether longitudinal bronchoalveolar lavage (BAL) galactomannan (GM) dynamics predict clinical outcomes in these patients.

In a retrospective cohort (2009-2024) at a tertiary care ICU in Belgium, 180 adult patients with probable/proven IAPA (n = 68) or CAPA (n = 112) requiring mechanical ventilation were included. A total of 698 BAL samples were analysed. GM optical density values were modelled using linear mixed-effects models (10- and 30-day follow-up windows), with outcome measures at 30 and 90 days. Bayesian joint models linked longitudinal GM trends with time-to-death, adjusting for age, Charlson Comorbidity Index (CCI) and immunosuppression. Associations between Aspergillus culture results dynamics and mortality were also assessed.

In general, BAL GM values declined significantly over days after diagnosis of aspergillosis, with steeper reductions in survivors (interaction p < 0.05). Joint models revealed each unit increase in GM over time corresponded to a 19% higher hazard of death at both 30 (aHR 1.19, p = 0.02) and 90 days (aHR 1.19, p = 0.007) after ICU admission. Persistent BAL culture positivity also correlated with worse outcomes.

In this large virus-associated pulmonary aspergillosis cohort, BAL GM kinetics emerged as a potential prognostic biomarker. Early and sustained increases in BAL GM values identify patients at increased risk of mortality.

The clinical efficacy of ischemic stroke is severely limited by the difficulty in targeted delivery of neuroprotective agents across the blood-brain barrier to the ischemic region. Liposomes, with their unique bilayer structure, can carry both hydrophilic and hydrophobic drugs and have excellent biocompatibility, modifiability, and high efficiency in crossing the blood-brain barrier, which have become a key strategy to break through the bottleneck of drug delivery in ischemic stroke treatment. This paper systematically reviews the structural properties of liposomes, their targeted delivery mechanisms, and their cutting-edge applications in ischemic stroke therapy in the past decade, focusing on the precise accumulation of neuroprotective agents in the ischemic region by surface-modified liposomes through the synergistic strategy of active/passive targeting, especially in piggybacking on the active ingredients of TCM. The paper analyzes in depth the latest advances of modified liposomes in inhibiting neuroinflammation, attenuating ischemia/reperfusion injury, combining with tissue plasminogen activator and biomimetic modification of delivery systems. It aims to provide a new theoretical framework for the precise and individualized treatment of ischemic stroke and to provide a reference for the development of neuroprotective agent delivery systems based on liposome technology.

This umbrella review was conducted to assess the certainty and validity of all available meta-analyses for intervention trials regarding the impact of synbiotic and probiotic interventions in hospital and Intensive Care Unit (ICU) stay durations, as well as postoperative mortality risk among patients undergoing surgery.

A comprehensive systematic search was performed by applying Web of Science, Scopus, PubMed, Embase and Cochrane Library until July 20, 2025. Meta-analyses were used to evaluate the effect of synbiotic and probiotic interventions among hospital and ICU stay durations, as well as the postoperative mortality risk in patients undergoing surgery. Effect sizes of synbiotic and probiotic interventions were recalculated by using a random effects model, and the GRADE tool was used to determine evidence certainty.

Forty-eight clinical trials involving 6,378 participants (intervention = 3151; placebo = 3227) across thirty meta-analyses were included in this study. The findings indicated that probiotic supplementation (vs. placebo) significantly reduced the duration of hospital stay [Weighted Mean Difference (WMD): -1.00 days; 95% CI: -1.37 to -0.64; I² = 63.1%; moderate certainty of evidence; P < 0.001; n = 22] among patients undergoing surgery. Synbiotic supplementation showed even greater efficacy, reducing the length of hospital stay by a larger margin (WMD: -2.57 days; 95% CI: -4.51 to -0.64; I² = 83.2%; moderate certainty of evidence; P = 0.009; n = 19). Moreover, the results suggested that synbiotic supplementation did not affect the length of ICU stay. The results indicated that the risk of postoperative mortality did not significantly change after probiotic or synbiotic supplementation (vs. placebo) among patients undergoing surgery.

The current review supports the efficacy of synbiotic and probiotic supplementation on decreasing the length of hospital stay in patients undergoing surgery. However, it is important to note that 42.3% of included systematic reviews and meta-analyses (SRMAs) were rated as 'critically low' quality using the AMSTAR2 tool, which necessitates cautious interpretation of findings.

