Baloxavir marboxil (Xofluza™) was initially approved for marketing in Japan and the United States in 2018, which is a first-in-class cap-dependent endonuclease inhibitor of the influenza virus polymerase PA subunit. Despite indicating that Baloxavir marboxil is effective and well-tolerated through a series of clinical trials, studies on its safety in real-world settings are scarce. We conducted a mining analysis of the FDA Adverse Event Reporting System (FAERS) database from Q4 2018 to Q2 2024 to extract adverse events associated with Baloxavir marboxil. Descriptive statistics were first performed to characterize the included reports, covering demographic variables, clinical outcomes, and concomitant medications. We subsequently employed four disproportionality analysis algorithms—ROR, PRR, BCPNN, and MGPS—for signal detection. To verify the robustness of the identified signals, we performed comprehensive subgroup and sensitivity analyses. A total of 1,765 reports comprising 3,624 adverse events with baloxavir marboxil as the primary suspected drug were identified. Most reports originated from the United States (57.98
Infliximab (IFX) is a cornerstone biologic for pediatric inflammatory bowel disease, where therapeutic drug monitoring (TDM) is essential but complicated by inter-platform variability. Systematic comparison of automated immunoassays with reference methods is therefore warranted. This study aimed to validate an in-house chemiluminescence immunoassay (CLIA) for IFX quantification and evaluate its agreement with liquid chromatography-tandem mass spectrometry (LC-MS/MS). A CLIA kit was validated by assessing the limit of blank, specificity, linearity, accuracy, precision, matrix equivalence, and stability. IFX concentrations in 52 pediatric plasma samples were measured by CLIA and a reference LC-MS/MS method. Comparability was evaluated using linear regression, Passing-Bablok regression, and Bland-Altman analysis. CLIA showed excellent performance (lower limit of quantification: 0.640 µg/mL; specificity <10.0% interference; reportable range: 0.640-462 µg/mL). LC-MS/MS yielded higher concentrations than the CLIA (median: 6.25 vs. 2.87 µg/mL). Strong correlation was observed (r = 0.9101) with no significant deviation from linearity (Passing-Bablok, p > 0.05). However, Bland-Altman revealed substantial mean relative bias (67.9%) and poor categorical agreement (52% concordance) within the therapeutic range (3-7 µg/mL), indicating non-interchangeability. We validated a rapid, automated CLIA suitable for high-throughput TDM. Despite strong correlation, significant quantitative differences preclude direct result substitution, underscoring the need for method-specific therapeutic thresholds.
Background:Surgical site infection (SSI) prevention is a critical component of pediatric surgical safety, yet the irrational prolongation of perioperative antimicrobial prophylaxis (PAP) remains a global driver of antimicrobial resistance (AMR). While guidelines explicitly recommend discontinuing prophylaxis within 24 h for clean incisions, compliance varies significantly. This study aimed to evaluate the knowledge, attitudes, and practices (KAP) of pediatric surgeons regarding PAP and to identify the determinants of non-compliant behaviors using a novel clustering approach. Methods:A multicenter, cross-sectional study was conducted from July to August 2025 across Children's hospitals in Jiangsu Province, China. A total of 143 surgeons from different surgical departments (e.g., General Surgery, Orthopedics, Neurosurgery, Cardiothoracic Surgery) were surveyed using a validated questionnaire based on WHO guidelines. Data were analyzed using Spearman's rank correlation to assess knowledge-practice associations and K-Means clustering to identify distinct behavioral patterns among clinical departments. Results:The study achieved a valid response rate of 95.3%. While surgeons demonstrated high cognitive accuracy regarding drug selection (>84.0%) and administration timing (95.1%), only 74.8% acknowledged the standard of discontinuing prophylaxis within 24 h for Class I incisions. A significant positive correlation was found between knowledge and practice scores (r = 0.579, P < 0.001). However, cluster analysis revealed a "Knowledge-Practice Disassociation" pattern in the Oncology, Burns, and SICU departments. Conclusion:A high level of cognitive reserve cannot ensure consistent implementation of standard practices. In high-risk departments, clinicians' focus on SSI rather than AMR may trigger defensive medicine, which is likely to impair guideline adherence. This association requires further verification in targeted investigations.
