共找到 20 条结果
Creatine supplementation has demonstrated ergogenic and anabolic effects in healthy and clinical populations. However, its potential therapeutic role in individuals with chronic musculoskeletal pain treated in rheumatological contexts remains unclear. The aim was to evaluate the efficacy and safety of creatine supplementation on pain, physical function/disability, quality of life, muscle strength, skeletal muscle mass, and inflammatory markers in people with chronic musculoskeletal pain usually treated from the rheumatological field. A systematic review was conducted following PRISMA guidelines. Searches were performed in MEDLINE, Web of Science, CINAHL, Scopus, and EMBASE up to July 2026. Eligible studies were randomized or nonrandomized clinical trials that provided creatine supplementation alone or in combination with exercise as a treatment compared to a control or placebo group. Eight studies (n = 189) were included, encompassing fibromyalgia, osteoarthritis, rheumatoid arthritis, and juvenile idiopathic arthritis. Creatine dosages varied from chronic low-dose to loading protocols (20 g/d, 2-5 g/d). Combined creatine plus resistance training may improve strength, skeletal muscle mass, and quality of life beyond exercise alone in osteoarthritis. Trials on fibromyalgia suggest an increase in muscle strength, but inconsistent effects on pain. Rheumatoid arthritis studies suggest gains in skeletal muscle mass and, in pilot studies, reduced disease activity. No major adverse events were reported. In conclusion, creatine supplementation alone may be insufficient to obtain clinical benefits, while combined with resistance exercise it could offer potential benefits for muscle strength, skeletal muscle mass and certain aspects of quality of life in these clinical conditions. However, evidence on pain and inflammation remains limited; Furthermore, the response across different clinical conditions is heterogeneous, highlighting the need for larger, high-quality trials.
To determine whether prior myomectomy reduces hypertensive disorders of pregnancy (HDP) risk in women with fibroids, and whether fibroid location modifies this risk. Retrospective propensity score-matched cohort study using TriNetX, a federated health record network spanning over 100 US healthcare organizations. Women aged 18-55 years attending a prenatal visit were assigned to three groups: fibroids with prior myomectomy; fibroids without myomectomy; and no fibroids (reference). Groups were matched 1: 1 on age, race/ethnicity, BMI, chronic hypertension, pregestational diabetes, tobacco use, and prior assisted reproductive technology. Gestational hypertension, preeclampsia, eclampsia, and superimposed preeclampsia within one year of the prenatal visit, reported as risk ratios (RR) with 95% confidence intervals. A secondary analysis examined HDP risk by fibroid location. After matching, women with fibroids without myomectomy had significantly increased risk of overall HDP (RR 1.21, 95% CI 1.17-1.25), gestational hypertension (RR 1.29, 95% CI 1.22-1.36), preeclampsia (RR 1.31, 95% CI 1.24-1.39), superimposed preeclampsia (RR 1.25, 95% CI 1.12-1.39), and eclampsia (RR 1.38, 95% CI 1.05-1.80) versus reference. Prior myomectomy similarly conferred elevated overall HDP risk (RR 1.24, 95% CI 1.12-1.37). No significant differences were observed between myomectomy and no-myomectomy groups. HDP risk was elevated across all fibroid locations, including subserosal fibroids (overall HDP RR 1.47, 95% CI 1.32-1.65). Uterine fibroids are associated with increased HDP risk regardless of prior myomectomy or fibroid location, suggesting fibroids may represent a marker of systemic vascular dysfunction. Fibroid status should be incorporated into preconception and prenatal HDP risk stratification.
