搜索结果：Pharmacology

Dendrobium officinale Kimura et Migo (Tiepi Shihu), a yin-nourishing tonic in traditional Chinese medicine, has been historically used for health maintenance and longevity promotion. We evaluated the anti-aging effects of D. officinale whole powder (DOP) and a non-polysaccharide fraction (DOE) and explored underlying mechanisms focusing on conserved PI3K-AKT signaling. Network pharmacology was applied to predict aging-related targets and enriched pathways. Anti-aging activity was assessed in yeast (Saccharomyces cerevisiae) and female flies (Drosophila melanogaster) using lifespan and healthspan assays, a high-sugar diet challenge, and pathway readouts via qRT-PCR and Western blotting. In RAW264.7 macrophages, the PI3K inhibitor LY294002 and the AKT inhibitor MK-2206 were used to evaluate pathway dependence. Network pharmacology identified 355 overlapping targets, enriched in PI3K-AKT, MAPK, Ras, and HIF-1 pathways. We found that dihydroconiferyl alcohol, homovanillyl alcohol, and taxifolin extended yeast lifespan, and these effects were abolished in yeast mutants defective in key aging-related genes. In flies, DOP extended female lifespan, improved climbing performance, and mitigated high-sugar diet-induced lifespan loss and hyperglycemia, accompanied by reduced AKT phosphorylation under dietary stress and enhanced FOXO-associated responses. DOE also extended lifespan, increased AKT/S6K phosphorylation and reduced FOXO in flies. D. officinale was associated with context-dependent modulation of innate immune-related gene expression. However, DOE suppressed AKT activity and increased FOXO in RAW264.7 cells; co-treatment with MK-2206 abolished DOE-induced changes. D. officinale exerts anti-aging effects in yeast and Drosophila models, while mammalian macrophages support a mechanistic role for context-dependent PI3K-AKT signaling regulation. Its distinct fractions act in a context-dependent manner, with AKT serving as a central regulatory node and FOXO-associated responses, supporting its ethnopharmacological use as a longevity-promoting herb.

Allogeneic hematopoietic stem cell transplantation is an established curative therapy for many hematological diseases, but graft-versus-host disease remains a major cause of morbidity and mortality. Tacrolimus, a calcineurin inhibitor, is widely used for prophylaxis because it suppresses T-cell activation. However, its clinical use is complicated by a narrow therapeutic window and marked pharmacokinetic variability. Therapeutic drug monitoring based on trough whole-blood concentrations is routinely used to guide dosing, but this approach has limitations, particularly in transplantation recipients who experience rapid physiological and hematological changes. This review summarizes recent insights into determinants of tacrolimus pharmacology in hematopoietic stem cell transplantation and discusses emerging perspectives for individualized dosing. Tacrolimus exerts its immunosuppressive effects by forming a complex with FK506-binding proteins that inhibits calcineurin and suppresses activation of nuclear factor of activated T cells. Beyond this canonical mechanism, interactions with FK506-binding proteins influence the distribution of tacrolimus within blood cells. Because tacrolimus strongly divides into erythrocytes and leukocytes, whole-blood concentrations reflect systemic exposure and drug binding within circulating blood components. In recipients of hematopoietic stem cell transplantation, marked fluctuations in blood cell counts during conditioning therapy and hematopoietic recovery can alter this distribution, potentially causing changes in concentrations without corresponding changes in pharmacologically active exposure. Genetic variation in drug-metabolizing enzymes further contributes to variability in tacrolimus pharmacokinetics. In particular, polymorphisms in the gene encoding cytochrome P450 3A5 influence tacrolimus metabolism and may affect early dose requirements during the post-transplant period. Additionally, temporal fluctuations in tacrolimus exposure within individual patients are increasingly recognized as clinically relevant. Measures that capture the proportion of time during which concentrations remain within the therapeutic range provide a useful indicator of exposure stability. Tacrolimus therapy after hematopoietic stem cell transplantation is influenced by molecular pharmacology, blood cell-dependent distribution, genetic determinants of metabolism, and temporal variability in drug exposure. Integrating these factors may improve understanding of therapeutic drug monitoring and promote more individualized strategies to maintain stable immunosuppression and improve transplant outcomes.