IntroductionUnderstanding geographic inequalities in psychotropic medication dispensing is important for improving health equity and informing place‐based pharmaceutical management. This study characterized the spatiotemporal distribution of methylphenidate hydrochloride extended‐release tablet dispensing in Jiangsu Province, China, from 2019 to 2023 and examined its socioeconomic and education‐related correlates.MethodsAnnual county‐level dispensed tablet volumes were analyzed using Getis–Ord Gi* hot‐spot analysis, standard deviational ellipses, and weighted‐centroid analysis. Prefecture‐level contextual correlates were examined using annual Lasso models interpreted with SHAP.ResultsThe proportion of county‐level units with zero recorded dispensing decreased from approximately 52%–36%, while the proportion with annual volumes exceeding 20,000 tablets increased from 7% to 20%. Southern Jiangsu consistently exhibited higher dispensing volumes than Northern Jiangsu, with Central Jiangsu generally occupying an intermediate position. Getis–Ord Gi* identified localized high‐value concentrations mainly in Southern and parts of Central Jiangsu. The standard deviational ellipse area increased by 23.1%, while the weighted centroid remained in south‐central Jiangsu. Within the annual Lasso models, predictive importance was allocated mainly to economic‐demographic indicators in 2019–2020 and more strongly to education‐related indicators in 2021–2023.DiscussionThe findings support geographically differentiated monitoring of medication access, dispensing patterns, and prescribing quality.
Perampanel (PER), the first high-selectivity, non-competitive AMPA-type glutamate receptor antagonist approved for clinical use, plays a pivotal role in the management of drug-resistant epilepsy. However, its clinical application faces significant challenges: pronounced interindividual variability in pharmacokinetics and pharmacodynamics results in both antiseizure efficacy and adverse effects, such as dizziness and neuropsychiatric disturbances, exhibiting marked concentration dependence. Consequently, conventional fixed-dose regimens often fail to achieve an optimal balance between therapeutic benefit and safety risk. To address this challenge, this article proposes an individualized dosing strategy. Centered on therapeutic drug monitoring (TDM) as a core tool, this approach defines patient-specific individualized target concentration by quantifying actual drug exposure. It proactively manages cytochrome P450 3A4/5 (CYP3A4/5)-mediated drug-drug interactions (DDIs), particularly the alterations in PER exposure induced by potent enzyme inducers, and implements prospective dose adjustments accordingly. Furthermore, it incorporates pharmacogenetic information, such as the CYP3A5*3 polymorphism, as an intrinsic stratification criterion to refine initial dose selection. By synergistically integrating these three dimensions, TDM-guided exposure optimization, DDI-aware dosing, and genotype-informed initiation, this strategy not only enables tailored dosing for vulnerable populations (including children, pregnant women, and patients with renal impairment) but also has the potential to improve overall clinical outcomes, maximizes therapeutic benefit, minimizes safety risks, and enhances the efficiency of healthcare resource utilization.