Metabolic syndrome (METS) is a multifactorial cardiometabolic disorder characterized by abdominal obesity, insulin resistance, hypertension, dyslipidemia, and hyperglycemia, substantially increasing the risk of type 2 diabetes and cardiovascular diseases. The variable effectiveness of lifestyle and pharmacological interventions has heightened interest in complementary approaches. Hirudotherapy, containing a wide range of bioactive compounds, may offer therapeutic benefits. This study aimed to evaluate the effects of hirudotherapy on metabolic parameters in a rat model of METS.

Twenty-four male Wistar rats were divided into four groups: Control (n = 6), METS (n = 6), METS + 4-week hirudotherapy (n = 6), and METS + 8-week hirudotherapy (n = 6). METS was induced through a modified high-fat and fructose-enriched diet. The effects of hirudotherapy on liver enzymes (AST, ALT), lipid profile (TG, LDL cholesterol, HDL cholesterol), hemodynamic parameters (systolic/diastolic blood pressure, mean arterial pressure, heart rate), glucose metabolism (OGTT, AUC), and liver histopathology were assessed. Pellet and water intake were monitored to evaluate possible influences on appetite regulation.

Hirudotherapy demonstrated hepatoprotective activity, yielding significant reductions in AST and ALT levels (p < 0.05). TG levels increased in METS, while LDL cholesterol showed partial improvement and HDL cholesterol remained unchanged. Systolic blood pressure significantly decreased in the hirudotherapy-treated groups, with no significant differences in diastolic pressure or heart rate. OGTT and AUC analyses revealed improved glucose tolerance and reduced hyperglycemia following hirudotherapy (p < 0.05). Histopathology showed marked improvements in steatosis, sinusoidal dilatation, and hydropic degeneration, although minor hemorrhagic foci persisted. Differences in pellet consumption suggested a potential regulatory effect on appetite and metabolic balance.

Hirudotherapy may exert beneficial effects in METS by improving liver function, modulating lipid metabolism, enhancing insulin sensitivity, and reducing inflammation. Its influence on food intake may further support metabolic homeostasis. These findings support hirudotherapy as a potential biotherapeutic approach and warrant further mechanistic and clinical investigations.

Atherosclerosis(AS) is a major cause of cardiovascular and cerebrovascular diseases, with plaque formation and rupture commonly resulting in severe acute cardiovascular events. This study elucidated the spatiotemporal correlations between modern pathological mechanisms of AS and the evolution of traditional Chinese medicine(TCM) pathogenesis from the perspective of the &quot;deficiency, stasis, and toxicity&quot; theory. The temporal progression revealed that AS developed in three dynamic stages, including &quot;deficiency damage&quot; &quot;stasis damage&quot; and &quot;toxicity damage&quot;. In the early stage, lipid metabolism disorders related to vascular endothelial aging served as the initial trigger. The mid-stage was characterized by an inflammatory cascade mediated by macrophages, which drove plaque progression. In the terminal stage, the disease manifested as a systemic inflammatory response and multi-organ dysfunction. The spatial aspect of the disease progression showed that the pathological damage of AS extended from &quot;local lesions&quot; to &quot;regional enlargement&quot; and finally to &quot;systemic involvement&quot;. The pathological process of AS began with the local &quot;deficiency damage&quot; stage of endothelial dysfunction, followed by foam cell aggregation and macrophage infiltration to form the &quot;stasis and toxicity interlock&quot; lesion, leading to pathological damage that spread from local blood vessels to multiple organs. Based on the spatiotemporal evolution mechanism of &quot;deficiency, stasis, and toxicity&quot;, a staged TCM treatment approach was proposed: tonifying deficiency and consolidating body resistance in the early stage, activating blood and resolving stasis in the mid-stage, and detoxifying and unblocking collaterals in the terminal stage. This study integrates modern pathological mechanisms with TCM theory, offering spatiotemporally precise TCM treatment modalities for the treatment of AS.