Multidrug-resistant Stenotrophomonas maltophilia pneumonia lacks effective therapies. Quercetin, a natural flavonoid with anti-inflammatory properties, may offer benefit, but its mechanism remains unclear. We characterized a clinical S. maltophilia isolate, predicted quercetin targets via network pharmacology, validated interactions through molecular docking and 100 ns dynamics simulations, and evaluated efficacy in a murine pneumonia model using histopathology, western blotting, qPCR, and immunohistochemistry. The isolated H-SMA strain exhibited multidrug resistance (resistant to β-lactams, macrolides, aminoglycosides) but remained susceptible to enrofloxacin. Network pharmacology identified eight core inflammatory/apoptotic targets (TNF, IL6, IL1B, IL10, IFNG, CASP3, BCL2, AKT1). Molecular docking and 100 ns dynamics simulations confirmed stable quercetin binding to all targets, with strongest interactions with AKT1 (-8.4 kcal/mol) and CASP3 (3-5 stable hydrogen bonds). In vivo, quercetin (100 mg/kg/d) significantly ameliorated clinical symptoms, reversed body weight loss, attenuated pulmonary histopathological damage, and restored splenic architecture, achieving efficacy comparable to enrofloxacin. Mechanistically, quercetin inhibited phosphorylation of AKT, IκBα, and NF-κB p65, restored Bcl-2/Bax balance, and reduced cleaved Caspase-3 expression. At the transcriptional level, quercetin downregulated pro-inflammatory (TNF, IL1B, IL6, IFNG) and pro-apoptotic (CASP3) genes while upregulating anti-inflammatory (IL10) and anti-apoptotic (BCL2) genes. Immunohistochemistry confirmed reduced pulmonary NF-κB p65 nuclear translocation and cleaved Caspase-3 positivity. Quercetin alleviates S. maltophilia pneumonia through multi-target modulation of AKT/NF-κB signaling and apoptosis pathways, supporting its potential as host-directed therapy for drug-resistant bacterial infections.

Renal lipid metabolic dysregulation drives tubular injury and fibrosis in chronic kidney disease (CKD), yet endogenous targets governing tubular lipid homeostasis remain incompletely understood. This study aimed to elucidate how calycosin (CAL), an O-methylated isoflavone from Astragali Radix, corrects renal lipid metabolic dysregulation and attenuates fibrosis in CKD. An adenine-induced CKD mouse model and TGF-β1-stimulated HK-2 cells were treated with CAL. Lipidomics and network pharmacology screened candidate targets. Surface plasmon resonance (SPR) and molecular dynamics simulation validated target binding. Adeno-associated virus (AAV)-mediated renal phosphoenolpyruvate carboxykinase 1 (PCK1) overexpression in vivo and lentiviral overexpression in vitro established the regulatory relationship. The PCK1 inhibitor 3-mercaptopicolinic acid served as reverse validation. CAL improved renal function, alleviated fibrosis, and reduced lipid deposition both in vivo and in vitro. Lipidomics revealed that CAL bidirectionally modulated renal lipid metabolism by suppressing glycerophospholipid, sphingolipid, and glycerolipid accumulation while restoring omega-3 PUFA-enriched lipids and decreasing lipid saturation. SPR confirmed direct binding of CAL to PCK1. Gain-of-function experiments demonstrated that PCK1 negatively regulates Twist family BHLH transcription factor 1 (TWIST1) in the kidney. Accordingly, CAL activated the PCK1/TWIST1/carnitine palmitoyltransferase 1 A (CPT1α) axis, restoring fatty acid oxidation and suppressing lipid uptake, thereby attenuating lipotoxicity-driven oxidative stress and tubular apoptosis. This study identifies PCK1 as an endogenous binding target of CAL in the kidney and delineates the PCK1/TWIST1/CPT1α axis as the downstream signaling circuitry through which CAL corrects tubular lipid metabolic disorders and attenuates renal fibrosis, providing mechanistic rationale for targeted CKD therapy.