Microvascular hemodynamic abnormalities are closely implicated in the onset and progression of many diseases, and often precede overt clinical symptoms, highlighting the importance of their early and quantitative assessment. However, existing approaches, typified by ultrasound localization microscopy (ULM), are constrained by the need for contrast agents and prolonged data acquisition time, restricting their applicability in special populations, including pregnant women and infants. To address this challenge, we propose a novel blood flow imaging framework, CFREE-uPIV, based on mean-shift theory and ultrasound speckle tracking. By constructing a high-resolution speckle field that characterizes the motion of blood-scattering particles and tracking speckle dynamics across consecutive temporal frames, CFREE-uPIV generates high-resolution vector flow fields that faithfully capture multiscale blood flow velocity, one of the most important hemodynamic parameters, without contrast enhancement. In vivo experiments in rats demonstrate that CFREE-uPIV effectively enhances the resolution of contrast-free ultrasound imaging (∼40 μm) and enables rapid and accurate vector flow estimation. Further validation in a hypoxic-ischaemic encephalopathy model underscores its clinical potential for detecting pathological blood flow alterations. Collectively, this study provides a novel approach for the rapid, contrast-free assessment of microvascular hemodynamics.
Early detection of alcohol use disorder (AUD) amongst people admitted to general hospitals offers an opportunity for early intervention and accesses to evidence-based care. However, current operational models for the management of AUD in these settings are poorly defined, limiting the ability to assess their impact on individual patient outcomes, treatment effectiveness, or healthcare system efficiency. This scoping review aims to identify and characterize existing models of AUD management within general hospitals. A scoping review approach was adopted, including relevant peer-reviewed publications between 1990 and 2025. Studies needed to report on ≥2 care components (systematic screening, brief interventions, medically assisted alcohol withdrawal, relapse prevention initiation, psychosocial interventions, transition to community, provision of training) to be included. Screening and data extraction were performed independently by at least reviewers. Fifty-one (n = 51) records were included, and four distinct models of care were identified (consultation liaison; screening, brief intervention, and referral to treatment; protocol implementation; supported diversion). Models varied in their clinical purpose, target population, and care delivery focus. Within each model, differences in aims, context, and implementation resulted in substantial heterogeneity. Consultation liaison models provided the most multifaceted care, with a specialist team providing clinical leadership, access to evidence-based interventions, transition to community services, and training of the wider workforce, but rarely described any wider systematic screening for AUD. A consistent observation across all identified models was the limited interface with mental health care, representing a critical gap in current AUD management within general hospitals.
First-line treatment of gastric cancer is evolving with the integration of immune checkpoint inhibitors (ICIs) and targeted agents, complicating biomarker stratification. Claudin 18.2 (CLDN18.2) is an established target for zolbetuximab; however, immunohistochemistry (IHC) is limited by tissue requirements, cost, and turnaround time. Artificial intelligence (AI) analysis of hematoxylin and eosin (H&E)-stained slides may provide a scalable alternative. We developed and validated an AI model to predict CLDN18.2 expression from H&E slides and evaluated its clinical utility integrated with AI-derived immune phenotyping. This retrospective study included three independent cohorts of patients with gastric cancer. The development cohort comprised 622 patients (497 for training and 125 for tuning). The internal validation cohort included 378 patients treated with first-line nivolumab plus chemotherapy or chemotherapy alone. The external validation cohort included 98 patients from diverse ethnic backgrounds. Whole-slide H&E-stained images were analyzed using a Vision Transformer-based AI model to predict CLDN18.2 expression. A separate AI model classified the immune microenvironment as inflamed or noninflamed. Primary outcomes were predictive performance metrics, including area under the receiver operating characteristic curve (AUROC). Secondary outcomes included progression-free survival (PFS) and overall survival (OS), stratified by AI-predicted CLDN18.2 status and immune phenotype. CLDN18.2 positivity by IHC was 42.9% (development), 36.8% (internal validation), and 25.5% (external validation). The AI model yielded AUROC values of 0.752 (internal validation) and 0.856 (external validation). In the internal validation cohort, patients with AI-predicted CLDN18.2-negative/inflamed tumors exhibited improved outcomes with nivolumab plus chemotherapy versus chemotherapy alone [PFS: hazard ratio (HR) 0.35, 95% confidence interval (CI) 0.15-0.82; OS: HR 0.40, 95% CI 0.18-0.89]. Patients with CLDN18.2-positive/noninflamed tumors showed no benefit from nivolumab plus chemotherapy. An AI model using routine histology predicted CLDN18.2 expression and immune phenotype in gastric cancer, identifying subgroups with differential benefit from ICI-based chemotherapy.