This study aims to conduct a real-world analysis of blinatumomab-associated neurological adverse events (NAEs) in pediatric patients with B-cell acute lymphoblastic leukemia (B-ALL) to comprehensively elucidate its safety profile. A retrospective analysis was conducted in children with B-ALL who were treated at hematology medical ward of our institution from January 2024 to December 2025. Document the occurrence of all NAEs during the dosing cycle of blinatumomab, including the time of occurrence, cycle of appearance, severity, management, and outcome. There were 13 individuals with an average age of 10.08 ± 4.23 years experienced a total of 18 NAEs among all the 60 B-ALL patients. These NAEs primarily manifest as headache, dizziness, tremor, delirium, status epilepticus, and cerebral herniation. Most NAEs occur during the first cycle of medication (77.78
Introduction: Sirolimus, also known as rapamycin, is an mTOR receptor inhibitor that suppresses cell proliferation and angiogenesis, demonstrating efficacy against multiple types of vascular anomalies. However, sub-therapeutic concentrations (below effective levels) and supra-therapeutic concentrations (leading to adverse reactions) of sirolimus may both negatively impact patient treatment outcomes. This study aimed to establish optimal models to predict the risk of sirolimus exposure using machine learning, ensure that sirolimus blood concentrations remain within the therapeutic range, and thus enhance the efficacy and safety of sirolimus therapy for children with vascular anomalies. Methods: We retrospectively analyzed 134 sirolimus therapeutic drug monitoring (TDM) measurements from 49 patients. Data were randomly split into training (80%) and testing (20%) sets, with an additional temporal cohort for external validation. Six machine learning models were developed to predict sub-therapeutic and supra-therapeutic risks, and evaluated primarily by the area under the receiver operating characteristic curve (AUROC) and Brier score. The optimal model was interpreted using SHapley Additive exPlanations (SHAP) analysis. Results: The sub-therapeutic risk model included body mass index (BMI), white blood cells (WBC), mean corpuscular hemoglobin (MCH), triglycerides (TG), and total bilirubin (TBIL); while the supra-therapeutic model comprised height, platelet count (PLT), alanine aminotransferase (ALT), high-density lipoprotein cholesterol (HDL), and total cholesterol (TC). The multilayer perceptron (MLP) and extreme gradient boosting (XGB) models showed optimal performance for sub-therapeutic (AUROC = 0.646, Brier = 0.190) and supra-therapeutic (AUROC = 0.825, Brier = 0.143) risk prediction, respectively, with consistent results in temporal validation (AUROC: 0.678, Brier = 0.190 and AUROC: 0.767, Brier = 0.190). Conclusion: This study is the first to use machine learning models to predict the risk of sub-or supra-therapeutic sirolimus concentrations in vascular anomalies children. By enabling personalized exposure risk prediction, the dosing accuracy of sirolimus for the treatment of children with vascular anomalies can be optimized, thereby enhancing effectiveness and safety.
Background:This study sought to define the therapeutic drug monitoring (TDM) reference range and assess the efficacy-safety profile along with its determinants for levetiracetam (LEV) in Chinese children with epilepsy. Methods:We conducted a retrospective study (2021-2023) at Children's Hospital of Nanjing Medical University in children with epilepsy taking LEV therapy with routine TDM. The observational LEV reference range was defined by the generalized additive models for location, scale, and shape (GAMLSS) analysis. A linear mixed-effects model identified concentration determinants. Efficacy was assessed via propensity score matching (PSM)-adjusted logistic regression, time-to-failure via Kaplan-Meier/Cox regression (monotherapy), and adverse events (AEs) temporal patterns via Weibull distribution analysis. Results:This study (n = 1,174) proposed an observational LEV reference range of 2.82-24.37 µg/mL based on the 2.5th-97.5th percentile distribution. Predictors of LEV levels included age, body weight, oxcarbazepine (OXC)/topiramate use, and developmental delay. OXC lowered concentration-to-dose (C 0/D) (β = -0.1824, P = 0.0012). The 12-month response rate was 81.01% (90.89% monotherapy vs 70.78% polytherapy). Concentration-response correlation was significant only in focal epilepsy. Protective factors for response were female sex, generalized epilepsy, and longer treatment; risk factors were polytherapy and infectious etiology. Comorbid attention deficit and hyperactive disorder improved, but developmental delay did not affect, response. Neuropsychiatric AEs were most frequent (median onset: 196.5 days); gastrointestinal and systemic reactions showed early failure patterns. Conclusion:This real-world study confirmed the efficacy and safety of LEV in Chinese children with epilepsy and revealed relevant drug interactions. By proposing an observational LEV reference range (2.82-24.37 µg/mL), it provides a critical evidence base for TDM and guides the personalized treatment.