UVB-induced lens epithelial cell (LEC) senescence is among the important factors involved in the pathogenesis of age-related cataract (ARC). This study aimed to investigate the anti-aging effect of metformin (Met) and to elucidate the molecular mechanisms underlying this effect. RNA sequencing, nontargeted metabolomics analysis and network pharmacology were conducted. The expression of senescence indicators (P53 and P21Cip1) and senescence-associated β-galactosidase (SA-β-gal) activity were assessed. Mitochondrial function and dynamics were evaluated by measuring the mitochondrial membrane potential (MMP), transmission electron microscope (TEM), and Western blotting. Cytosolic mtDNA was visualized by fluorescence staining, and the activation of the SIRT1-PGC-1α pathway and the cGAS-STING pathway were analysed by Western blotting. Our findings indicated that cellular senescence was predominantly responsible for UVB-induced cataract. Met attenuated UVB-induced cataract by inhibiting the senescence phenotype. Mechanistically, Met activated the SIRT1-PGC-1α pathway to inhibit mitochondrial fragmentation. This attenuation of mitochondrial fragmentation reduced mtDNA release into the cytosol, thereby inhibiting the activation of the cGAS-STING-mediated LEC senescence. Our findings on the efficacy of Met pave the way for the development of new pharmacological strategies to prevent cataract development.

Euphorbia milii Des Moul is a plant with a long history of use in traditional medicinal and is widely distributed across tropical and subtropical regions. Traditionally, its sap has been used in folk medicine to treat various conditions such as skin inflammations, pain, and boils. To date, it remains a commonly used herbal medicine in clinical practice. This paper systematically reviews the phytochemistry, pharmacology and toxicology of E. milii to assess its therapeutic potential and guide future studies. A comprehensive literature search was performed based on multiple s databases, including Web of Science, ScienceDirect, PubMed, Elsevier, CNKI, VIP, and Wanfang. Additionally, taxonomic databases such as Flora of China and Plants of the World Online (POWO) were consulted to verify the plant's nomenclature and distribution. To date, 85 compounds have been identified from E. milii, comprising 74 diterpenoids, 6 triterpenoids, 2 steroids, 2 flavonoids, and 1 macrocyclic lactone. These phytochemicals exhibit a broad spectrum of pharmacological activities, including analgesic, anti-inflammatory, antioxidant, antimicrobial, anticancer, anti-gout, molluscicide, and anti-parasitic effects. Given its long history of traditional use, rich phytochemical composition, and diverse pharmacological activities, E. milii can be considered an important botanical resource for applications not only in traditional medicine but also in modern ecological and potential pharmacological contexts. However, in vivo and clinical studies remain limited. Future research should emphasize pharmacokinetic profiling to strengthen the basis for clinical applications and new drug development.

Macrophages are central regulators of skeletal muscle regeneration, dynamically transitioning from pro-inflammatory (M1-like) to reparative (M2-like) phenotypes to coordinate debris clearance, inflammation modulation, satellite cell activation, and tissue remodeling. This review details the underlying molecular mechanisms, focusing on metabolic reprogramming, such as the shift to oxidative phosphorylation and key roles of AMPK, lactate, and glutamine metabolism. It further examines the transcriptional networks (e.g., PPARγ, Nfix) and multicellular crosstalk that shape the regenerative niche. We analyze macrophage dysfunction in pathological contexts: aging-related impairments in dynamics and metabolism that hinder repair, and in Duchenne Muscular Dystrophy (DMD), where sustained inflammation and trained immunity drive fibrosis. Current challenges include deciphering macrophage heterogeneity beyond the M1-like/M2-like paradigm and bridging translational gaps between models and human disease. The review outlines therapeutic strategies to reprogram macrophage function, spanning pharmacological agents (AMPK/PPARγ agonists, cytokine/chemokine modulation), nanotechnology, cell therapies (e.g., exosomes), and physical interventions. A key feature is the integration of molecular docking analyses, revealing structural interactions between compounds (e.g., AICAR, Cenicriviroc) and targets like AMPK, PPARγ, CCR2, and CCR5. This provides a structural pharmacology foundation for developing targeted immunometabolic therapies to restore muscle regeneration in injury and degenerative diseases.