Sepsis-induced acute lung injury (ALI) is associated with increased morbidity and mortality rates in the intensive care unit. Transcription factor E3(TFE3) is reported to drive inflammation and Golgi stress response in some pathological conditions. However, the functions and regulatory mechanisms of TFE3 in ALI have not been elucidated. This study demonstrated that lipopolysaccharide (LPS)-induced TFE3 expression and nuclear translocation promoted Golgi stress response and inflammatory cytokine upregulation and exacerbated septic lung injury in vivo and in vitro. The knockdown or knockout of Tfe3 alleviated ALI by downregulating Golgi stress response, inflammatory cytokines, and reactive oxygen species. Meanwhile, the knockout or knockdown of Hmox1 promoted TFE3 nuclear translocation, dysregulating the expression of Golgi stress response-related proteins and exacerbating sepsis induced ALI in vivo and in vitro. Thus, TFE3 exacerbates inflammation, apoptosis, and oxidative stress and induces Golgi stress response in sepsis-induced ALI. Additionally, HO-1 exerted protective effects against ALI by downregulating TFE3 expression and nuclear translocation and suppressing Golgi stress response. The regulatory mechanism of HO-1 in the TFE3/Golgi stress response signaling pathway can be a potential therapeutic target for ALI.
Children with congenital heart disease (CHD) experience neurodevelopmental challenges, arising in part from altered brain maturation beginning in utero. There are currently no prenatal interventions to mitigate this risk. Foetal CHD is associated with alterations in maternal blood pressure (BP), for which therapies are available, so we investigated associations between maternal BP, foetal cerebral haemodynamics, and brain growth in foetuses with and without CHD. Our single-centre retrospective cohort study first analysed maternal BP during pregnancy stratified by foetal CHD (n = 494), other foetal anomalies (n = 769), or no foetal anomalies (n = 111). We then performed a prospective study linking maternal BP with foetal brain MRI and cerebral and umbilical Doppler measures in pregnancies with foetal CHD (n = 97 MRI; 121 Doppler) and those with no foetal anomalies (n = 111 MRI; 86 Doppler). Mothers carrying a foetus with CHD showed a distinct BP profile compared with unaffected controls and non-CHD foetal anomaly pregnancies. In CHD pregnancies, but not in controls, lower maternal diastolic BP was associated with lower cerebrovascular resistance, lower cerebroplacental flow ratio, and an attenuated reduction in foetal cortical surface area in sensorimotor, frontal and temporal cortical regions. Lower maternal diastolic BP may reflect adaptive maternal-foetal circulatory coupling that enhances foetal cerebral perfusion and mitigates cortical growth impairment in CHD. We observe a link between maternal haemodynamics and foetal brain maturation in CHD, warranting further exploration in interventional studies. Supported by the NINDS (R01NS114087, K23NS101120), NIBIB (R01EB031170), NHLBI (K08HL157653), AAN Clinical Research Training Fellowship, BBRF Young Investigator Awards, and the Farb Family Fund.