Objective: This study aimed to characterize the population exposure, efficacy, and safety profiles of oxcarbazepine (OXC) in Chinese children with epilepsy using real-world data, define its optimal therapeutic range, and inform individualized therapy. Methods: This single-center retrospective cohort study included pediatric patients (<18 years) who received OXC therapy between September 2021 and August 2024, with follow-up continuing until February 2025. The concentration of the active metabolite 10,11-dihydro-10-hydroxycarbamazepine (MHD) in plasma was monitored. A mixed-effects model identified factors influencing MHD exposure. Logistic regression and Cox proportional hazards models were used to analyze the concentration–efficacy relationship, while Kaplan–Meier and time-to-onset analyses were performed to characterize adverse events. Results: Among 824 included patients (1976 concentration samples), body weight, age, treatment duration, and epilepsy type significantly influenced MHD’s exposure levels. The 12-month overall response rate was higher in monotherapy than add-on therapy (82.9% vs. 60.4%). A plasma MHD concentration ≥ 10 μg/mL was identified as a critical “risk transition point” for treatment failure (PSM-adjusted OR = 2.42, p < 0.001). Multivariate logistic analysis confirmed higher concentrations, specific etiologies, and polytherapy as risk factors for inefficacy. Cox regression further revealed that concentrations ≥ 10 μg/mL and specific etiologies were predictors of reduced long-term treatment persistence. Adverse events occurred in 30.5% of patients; for most, the risk did not change over time. Conclusions: This study tentatively proposed a therapeutic reference range (3.0–20.0 µg/mL) of MHD for Chinese children with epilepsy and identified a concentration ≥ 10 μg/mL as a “risk transition point”. The findings provide practical, evidence-based insights for tailoring OXC therapy and managing potential risks.
A rapid isocratic LC-MS/MS method for quantifying busulfan in human plasma was developed and validated. Plasma samples were processed by protein precipitation with acetonitrile using busulfan-d8 as internal standard. Separation...
ETHNOPHARMACOLOGICAL RELEVANCE:Salvia miltiorrhiza Bunge (SM), a traditional medicinal herb, demonstrates potential in treating pulmonary fibrosis (PF). Although preclinical studies suggest anti-fibrotic properties, its mechanisms remain unclear. This study elucidates the efficacy and molecular pathways of SM in pulmonary fibrosis. MATERIALS AND METHODS:A rodent model of pulmonary fibrosis and an in vitro lung fibroblast system were established. RNA sequencing and gene interference were used to investigate the core mechanism of SM action. RESULTS:We found that SM remarkably alleviated pulmonary fibrosis by reducing pulmonary edema and inflammation in PF rats. SM inhibited TGF-β1-induced fibroblast activation and collagen formation. Mechanistically, SM inhibited TGF-β1-induced Smad2/3 signaling. RNA-seq analysis revealed that SM enhanced mitophagy, thereby preserving mitochondrial membrane potential, a process implicated in fibroblast activation. Moreover, we observed that SM activated PINK1/parkin signaling in cultured fibroblasts and in fibroblasts isolated from fibrotic lungs. SM promoted PINK1 spot formation and increased the mitochondrial LC3BII/I ratio. Furthermore, we found that PINK1 knockdown or AKT inhibition weakens the anti-activating effect in fibroblasts. CONCLUSIONS:Taken together, our results showed that SM could alleviate pulmonary fibrosis. SM promotes mitophagy to reduce mitochondrial dysfunction, thereby inhibiting fibroblast activation. These effects of SM may depend on the regulation of AKT/PINK1 signaling. Taken together, we suggest that SM is a substitution therapy for pulmonary fibrosis with a protective effect on mitochondria.