Central nervous system (CNS) metastases from Wilms tumor (WT) are exceedingly rare. Intracerebral hemorrhage secondary to metastatic WT is even less common, and the management of such cases is further complicated when patients are receiving a direct oral anticoagulant (DOAC) like Rivaroxaban, for which pediatric reversal guidelines are lacking. We report on the case of a 5-year-old boy with relapsed stage IV Wilms tumor who presented with rapidly progressive neurological deterioration caused by brain metastases with extensive intraparenchymal and intraventricular hemorrhage while receiving Rivaroxaban due to prior thrombosis. An emergent craniotomy and tumor resection was safely performed after emergent reversal of anticoagulation with Rivaroxaban using Andexanet alfa, administered in this pediatric patient with off-label consent in the setting of a life-threatening intracranial hemorrhage requiring emergent neurosurgical intervention. No excessive intraoperative bleeding was noted. Treatment for relapsed WT according to the SIOP-UMBRELLA-Protocol was initiated. Three weeks after Andexanet alfa treatment, a thrombotic event in the left iliac veins occurred, requiring anticoagulation with unfractionated heparin. This case highlights the therapeutic challenges of managing intracranial hemorrhage in a pediatric patient requiring emergent neurosurgical debulking in the setting of Rivaroxaban anticoagulation. To our knowledge, this is the second case reporting on Rivaroxaban reversal through Andexanet alfa in children. Early multidisciplinary intervention, meticulous neurosurgical management and continuation of oncologic therapy can lead to favorable outcomes even in such complex presentations.

Demyelination and impaired remyelination are hallmark features of many neurodegenerative and psychiatric disorders. Although central mechanisms have been widely investigated, the contribution of peripheral immune organs such as the spleen remains poorly understood. In this study, we examined the role of the spleen and transforming growth factor-β1 (TGF-β1) in cuprizone (CPZ)-induced demyelination and remyelination in mice. Splenectomy performed before CPZ exposure significantly worsened demyelination in the corpus callosum, as indicated by reduced myelinated area and myelin basic protein (MBP) intensity. Likewise, splenectomy immediately after CPZ withdrawal markedly impaired remyelination during the recovery phase. Immunohistochemical analysis showed that splenectomy reduced TGF-β1 expression in the corpus callosum at both 2 and 7 weeks after surgery. Moreover, systemic administration of a neutralizing anti-TGF-β1 antibody during either the demyelination or remyelination phase reproduced the effects of splenectomy, resulting in greater myelin loss or reduced myelin repair, respectively. Antibody treatment significantly decreased TGF-β1 levels in both brain and plasma, which were positively correlated with the degree of myelination. Together, these findings reveal a previously unrecognized role of the spleen in preserving myelin integrity and facilitating repair through TGF-β1 signaling. They further suggest that the spleen-brain axis contributes to myelin homeostasis and that peripheral TGF-β1 may represent a potential biomarker and therapeutic target for demyelinating disorders.

Patients with Down Syndrome (DS) are characterized by dysfunction of several organs, including the liver, brain, heart defects, gastrointestinal anomalies, and lethal immune hypersensitivity. A person with DS is also susceptible to various inflammatory diseases, including hepatic autoimmune diseases. The Cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) is known to trigger the stimulator of interferon genes (STING) and downstream proinflammatory factors. In this work, we hypothesized that oxidative stress-associated DNA damage triggers activation of the cGAS-STING signaling pathway and promotes liver inflammation in DS. Here, we investigated the role of reactive oxygen species (ROS) associated DNA damage and the cGAS-STING signaling pathway in the pathogenesis of hepatic inflammation in the DS model. Our results showed that DS cells harbor excessive ROS and DNA damage in DS fibroblasts and DS mouse liver. Further, DS cells accumulate micronuclei that likely serve as a source of cytoplasmic DNA to stimulate cGAS-STING activation. In addition, RNA-seq analysis results showed enhanced expression of key type I interferon factors in cGAS-STING pathways in DS liver and inflammatory responses and elevated liver enzymes such as alanine transaminase (ALT) that indicate a hepatocellular liver injury in DS. The results of this study opened the opportunity to connect endogenous DNA damage triggers innate immune response, which may contribute to the upregulation of the cGAS-STING signaling to exacerbate hepatic inflammation in DS.