Interhospital transfers are essential to ensure access to appropriate levels of care, yet many transfers are potentially avoidable, leading to unnecessary resource use and patient burden. To determine the association between telemedicine and interhospital transfer rates among patients considered for an interhospital transfer. Five databases were searched from database inception to 20 January 2026. Studies including patients considered for transfer between hospitals, studies comparing telemedicine with usual care, and studies reporting interhospital transfers rates. Two independent reviewers extracted data and assessed risk of bias. The primary outcome was interhospital transfer rate; the secondary outcome was death. Grouping by patient population, clinical indication for transfer, setting, and intervention characteristic was done. Thirty-three studies representing 609 188 patients were included. Given substantial clinical and methodological heterogeneity, a structured narrative synthesis was done. Telemedicine was commonly associated with lower transfer rates in adult (13 of 17 adult only studies) and pediatric (4 of 5 studies) populations, across clinical indication for transfer (medical [9 of 14 studies] versus surgical [6 of 7 studies] versus acute care conditions [7 of 12 studies]), and rural (9 of 16 studies) and urban (9 of 10 studies) settings. Variation in the transfer rate changes was driven by differences in confounder adjustment, comparator definitions, and study design. Telemedicine was associated with lower or unchanged mortality in most studies that assessed mortality (15 of 17 studies). Included studies were mostly observational with risk for confounding, with high heterogeneity driven by variability in study populations, telemedicine models, comparator groups, clinical contexts, and methodological approaches. Telemedicine may support appropriate triage and reduce potentially avoidable interhospital transfers, with no adverse association on mortality, contributing to safe and efficient transfer decision making. None. (PROSPERO: CRD42023493486).
High-risk and relapsed/refractory (R/R) acute lymphoblastic leukemia poses significant therapeutic challenges due to emergent drug resistance and dose-limiting toxicities. Natural products, with their diverse chemical structures and pharmacological activities, provide a promising avenue for multi-target therapies. This review analyzes key natural product classes, such as phenolic compounds, terpenoids, flavonoids, and alkaloids. It aims to elucidate their mechanisms by modulating critical oncogenic pathways to overcome drug resistance, paving the way for rational therapeutic design strategies. A comprehensive literature review was conducted by systematically searching Web of Science, PubMed, and Google Scholar. Search queries combined "acute lymphoblastic leukemia" with various natural product classes, focusing on publications from 2000 to 2025. The analysis synthesized data on molecular mechanisms, pharmacokinetics, safety, and synergistic strategies for combination therapy. The database search yielded 303,464 hits, with 13,839 hits from Web of Science, 14,625 hits from PubMed, and 275,000 hits from Google Scholar. After removal of duplicates, commentary articles, clearly ineligible literature, and records not within the predefined topic range were removed, 280 records were screened. 73 publications were assessed for eligibility, and 53 studies were included in the final synthesis. The studies considered in this review largely focused on chemically characterized natural products and derivatives comprising phenolic compounds, terpenoids, flavonoids, alkaloids, and artemisinin-related compounds. Most evidence was collected from preclinical ALL models and involved modulation of apoptosis, oxidative stress, cell-cycle arrest, autophagy, ferroptosis, and ALL-related signaling pathways. In conclusion, these natural products showed multi-target and pathway-intersecting activities that could improve conventional anti-leukemic treatment and overcome chemoresistance, although clinical translation remains limited by insufficient in vivo validation, insufficient PK/PD characterization, poor bioavailability, and incomplete safety evaluation. Natural products offer a valuable resource for developing novel anti-ALL therapeutics. Their multi-target capability fosters synergistic combinations to combat resistance, highlighting the need for advanced technologies and precision medicine approaches in ALL treatment.
Accurate identification of causal exposures for multimorbidity can benefit the co-prevention and co-management of multiple-related outcomes. This goal can be conceptually addressed within a multi-outcome Mendelian randomization (MR) framework. However, existing multi-outcome MR methods suffer from restrictions on format and availability of data inputs, fail to account for the potential sample overlap, rely on pre-selected independent instrumental variables (IVs), and are unable to account for horizontal pleiotropy. Here, we propose METEOR, a novel MR method that jointly models one exposure and multiple outcomes to identify both shared and outcome-specific causal exposures. METEOR accounts for sample overlap between exposure and outcomes, allows outcomes from different genome-wide association studies (GWAS) datasets, self-adaptively determines IVs from correlated single-nucleotide polymorphisms, and explicitly models horizontal pleiotropy. Using summary statistics, METEOR infers causal effects under a joint-likelihood framework with a scalable, sampling-based algorithm. Simulations show that METEOR presents well-calibrated $P$-values for both global and single-outcome tests, and achieves average power improvements of 55.33% and 56.50% over five existing MR methods in the global and single tests, respectively. In real data applications, METEOR produces the most accurate causal effect estimates in positive control analyses, reduces false positives by 18.75% in negative control analyses, and highlights that controlling BMI could benefit the co-management of multiple cardiovascular diseases (CVDs) and multiple gastrointestinal (GI) diseases, while controlling blood pressure could benefit the co-management of multimorbidity across CVDs and mental disorders (MDs), as well as across GI diseases and MDs.