Background:Pulmonary fibrosis (PF) remains a devastating disease with limited therapeutic options. Astragaloside IV (AS-IV), a natural compound from Astragalus mongholicus (AM), has shown promise as a possible treatment for fibrosis. However, a systematic evaluation of its therapeutic efficacy and underlying mechanisms is lacking. This meta-analysis synthesizes preclinical evidence to assess the therapeutic potential of AS-IV in PF. Methods:Preclinical literature published before 16 August 2024, was systematically retrieved and screened across eight major databases, including PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wan Fang Data Knowledge Service Platforms (Wanfang), China Science and Technology Journal Database (CQVIP), and China Biological Medicine Database (CBM). The risk of bias was assessed using the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) tool, and meta-analysis was conducted using STATA 18.0. The underlying mechanisms were also summarized. Results:This systematic review and meta-analysis encompassed 23 in vivo animal studies comprising a total of 518 animals. The methodological quality scores of the included studies ranged from 3 to 6 points. The overall analysis demonstrated that AS-IV significantly reduced key indicators of PF in animal models, including PF score [SMD = -2.56, 95% CI (-3.47, -1.65), P < 0.01, I 2 = 72.6%]; pulmonary inflammation scores [SMD = -2.18, 95% CI (-3.09, -1.27), P < 0.01, I 2 = 70.2%]; hydroxyproline (HYP) content [SMD = -4.31, 95% CI (-5.67, -2.95), P < 0.01, I 2 = 83.1%]; lung index [SMD = -3.43, 95% CI (-4.75, -2.10), P < 0.01, I 2 = 79.5%]; and α-smooth muscle actin (α-SMA) levels [SMD = -4.79, 95% CI (-6.01, -3.56), P < 0.01, I 2 = 55.3%]. Sensitivity analyses confirmed the robustness of these results. However, the asymmetry observed in the funnel plot suggests potential publication bias. Further analysis revealed that AS-IV modulates key biomarkers involved in the epithelial-mesenchymal transition (EMT) process and mitigates extracellular matrix (ECM) remodeling. Additionally, AS-IV reduces the levels of inflammatory markers and oxidative stress indicators, thereby exerting a significant intervention in PF. Conclusion:This meta-analysis demonstrates that AS-IV consistently ameliorates BLM-induced PF through multiple mechanisms, including inhibition of EMT, ECM remodeling, inflammation, and oxidative stress. These findings support further investigation of AS-IV as a multi-target therapeutic agent for PF. Systematic Review Registration:identifier CRD42024604432.
Omadacycline, a third-generation tetracycline antibiotic, exhibits time-dependent pharmacokinetics. The ratio of the 24-hour area under the concentration-time curve to minimum inhibitory concentration (AUC0-24/MIC) serves as the primary pharmacokinetic/pharmacodynamic (PK/PD) index for omadacycline, demonstrating strong correlation with therapeutic efficacy, particularly in critically ill patient populations. To facilitate routine therapeutic drug monitoring (TDM) in clinical practice, a high-performance liquid chromatography - tandem mass spectrometry (HPLC-MS/MS) method was developed for quantification of omadacycline in human plasma. An Agilent 1260 series liquid chromatograph and an API 4000 triple tandem quadrupole mass spectrometer were used for the determination of omadacycline and endocannabinoids. The separation was performed on a Phenomenex KINETEX XB-C18 column (2.6 μm, 3 × 50 mm) with 0.1% formic acid-water and pure acetonitrile as the mobile phases. The LC-MS/MS separation was carried out using a gradient elution procedure at a flow rate of 0.4 mL/ min, and the total run time was 5 min. An electrospray ionization (ESI) was selected, and the detection ions of omadacycline and the internal standard (fexofenadine-d6) were determined by mass spectrometry scanning with multiple reaction monitoring (MRM) in positive ion mode as follows: m/z 557.4→453.4 and m/z 508.4→472.8, respectively. The established linear range (20-2000 ng/mL) effectively covers the plasma concentration range encountered in > 98% of clinical samples, making it suitable for routine therapeutic drug monitoring. The method demonstrated acceptable selectivity, recovery, and matrix effect. The results of intra-day precision and inter-day precision show that the relative standard deviation (RSD) is less than 10%, while the relative error (RE) is within ± 10.00%. In this study, we developed and validated a simple, sensitive and accurate method to quantify the concentration of omadacycline in human plasma using LC-MS/MS. This offers essential technical support for the rational clinical application of omadacycline.