TkMYC2 mediates jasmonate-induced drought resistance and rubber biosynthesis simultaneously in Taraxacum kok-saghyz. Taraxacum kok-saghyz (T. kok-saghyz) is an important natural rubber-producing plant, yet its cultivation is often limited by drought stress, and the regulatory mechanisms underlying rubber biosynthesis and laticifer development remain incompletely understood. This study focused on TkMYC2, a core transcription factor in the jasmonate (JA) signaling pathway. Through homologous and heterologous genetic transformation, we systematically elucidated its dual functions in conferring drought tolerance and driving rubber biosynthesis. TkMYC2 expression was induced by both drought and methyl jasmonate (MeJA). Overexpression of TkMYC2 significantly enhanced the tolerance of transgenic plants to osmotic and drought stress by activating the antioxidant system (SOD, POD, CAT), maintaining ROS homeostasis, and reducing membrane lipid peroxidation. Using yeast two-hybrid and bimolecular fluorescence complementation assays, we demonstrated a direct physical interaction between TkMYC2 and TkJAZ11, a key repressor in the JA pathway. Phenotypic analyses showed that TkMYC2 overexpression promoted root thickening, laticifer development, and natural rubber accumulation, functionally supporting the hypothesis that rubber biosynthesis drives laticifer development. In summary, TkMYC2 acts as a critical molecular hub concurrently regulating drought stress response and rubber biosynthesis, providing new insights into jasmonate-mediated coordination of stress resilience and secondary metabolism, and offering a genetic resource for molecular breeding of T. kok-saghyz with enhanced yield and stress tolerance.

Social defeat stress (SDS) is a rodent model used to assess the effect of chronic stress on depressive-like behavior and alcohol consumption. Our previous studies have indicated that the neurokinin-1 receptor (NK1R) mediates the behavioral responses to this stressor, especially through its actions in the nucleus accumbens (NAc). The NK1R is the high affinity, endogenous target of the neuropeptide substance P (SP). In the experiments presented here, we first infused a cre-dependent, retrogradely transported virus into the NAc of Tac1-cre mice (Tac1 is the gene for SP) to identify brain regions that send SP-expressing inputs to the NAc. We found that significant SP projections originated in the paraventricular nucleus of the thalamus (PVT). Next, we used this same tracing strategy, exposed mice to SDS or control conditions, and assessed Fos expression in the PVT. This experiment confirmed that SP projections from the PVT to the NAc are activated by SDS. To chemogenetically manipulate SP innervation of the NAc, we bilaterally infused a cre-dependent, retrogradely transported virus that expresses an inhibitory DREADD receptor into the NAc of Tac1-cre mice and delivered the DREADD actuator clozapine-n-oxide (CNO) prior to each defeat exposure. We found that this treatment had no effect on SDS-induced social avoidance, but did reduce alcohol consumption after stress. In a following experiment, CNO was administered just prior to behavioral testing, as opposed to during stress. In line with the previous experiment, chemogenetic inhibition affected post-stress drinking, but not social interaction. Conversely, chemogenetic activation of these inputs acutely increased alcohol consumption without affecting social behavior. Together, these results show that SP projections from the PVT to the NAc are activated by SDS exposure, and suggest that SP innervation of the NAc, possibly from the PVT, mediates post-stress alcohol consumption.