Mitochondrial DNA (mtDNA) leakage after myocardial ischemia/reperfusion (MI/R) injury activates inflammation and pyroptosis. Although toll-like receptor 4 (TLR4) is a known mediator of MI/R injury, its interplay with mtDNA remains unclear. This study investigates the cardioprotective mechanism of allicin, focusing on its disruption of the TLR4-mtDNA axis. This study aimed to clarify the mechanisms of inflammatory response and pyroptosis in MI/R injury and the therapeutic targets of allicin. The cardioprotective mechanism of allicin was investigated in both in vivo and in vitro MI/R models. In Sprague-Dawley rats, different concentrations of allicin were administered pre-reperfusion. Myocardial injury, cytosolic mtDNA leakage, and activation of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) and nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing 3 (NLRP3)-gasdermin D (GSDMD) pathways were assessed. Network pharmacology combined with molecular dynamics simulation identified TLR4 as a candidate signaling pathway for validation. In H9C2 cells subjected to OGD/R, the role of TLR4 in mtDNA-induced inflammatory response and pyroptosis, and the therapeutic mechanism of allicin, were studied using TLR4 agonist RS09 and inhibitor resatorvid. Myocardial injury markers, cytosolic mtDNA leakage, cGAS-STING and NLRP3-GSDMD pathway activity, and TLR4 expression were measured. In vivo experiments demonstrated that allicin alleviated MI/R injury, suppressed cytosolic mtDNA leakage, and inhibited the cGAS-STING-mediated inflammatory response and the NLRP3-mediated pyroptosis pathways. Subsequent network pharmacology and molecular dynamics simulation identified TLR4 as a potential mediator of these effects. In vitro studies revealed that TLR4 activation promotes mtDNA-dependent inflammation and pyroptosis, which were effectively suppressed by allicin or TLR4 inhibition. TLR4 activation aggravates MI/R injury by promoting mitochondrial damage and cytosolic mtDNA leakage, which activates the pro-inflammatory (cGAS-STING) and pro-pyroptotic (NLRP3-GSDMD) pathways. Allicin protects against MI/R injury by inhibiting TLR4 activation and the subsequent mtDNA-induced pathways, thereby reducing inflammation and pyroptosis.
Non-invasive sweat analysis holds significant promise for personalized health monitoring, yet existing technologies face limitations in mechanical compatibility, signal fidelity, and multimodal detection. Here, a multimodal sensing platform based on a stretchable organic field-effect transistor (OFET) array is presented to address these challenges. The OFET device exhibits excellent stretchability and operational stability, retaining stable electrical performance after 1000 stretching cycles at 30% strain and showing no significant threshold voltage drift under 3 h of bias stress. With extended-gate electrodes functionalized with selective membranes and enzymes, the system detects Na+, K+, Ca2+, glucose, and lactate over physiologically relevant ranges (1 - 100 mM, 1 - 100 mM, 0.1 - 10 mM, 50 - 250 μM, and 5 - 25 mM, respectively), demonstrating high sensitivity, selectivity, and accuracy. Specifically, the ion sensors exhibited detection errors below 4.5%, while the glucose and lactate sensors showed remarkably low response variations with relative standard deviations (RSD) of only 2.16% and 1.18%, respectively. The sensor retains reliable performance in artificial sweat, demonstrating strong resilience to complex biofluid matrices. Integrated with a miniaturized flexible circuit and wireless module, our platform enables real-time data acquisition, processing, and visualization via a mobile application. This work establishes a robust foundation for future wearable diagnostic systems capable of continuous, multi-parameter physiological monitoring.