To improve a pediatric mHealth app for patient counselling, we developed a multi-dimensional evaluation method assessing caregivers' feedback via a cross-sectional survey. Using random questionnaires at a children's hospital outpatient department (967 valid: 478 pre-upgrade, 489 post-upgrade), we evaluated the app across five dimensions (transmission, accuracy, accessibility, completeness, experience). Validity was excellent (I-CVI/S-CVI=1.000), reliability acceptable (ICC 0.806-0.869), with no significant demographic differences between groups (p>0.826). Pre-upgrade, transmission, accuracy, accessibility, and completeness scored >3.50, but experience scored <2.50. All caregivers valued accuracy but reported poor experience. Those over 50 struggled with transmission/accessibility; caregivers <29 and >50 were dissatisfied with completeness. Post-upgrade significantly improved completeness across all ages. The revised app demonstrates excellent accuracy and satisfactory completeness, but requires time for adaptation among caregivers over 50 to transmission/accessibility, and still needs substantial user experience improvements. This multi-dimensional evaluation effectively identified targeted enhancements and ongoing challenges.
The abuse of etomidate (ETM) in e-cigarettes and cigarettes has become a growing public health concern, creating an urgent need for sensitive detection methods in novel environmental matrices (NEMs) such as e-cigarette liquids, cigarette butts, and smoke. This study develops a controlled substance release simulator (RS) to generate and collect smoke samples, coupled with ultra-performance liquid chromatography-high-resolution mass spectrometry (UPLC-HRMS) for the detection and quantification of ETM in NEMs. The method was rigorously validated, demonstrating high sensitivity with limits of detection (LOD) of 0.4 ng/mL for cigarette butts, 0.125 ng/mL for e-cigarette liquids, and 0.5 ng/mL for smoke adsorption pads (SAPs), with a universal lower limit of quantification (LOQ) of 0.5 ng/mL. It also showed excellent linearity (0.5-50 ng/mL, R-2 > 0.99), precision, and accuracy. When applied to authentic seized samples, the method successfully quantified ETM and detected its analog, metomidate (MTM), thereby offering a robust and superior tool for on-site forensic investigations compared to conventional techniques
Thiopurines, a class of antimetabolites widely used in patients with inflammatory bowel disease (IBD) and acute lymphoblastic leukemia (ALL), are associated with two predominant adverse effects: delayed myelotoxicity and hepatotoxicity. The erythrocyte-based active metabolites 6-thioguanine nucleotides (6-TGN) and 6-methylmercaptopurine nucleotides (6-MMPN) serve as biomarkers reflecting systemic drug exposure and predicting both therapeutic efficacy and adverse reactions. In this study, we successfully developed and validated a rapid, sensitive, and accurate liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) analytical method for simultaneous quantification of erythrocyte 6-TG and 6-MMPD concentrations. During method development and validation, we focused on addressing the following five key challenges currently of significant interest in the field: 1) Erythrocytes proved superior to whole blood as biological matrix; 2) Perchloric acid was essential in sample pretreatment; 3) Dual mobile phase additives (HCOOH+NH4Ac) enhanced chromatographic peak shape and detection sensitivity; 4) Incomplete hydrolysis of 6-TGN and 6-MMPN occurred with heating durations < 60 min; 5) The linear correlation coefficient of the 6-MMPD (6-MMP derivative, 4-amino-5-(methylthio)carbonyl imidazole) standard curve reflected the stable conversion efficiency of 6-MMP. The method exhibited excellent linearity over the concentration ranges of 0.06-50 μmol/L for 6-TG (r = 0.9906) and 0.18-150 μmol/L for 6-MMPD (r = 0.9914). Selectivity, carry-over, intra- and inter-batch accuracy and precision, reproducibility, recovery, matrix effect, and stability all complied with the acceptance criteria outlined in the US Food and Drug Administration (FDA) Bioanalytical Method Validation Guidance (2018). The validated method was successfully employed to quantify 6-TG and 6-MMPD in samples obtained from 20 patients with IBD or ALL.