The prehospital management of moderate/severe traumatic brain injury (TBI) centers on preventing secondary brain injury. Prehospital emergency anesthesia (PHEA) may be required for optimal neuroprotective care. Continuous invasive arterial blood pressure (IBP) monitoring is increasingly used in this cohort. PHEA can result in significant blood pressure (BP) changes, particularly around induction. IBP allows targeted BP management. This study analyzed hypotension frequency, depth, and duration in patients with suspected TBI monitored with IBP before PHEA. This was a retrospective analysis of patients with suspected TBI attended by Air Ambulance Charity Kent Surrey Sussex (KSS) who received IBP before PHEA between January 6, 2022, and July 6, 2024. The magnitude and duration of "absolute hypotension" (systolic BP [SBP], < 90 mm Hg) were combined to establish a dose of absolute hypotension (mm Hg &#xd7; minutes). The primary endpoints were incidence and dose of absolute hypotension. A total of 305 patients were identified; 140 (45.9%) were included. The median age was 58 years (interquartile range [IQR], 42-73), the predominant sex was male (n = 108; 77%), and the median Glasgow coma scale score was 6/15 (IQR, 4.0-7.5). Thirteen patients (9.3%) had absolute hypotension before PHEA, increasing to 53 (37.9%) after PHEA. Twenty-five patients (47.2%) had initial absolute hypotensive episodes that occurred 5 minutes after PHEA, with a median duration of 3 minutes (IQR, 1.0-4.5). The median dose of absolute hypotension was 144 mm Hg &#xd7; minutes (IQR, 3.75-1,675.5). Twenty-five patients (17.9%) had "clinically important hypotension" (SBP, < 110 mm Hg) before PHEA, increasing to 80 after PHEA (57.1%). Pre-PHEA absolute and clinically important hypotension were associated with both incidence and dose of post-PHEA absolute hypotension. This study highlights a higher incidence of absolute hypotension using IBP than previous studies using intermittent noninvasive monitoring. Although post-PHEA absolute hypotension was common, more than half of these events were brief (< 5 minutes). These findings highlight the importance of analyzing hypotension depth and duration and suggest the need for prehospital outcome-based studies using continuous IBP.

The gut microbiome supports digestion, immunity, and metabolism; its imbalance (dysbiosis) drives inflammation and metabolic dysfunction, contributing to chronic diseases such as diabetes, cardiovascular disease, inflammatory bowel disease, and autoimmune disorders. Medicinal plants provide a wide range of phytochemicals (such as polyphenols, flavonoids, alkaloids, saponins), which reach the colon and undergo two-sided interactions with microbes in the gut, acting as potential microbiome modulators and substrates of biotransformation into bioactive metabolites. This structured narrative review synthesises evidence from peer-reviewed studies indexed in PubMed, Scopus, and Web of Science over the last 10 years on the role of medicinal plants in microbiome-mediated chronic disease modulation. This literature is organised into three mechanistic axes: (i) perturbations, defined here as measurable shifts in microbial diversity or taxonomic composition relative to a baseline or healthy reference state, together with beneficial taxa enrichment; (ii) alterations in microbial metabolite output, especially short-chain fatty acids (SCFAs) and other immunometabolic mediators; and (iii) downstream host metabolic and immune signalling. Rather than broad descriptive summaries, the literature is organised using an axis-based mechanistic framework, highlighting key translational constraints such as botanical heterogeneity, dose/formulation variability, and inconsistent microbiome endpoint standardisation, that must be addressed to strengthen human evidence and clinical relevance. Illustrative microbiome-mediated processes involve botanicals such as turmeric (curcumin), ginseng (ginsenosides), and green tea (catechins), though evidence strength varies by study design. Future progress requires standardised phytochemical characterisation, microbiome-stratified trials, and integration of multi-omics with artificial intelligence analytics to enhance mechanistic insight, identify responders, and enable personalised plant-based microbiome therapies.