Oculomotor nerve schwannomas are rare intracranial tumors, particularly in adolescents. When associated with intralesional hemorrhage, they may radiologically mimic completely thrombosed aneurysms of the posterior circulation, creating diagnostic and operative challenges. A 15-year-old girl presented with progressive headache and acute partial left third nerve palsy. MRI demonstrated a heterogeneous hemorrhagic mass in the left interpeduncular cistern closely abutting the superior cerebellar artery-posterior cerebral artery complex. MRA revealed no aneurysm. Two months later, the patient developed complete third nerve palsy, and repeat MRI showed lesion enlargement with subacute hemorrhage. Digital subtraction angiography excluded aneurysm. Resection via an orbitozygomatic approach revealed a lesion arising from the oculomotor nerve without vascular origin. Histopathological analysis confirmed schwannoma (WHO grade 1) with Antoni A and B areas and diffuse S100 positivity. At the 3-month follow-up, third nerve function showed minimal recovery. Hemorrhagic oculomotor schwannoma may closely mimic a completely thrombosed aneurysm in the basilar apex region. Multimodal vascular imaging, recognition of nerve continuity, and radiologic-pathological correlation are essential for accurate diagnosis and operative planning. https://thejns.org/doi/10.3171/CASE26215.
GIM/FP/GP: [Formula: see text] Allerg & Immunol: [Formula: see text] Pulmonology: [Formula: see text].
暂无摘要（点击查看详情）
Uncontrolled hypertension remains a major global health concern and a leading cause of cardiovascular morbidity and mortality. Aldosterone dysregulation plays a critical role in resistant hypertension, and Lorundrostat, a novel aldosterone synthase inhibitor, offers a promising therapeutic approach by directly inhibiting aldosterone production. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of Lorundrostat in adults with uncontrolled hypertension. Comprehensive searches of MEDLINE (PubMed), ScienceDirect, Google Scholar, and Cochrane databases were conducted up to July 2025 following PRISMA guidelines, with the protocol registered on PROSPERO (CRD420251091117). Three randomized controlled trials involving 1,568 participants (1,165 Lorundrostat and 403 placebo) were included, all demonstrating low risk of bias. Pooled analysis revealed that Lorundrostat significantly reduced systolic blood pressure (-8.50 mmHg, 95% CI -11.63 to -5.36, p < 0.00001) and diastolic blood pressure (-3.53 mmHg, 95% CI -5.61 to -1.45, p = 0.0009) compared with placebo, with no heterogeneity observed. However, Lorundrostat was associated with higher risks of hyperkalemia (RR = 5.84, p = 0.01), symptomatic hypotension (RR = 2.98, p = 0.03), serious adverse events (RR = 3.31, p = 0.03), and hyponatremia (RR = 2.03, p = 0.01), though there were no significant differences in moderate or severe adverse events or reduction in kidney function. Publication bias was noted for diastolic blood pressure and selected safety outcomes. In conclusion, Lorundrostat demonstrates clinically meaningful blood pressure reduction in uncontrolled hypertension compared with placebo, but with an increased risk of electrolyte disturbances and hypotension. Cautious use and close monitoring are warranted, and larger, long-term trials are needed to further define its safety and therapeutic role.