Background:The package insert is a key reference and legal basis for clinical medication. However, in the field of rare diseases, advances in diagnosis and treatment often outpace updates to drug labels, resulting in widespread off-label drug use-a practice that is particularly common and often unavoidable in pediatric populations. Inappropriate off-label use, however, carries significant clinical and safety risks. Methods:Under the guidance of the Rare Disease Expert Committee of the Guangdong Pharmaceutical Association, a multidisciplinary panel of experts from clinical medicine, pharmacy, and related specialties developed the "Expert consensus on the off-label use of drugs for pediatric rare diseases in China (2025 edition)". The consensus integrates available evidence, clinical experience, evidence quality, and medication safety profiles, and was finalized after several rounds of rigorous iterative review. Results:The consensus presents 73 recommendations on off-label drug use across 21 rare diseases, organized in a tabular format for clarity and ease of reference. Conclusions:This consensus aims to standardize the management of off-label drug use in pediatric rare diseases. It supports medical institutions in developing off-label drug formularies, promotes rational drug use, and helps address the diagnostic and therapeutic needs of pediatric rare disease patients. Furthermore, it contributes to the establishment of a structured evaluation and management framework for off-label drug use in this clinical context.
When discussing childhood epilepsy and children's serum vitamin D status together, the matter becomes complex and intriguing. A long-standing question has been whether there is a causal link between epilepsy itself and the serum vitamin D status: does vitamin D deficiency lead to seizures, or do seizures occur alongside or result in vitamin D deficiency, or is the deficiency caused by anti-seizure medication therapy? Clarifying these questions would significantly enhance our understanding of the relationship between them and improve the treatment and management for childhood epilepsy. This narrative review summarized existing literature on vitamin D and pediatric epilepsy and collected those clinical and non-clinical researches in this field to see if sufficient evidence has accumulated to address these questions. Current evidence revealed that children with epilepsy experienced higher rates of vitamin D deficiency, but whether this stems from the condition itself or its treatment remains uncertain. Both clinical and non-clinical studies suggested vitamin D may help control seizures, but its effective dosing and treatment duration need rigorous clinical validation. This clinical situation indicates that continued attention is needed on this important clinical issue concerning children's health, as well as more efforts and attempts to ultimately clarify these matters.
Our randomized, placebo-controlled trial showed resistant starch (RS), a type of prebiotic, has therapeutic effects in metabolic dysfunction-associated steatotic liver disease (MASLD). Here, we observed its heterogeneous efficacy, where 30% of participants exhibited limited benefits, which was replicated in a multi-center trial (ChiCTR2300074588). Multi-omics analysis and fecal microbiota transplantation identified baseline microbiota as a dominant contributor of response. Further population stratification and network analysis combined with in vitro and in vivo experiments revealed Prevotella as the key cause of low response by inhibiting RS-degrading bacteria, thereby impairing RS utilization. Conversely, Bifidobacterium pseudocatenulatum RRP01, a strain isolated from our cohort, restored RS degradation and improved Prevotella-attenuated RS response. Furthermore, we developed a predictive model integrating baseline microbial and clinical features (area under the curve [AUC] = 0.74-0.87), enabling stratification for personalized interventions. Our study indicates that gut microbiota determines the heterogeneity in RS efficacy and offers possibilities for novel microbiota-oriented precision therapeutics for MASLD.
A-kinase anchoring protein 79/150 (AKAP79/150) is a crucial scaffolding protein that positions various proteins at specific synaptic sites to modulate excitatory synaptic intensity. As our understanding of AKAP79/150's biology deepens, along with its significant role in the pathophysiology of various human disorders, there is growing evidence that reveals new opportunities for therapeutic interventions. In this review, we examine the fundamental structure and primary functions of AKAP79/150, emphasizing its pathophysiological mechanisms in different nervous system disorders, particularly inflammatory pain, epilepsy, depression, and Alzheimer's disease. We also discuss its potential therapeutic implications for patients suffering from these conditions.