Anxiety among adolescents has increased globally during the COVID-19 pandemic. Adolescents in juvenile detention centers (JDCs) may be particularly vulnerable due to restricted liberty and social isolation. Movement-based interventions such as Dance/Movement Therapy (DMT) have been studied as approaches to support emotional regulation. This exploratory study investigated the psychophysiological effects of a structured DMT intervention on anxiety reduction among adolescents in JDCs, focusing on anxiety-related changes in dopamine (DA) levels and body temperature. This quasi-experimental study included 55 female adolescents from a single juvenile detention center. Participants were allocated to either a non-DMT control group (n&#x2009;=&#x2009;30, 16.17&#x2009;&#xb1;&#x2009;1.73 years), which maintained their usual institutional routine throughout the 8-week study period, or a DMT group (n&#x2009;=&#x2009;25, 16.23&#x2009;&#xb1;&#x2009;1.68 years) that completed 24 DMT sessions over the same period. Anxiety and physiological measures were assessed before and after the intervention. Anxiety was measured using the Beck Anxiety Inventory (BAI). Physiological measures included mean body temperature (mTb), calculated from tympanic (core) and skin temperature measurements, and plasma DA levels measured using high-performance liquid chromatography (HPLC). Following the intervention, the DMT group showed a significant reduction in BAI scores (-16%, p&#x2009;<&#x2009;0.001), along with significant increases in mTb (0.11&#x2009;&#xb1;&#x2009;0.07&#xa0;&#xb0;C, p&#x2009;<&#x2009;0.001) and DA levels (+&#x2009;30%, p&#x2009;<&#x2009;0.001). BAI scores were negatively correlated with mTb and DA levels, whereas mTb was positively correlated with DA levels. This study provides preliminary evidence that DMT may help alleviate anxiety and support psychophysiological regulation among adolescents in JDCs. However, the exploratory design, single-center setting, and all-female sample may limit generalizability. Future multi-center studies with more diverse samples are needed to confirm these findings and clarify the underlying mechanisms.

Monitoring biochemical parameters is an essential component of pharmacological safety and routine clinical practice. Abnormalities in hepatic and renal function observed during hospitalization may reflect pharmacological exposure, underlying disease processes, or their interaction. However, real-world data describing the frequency and distribution of such laboratory abnormalities in hospital settings remain limited. This study aimed to evaluate the prevalence of biochemical abnormalities of hepatic and renal function among patients receiving pharmacological therapy and to assess the frequency of laboratory alterations associated with commonly prescribed drug groups. A retrospective observational study was conducted using laboratory data from the Department of Clinical Biochemistry. The analysis included 3,500 adult patients who underwent biochemical testing while receiving pharmacological therapy between January 2023 and December 2025. The evaluated parameters included alanine aminotransferase, aspartate aminotransferase, serum creatinine, urea, sodium, and potassium. Patients were categorized according to the main pharmacological therapy received, including antibiotics, non-steroidal anti-inflammatory drugs, and antihypertensive medications. Abnormal values were defined according to institutional laboratory reference ranges. Among the 3,500 patients included in the analysis, 52.3% were male and 47.7% were female, with a mean age of 56.8&#xb1;15.4 years. Antibiotics were prescribed to 41.6% of patients, non-steroidal anti-inflammatory drugs to 33.2%, and antihypertensive medications to 25.2%. Elevated alanine aminotransferase levels were observed in 18.9% of patients, while increased aspartate aminotransferase levels were detected in 15.4%. Hepatic enzyme abnormalities were more frequently observed among patients receiving antibiotics and non-steroidal anti-inflammatory drugs, with statistically significant differences between therapy groups (p<0.05). Renal function abnormalities were identified in 14.7% of patients for creatinine and 12.9% for urea, particularly among patients treated with non-steroidal anti-inflammatory drugs. Electrolyte disturbances were less frequent, with hyponatremia observed in 6.1% and hyperkalemia in 4.3% of cases. Overall, 27.6% of patients exhibited at least one clinically relevant biochemical abnormality during hospitalization while receiving pharmacological therapy. A considerable proportion of hospitalized patients receiving pharmacological therapy present with clinically significant biochemical abnormalities affecting hepatic, renal, or electrolyte parameters. Although causality cannot be established in this retrospective design, these findings underscore the importance of systematic laboratory monitoring as part of hospital-based pharmacovigilance and patient safety strategies.