Microplastic pollution can affect growth and quality of medicinal plants, yet rapid detection of microplastic stress responses remains underexplored. We treated ginseng with polyethylene microplastics, acquired leaf hyperspectral images (HSI) on day 23, and constructed machine learning models for identifying stress levels and predicting physiological indicators. Furthermore, the applicability of successive projections algorithm (SPA) and competitive adaptive reweighted sampling (CARS) for characteristic wavelength selection was compared. Results showed that polyethylene stress significantly affected the physiological state. The classification models effectively identified microplastic stresses of different concentrations, with the support vector machine (SVM) model performing the best (accuracy of 85.2%). For quantitative prediction, the partial least squares regression (PLSR) model exhibited optimal performance for indicators including chlorophyll (Chl) (RPD = 3.98), soluble sugar (RPD = 2.56) and peroxidase (POD) (RPD = 2.89), and the convolutional neural network performed better in superoxide dismutase (SOD) prediction (aerial RPD = 3.27, underground RPD = 2.65). Leaf spectral data enabled prediction of aerial and underground physiological indicators (RPD = 2.10 to 2.73), indicating that aerial spectral information reflected underground physiological state. Characteristic wavelength selection results showed that SPA had advantages for SOD prediction, while CARS performed better for the remaining seven indicators (RPD >2.0). In conclusion, HSI combined with machine learning models enabled rapid nondestructive identification of microplastic stress responses and prediction of key physiological indicators in ginseng, suggesting quantifiable relationships between aerial spectral data and underground physiological states. This study provides a technical prototype for the growth detection of medicinal plants.
Canada's evolving attitudes toward psychedelic interventions in palliative and end-of-life care reflect a departure from historically prohibitionist policies and an emerging recognition of their therapeutic potential for individuals facing end-of-life distress. This shift parallels international regulatory developments in jurisdictions such as the United States, Australia and parts of Europe, where cautious policy liberalization has signaled growing acceptance of psychedelics within clinical contexts. Canada is also a relevant case because of its formative role in the development of modern palliative care, its contemporary frameworks emphasizing holistic approaches to suffering at the end of life, and its experience with medical assistance in dying, all of which have shaped national conversations about suffering, autonomy, and end-of-life care. Additionally, Canada's distinctive historical approach to drug regulation-marked by federal flexibility, mechanisms for compassionate access, and responsiveness to patient advocacy-combined with rising public demand and incremental provincial changes, may uniquely position the country along a transitional pathway toward clinical integration of psychedelics in palliative care. At the same time, Canadian drug policy remains heterogeneous across substances and provinces, underscoring the political contingency of reform. Within this dynamic landscape, Canada's psychedelic drug policy trajectory aligns with broader international trends toward cautious medicalization and regulated access to psychedelic therapies, while also offering an instructive case for how end-of-life frameworks and federal-provincial governance shape policy development.
A novel ester-functionalized porous polymer adsorbent with a specific surface area of 268.5 m2/g was rationally synthesized via a one-step strategy, which enables selective adsorption of target coumarins relying on multiple intermolecular interactions (hydrogen bonding, hydrophobic effect, π-π stacking, etc.). An integrated online solid-phase extraction-semi-preparative HPLC system was established by coupling this tailor-made adsorbent with semi-preparative HPLC, realizing automated one-step extraction, enrichment and purification of target compounds directly from crude extracts. The loading volume and washing procedures were systematically investigated, and the optimal conditions were determined as follows: a sample loading volume of 3 mL, followed by washing with 0.1% aqueous phosphoric acid at a flow rate of 4.7 mL/min for 2 min. The integrated system exhibited excellent separation performance: praeruptorin A was obtained with 98% purity and a yield of 6.69 mg/g herb, and satisfactory isolation efficiency was achieved for praeruptorin B and praeruptorin C. Impressively, the adsorbent remained stable adsorption performance after 100 reuse cycles, significantly improving the cost-effectiveness of the purification process. This work provides a highly efficient and selective strategy for purifying bioactive coumarins from Peucedanum praeruptorum Dunn, and offers a versatile methodological blueprint and functional adsorbent platform for targeted isolation of high-value components from complex natural matrices, which will promote the research and development of natural product-based drug discovery and herbal medicine.