This study aimed to investigate the therapeutic effect and underlying mechanism of Guizhi Tongluo Tablets in myocardial ischemia-reperfusion injury(MIRI) by regulating the phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt) signaling pathway and inhibiting inflammatory response. Sixty healthy SPF-grade male C57BL/6J mice were randomly divided into sham group, model group, low-dose Guizhi Tongluo Tablets group, medium-dose Guizhi Tongluo Tablets group, high-dose Guizhi Tongluo Tablets group, and nicorandil group. The MIRI model was established by ligating the left anterior descending coronary artery for 30 min followed by reperfusion. Beginning on day 1 after the operation, the mice in the low-, medium-, and high-dose Guizhi Tongluo Tablets groups received 0.51, 1.03, and 2.06 g·kg~(-1)·d~(-1) by gavage, respectively. Mice in the nicorandil group were administered 2.28 mg·kg~(-1)·d~(-1) by gavage. Mice in the sham group and the model group received an equal volume of normal saline once daily by gavage for four consecutive weeks. Cardiac function was assessed via echocardiography. Laser speckle contrast analysis(LASCA) was used to evaluate the microvascular reperfusion in each group. Hematoxylin-eosin(HE) staining was used to observe pathological changes in cardiac tissue, while TUNEL staining was used to detect the apoptosis of cardiomyocytes. The expression levels of inflammatory cytokines interleukin-1β(IL-1β), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α) in the myocardium were measured by qPCR and enzyme-linked immunosorbent assay(ELISA). Transcriptomic sequencing was conducted to identify differentially expressed genes, and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis was used to determine the related pathways. The protein expression levels of PI3K, phosphorylated PI3K(p-PI3K), Akt, and phosphorylated Akt(p-Akt) were analyzed using the Jess automated protein analysis system. The results showed that compared with the sham group, the model group exhibited significantly reduced left ventricular ejection fraction(LVEF) and left ventricular fractional shortening(LVFS), increased infiltration of inflammatory cells in the heart tissue, disorganized cardiomyocyte arrangement, and significantly increased cardiomyocyte apoptosis. Expression levels of IL-1β, IL-6, and TNF-α were markedly upregulated, while the ratios of p-PI3K/PI3K and p-Akt/Akt were significantly decreased. Compared with the model group, mice in the Guizhi Tongluo Tablets groups showed significantly improved cardiac function, reduced inflammatory cell infiltration, partially restored cardiac structure, significantly decreased cardiomyocyte apoptosis and levels of IL-1β, IL-6, and TNF-α, along with significantly increased p-PI3K/PI3K and p-Akt/Akt levels. These findings suggest that Guizhi Tongluo Tablets can effectively prevent and treat MIRI, possibly by activating the PI3K/Akt signaling pathway and alleviating cardiac inflammation.

Ischemic stroke is one of the most severe vascular diseases in the central nervous system, with its pathogenesis involving acute cerebrovascular occlusion leading to local cerebral ischemia and hypoxia, triggering complex pathophysiological cascading reactions. Mitochondrial dysfunction serves as the critical pathological foundation of disease progression, primarily manifesting as significantly enhanced oxidative stress, cellular metabolic disorders, abnormal apoptotic signal activation, amplified inflammatory cascades, and mitochondrial dynamic imbalance. The molecular mechanisms of mitochondrial injury involve multiple key signaling pathways: mitochondrial electron transport chain dysfunction generating substantial reactive oxygen species, calcium overload disrupting mitochondrial membrane potential, and mitochondrial dynamic imbalance leading to fragmentation-fusion disequilibrium. Studies have confirmed that from single herbal active ingredients to compound preparations and even acupuncture and moxibustion, traditional Chinese medicine(TCM) demonstrates multidimensional and multilevel synergistic neuroprotective effects. Focusing on the epidemiological trend of ischemic stroke with a rising incidence, this study delves into mitochondrial dysfunction, the core molecular pathological mechanism of disease occurrence and progression. By systematically elaborating on the multi-target and multi-mechanism intervention strategies of TCM in the neurological protection domain, this study reveals the complex molecular network of mitochondrial damage and highlights the unique therapeutic advantages of TCM in regulating mitochondrial membrane potential, inhibiting oxidative stress, optimizing energy metabolism, and reducing cellular apoptosis. It explores a novel molecular target system for treating ischemic stroke, offering a new theoretical foundation for integrative medicine research.