Danshensu (DSS) is one of the water-soluble components extractable from the traditional Chinese medicine Salvia miltiorrhiza Bge., exhibiting pharmacological effects such as promoting blood circulation, dilating coronary arteries, and improving cerebral blood flow. The Danshensu derivative (OZD-1) obtained through the derivatization of DSS is a potential multi-target drug for the central nervous system, however, its mechanism of action against cerebral ischemia-reperfusion injury (CIRI) remains unclear. Systematically investigating the therapeutic potential and mechanisms of action of Danshensu derivative against cerebral ischemia-reperfusion injury. Rat brain microvascular endothelial cells (RBMVECs) were cultured in vitro to establish an oxygen-glucose deprivation/reoxygenation (OGD/R) injury model. Groups included a control group, an OGD/R model group, and OZD-1 low-dose (12.5 &#x3bc;mol/L), medium-dose (25 &#x3bc;mol/L), and high-dose (50 &#x3bc;mol/L) groups. Cell viability, migration capacity, and vascular lumen formation were assessed using the CCK-8 assay, cell scratch assay, and matrigel matrix gel assay, respectively. In vivo, a transient middle cerebral artery occlusion (tMCAO) model was established in rats. Animals were randomly divided into the sham, model, OZD-1 (35, 70, 140 mg/kg), Edaravone (Eda), and DSS groups. Daily oral administration was performed post-surgery for 14 consecutive days. Tissue pathology staining, behavioral tests, and regional cerebral blood flow imaging assessed brain tissue damage, cognitive function, and ischemic side cerebral blood flow recovery, respectively. Transcriptome sequencing analyzed differential gene expression and pathway enrichment patterns. Western blot detection measured expression levels of proteins related to the PI3K-AKT-CREB signaling pathway, phosphoproteins, downstream apoptosis-related proteins, and CD31, CD34, and VEGFA proteins. In vitro experiments demonstrated that OZD-1 dose-dependently enhanced the viability of RBMVECs following OGD/R injury, significantly improving cell migration and luminal formation capabilities. In vivo studies revealed that compared to the model group, rats in all OZD-1 dosage groups exhibited markedly improved cognitive function, significantly restored cerebral blood flow in the ischemic hemisphere, and substantially reduced pathological brain tissue damage. Transcriptome sequencing results indicated significant enrichment of genes associated with the PI3K-AKT signaling pathway following OZD-1 intervention. Western blot experiments confirmed that OZD-1 significantly upregulates the phosphorylation levels of proteins related to the PI3K-AKT-CREB signaling pathway in OGD/R-injured cells and brain tissue from tMCAO rats, thereby promoting VEGFA-mediated angiogenesis and inhibiting apoptosis. To further verify pathway involvement, in vitro inhibition experiments were performed in RBMVECs using the PI3K inhibitor LY294002 and CREB inhibitor 666-15. These inhibitors abolished the OZD-1-induced upregulation of p-PI3K, p-AKT, and p-CREB, and reversed its protective effects on cell viability, migration, and tube formation. These results confirm that OZD-1 protects vascular endothelial cells directly via activating the PI3K-AKT-CREB pathway. OZD-1 exhibits significant neuroprotective effects against CIRI in rats, improving cognitive function, promoting vascular regeneration in ischemic areas, repairing damaged RBMVECs, and reducing apoptosis. Its mechanism of action is associated with the activation of the PI3K-AKT-CREB-VEGFA signaling pathway.

This review synthesizes best practices for ambulatory pediatric tonsillectomy with or without adenoidectomy in ambulatory surgery centers. It emphasizes rigorous patient selection-particularly for severe obstructive sleep apnea, age, obesity, and complex comorbidities-along with individualized anesthetic plans (induction and airway choice), multimodal opioid-sparing analgesia, and robust post-operative nausea and vomiting prophylaxis. Standardized post-anesthesia care unit monitoring, discharge criteria, caregiver education, and escalation pathways address common complications (airway events, hemorrhage, pain, dehydration). Preparedness-pediatric advanced life support-certified staff, emergency equipment, and transfer agreements-underpins safety. Quality-improvement initiatives and emerging tools offer avenues to further reduce morbidity and unplanned admissions.

The number of patients taking glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose co-transporter 2 (SGLT 2) inhibitors presenting for elective surgery is increasing. Patients taking GLP-1 RAs with the highest risk of aspiration are non-fasters who have recently initiated the drug, have had a recent dose escalation, and/or have active gastrointestinal symptoms. Asymptomatic patients on stable doses of GLP-1 RAs can continue the medication throughout the peri-operative period. SGLT 2 inhibitor use carries a risk of euglycemic diabetic ketoacidosis, particularly in patients on insulin with prolonged fasting and should be held prior to elective procedures.