Chronic heart failure(CHF) represents the terminal phase of severe cardiovascular diseases, with concomitant skeletal muscle atrophy significantly compromising patients' motor function and quality of life, as well as increasing risks of adverse clinical outcomes. Current therapeutic agents and interventions targeting CHF-associated muscle atrophy remain limited. Grounded in a holistic approach and syndrome differentiation, traditional Chinese medicine(TCM) offers unique advantages in managing CHF comorbidities. This review explored the pathological mechanisms underlying skeletal muscle atrophy in CHF through the lens of the &quot;heart Yin deficiency&quot; theory in TCM. A pathogenic triad was proposed, encompassing collateral malnutrition due to Yin deficiency, toxin-stasis interaction, and physical-mental exhaustion. The triad was examined in relation to modern biomedical mechanisms including neuroendocrine dysregulation, oxidative stress-inflammation, microcirculatory dysfunction, and protein metabolic imbalance, highlighting the central role of heart Yin deficiency in disease progression. From the therapeutic perspective of nourishing heart Yin, the multi-target effects of herbal compound formulae and acupuncture therapy in improving cardiac function and alleviating muscle atrophy were analyzed. This analysis aims to provide both theoretical foundations and practical guidance for the clinical management of CHF with skeletal muscle atrophy.

Astaxanthin, a xanthophyll carotenoid derived primarily from Hematococcus lacustris, has been proposed as a potent bioactive compound demonstrating wide therapeutic applicability. In addition to its distinct molecular structure, astaxanthin has exceptional antioxidant property, surpassing that of other carotenoids and conventional antioxidants, while also exerting robust anti-inflammatory effects. The present review focuses on the current evidence of the complex multifaceted therapeutic actions of astaxanthin, including cardiovascular protection, neuroprotection, hepatoprotection, renal support, dermatological health, immune modulation, and emerging roles in metabolic disorders, reproductive health, and cancer prevention. Mechanistic insights highlight its potential to control key molecular mechanisms, including the NF-κB, Nrf2, MAPK, and TGF-β/Smad pathways, alongside the enhancement of endogenous antioxidant defenses. Preclinical and clinical findings have demonstrated benefits in conditions such as atherosclerosis, myocardial ischemia, nonalcoholic fatty liver disease, hypertension, Alzheimer's disease, Parkinson's disease, and inflammatory skin diseases. By integrating evidence drawn from molecular, experimental, and clinical studies, this review underscores astaxanthin's potential as a complementary therapeutic agent and functional nutraceutical. The breadth of its bioactivity positions astaxanthin as a promising natural compound for targeted disease prevention and health promotion.

Pathogenic variants in RAF1 are a common cause of Noonan syndrome (NS), accounting for approximately 5% of cases. Nonetheless, RAF1-related NS is often associated with severe clinical features, particularly hypertrophic cardiomyopathy (HCM). Although initial studies highlighted the occurrence of genotype-phenotype correlations, a comprehensive analysis specifically focused on RAF1 variants is still lacking. We conducted a retrospective observational study combining newly collected cases of RAF1-related NS from a national multicenter retrospective cohort with systematically reviewed cases from a literature search. Variants were classified by protein domain, while the most recurrent variant, p.Ser257Leu, was analyzed separately to assess variant- and domain-specific phenotype correlations. A total of 203 cases were included. Variants in the CR2 domain accounted for 83% of cases, with p.Ser257Leu alone representing 53%. HCM was observed in 80.1% of affected individuals, confirming its role as the predominant cardiac manifestation in RAF1-related NS; neurodevelopmental features were reported in 44.5% of patients. The prevalence of clinical features varied significantly according to variant location. HCM was markedly more frequently associated with CR2 variants (89.4%) and in subjects heterozygous for the p.Ser257Leu change (94.2%) compared with non-CR2 variants (37.1%). Conversely, neurodevelopmental features were more common in patients with non-CR2 variants (69.2%) than in those with CR2 variants (38.2%) or p.Ser257Leu (29.4%). CR2 and p.Ser257Leu variants were associated with earlier age at diagnosis and increased mortality. Our findings confirm and document more comprehensively domain- and variant-specific phenotypes in RAF1-related NS, emphasizing the importance of variant-level interpretation in clinical management and genetic counseling.