Therapeutic Drug Monitoring for Lacosamide in Chinese Pediatric Patients with Epilepsy: Focus on Clinical Effectiveness, Tolerability and Drug Interactions.

To investigate the effectiveness and tolerability of lacosamide (LCM) and to select a better reference range for its concentration in plasma for Chinese pediatric patients with epilepsy. In addition, it is necessary to evaluate the potential determinates of LCM concentration. Pediatric epilepsy patients using LCM were retrospective included.

Development and Implementation of a Clinical Decision Support System to Enhance Efficiency and Accuracy in Medication Prescription Review in a Tertiary Care Hospital: A Retrospective Hospital CDSS Register Study.

Background: The integration of Clinical Decision Support Systems (CDSSs) into the prescription review process is expected to mitigate medication errors and increase patient safety. This study aimed to quantify the impact of integrating the CDSS into the prescription review process.

Methods: This retrospective study was conducted by pharmacists at a 3200-bed tertiary hospital in China, leveraging data from the Hospital Information System and CDSS software across two distinct periods: August 2021 to July 2022 (preimplementation) and August 2022 to July 2023 (postimplementation).

Which is the most cost-effective antiseizure medication for initial monotherapy for focal epilepsy?

Objective: An increasing number of antiseizure medications (ASMs) are approved for monotherapy for focal epilepsy, but direct comparisons of the lifetime cost-effectiveness of all existing treatment strategies are lacking. This study aims to compare the cost-effectiveness of new ASMs and traditional ASMs as first-line monotherapy for newly diagnosed focal epilepsy.

Method: We used a Markov model to evaluate the lifetime cost-effectiveness of 10 ASMs in the treatment of focal epilepsy, with lacosamide (LCM) as a control, from the perspective of society in the United States.

Deficiency of histamine H receptors in parvalbumin-positive neurons leads to hyperactivity, impulsivity, and impaired attention.

Attention deficit hyperactivity disorder (ADHD), affecting 4% of the population, is characterized by inattention, hyperactivity, and impulsivity; however, its neurophysiological mechanisms remain unclear. Here, we discovered that deficiency of histamine H receptor (HR) in parvalbumin-positive neurons in substantia nigra pars recticulata (PV) attenuates PV neuronal activity and induces hyperactivity, impulsivity, and inattention in mice. Moreover, decreased HR expression was observed in PV in patients with ADHD symptoms and dopamine-transporter-deficient mice, whose behavioral phenotypes were alleviated by HR agonist treatment.

EvaluationMaster: A GUI Tool for Structure-Based Virtual Screening Evaluation Analysis and Decision-Making Support.

Structure-based virtual screening (SBVS) plays an indispensable role in the early phases of drug discovery, utilizing computational docking techniques to predict interactions between molecules and biological targets. During the SBVS process, selecting appropriate target structures and screening algorithms is crucial, as these choices significantly shape the outcomes. Typically, such selections require researchers to be proficient with multiple algorithms and familiar with evaluation and analysis processes, complicating their tasks.

Cost-effectiveness of clobazam as an adjunctive treatment for refractory epilepsy in China.

Background: Clobazam (CLB) is an effective, safe and well-tolerated adjunctive treatment for refractory epilepsy. However, the cost-effectiveness of CLB in China remains unclear.

Aim: The aim of this study was to evaluate the cost-effectiveness of CLB as an adjunctive therapy for patients with refractory epilepsy in China.

KnoMol: A Knowledge-Enhanced Graph Transformer for Molecular Property Prediction.

Molecular property prediction (MPP) techniques are pivotal in reducing drug development costs by preemptively predicting bioactivity and ADMET properties. Despite the application of numerous deep learning approaches, enhancing the representational capacity of these models remains a significant challenge. This paper presents a novel knowledge-based Transformer framework, KnoMol, designed to improve the understanding of molecular structures.

Discovery of New Phenyltetrazolium Derivatives as Ferroptosis Inhibitors for Treating Ischemic Stroke: An Example Development from Free Radical Scavengers.

Ferroptosis is a promising therapeutic target for injury-related diseases, yet diversity in ferroptosis inhibitors remains limited. In this study, initial structure optimization led us to focus on the bond dissociation enthalpy (BDE) of the N-H bond and the residency time of radical scavengers in a phospholipid bilayer, which may play an important role in ferroptosis inhibition potency. This led to the discovery of compound D1, exhibiting potent ferroptosis inhibition, high radical scavenging, and moderate membrane permeability.

Building a Hospital Pharmacist Workforce by a Diversified and Position-Oriented Learning System.

Background: The role of hospital pharmacists has shifted from primarily ensuring drug supply to providing comprehensive pharmaceutical care. To accommodate this shift, new positions are needed. The traditional training model for hospital pharmacists is no longer sufficient for the evolving demands of pharmaceutical care and these new roles.

HDAC9 Deficiency Upregulates cGMP-dependent Kinase II to Mitigate Neuronal Apoptosis in Ischemic Stroke.

Histone deacetylase 9 (HDAC9) is implicated in ischemic stroke by genome-wide association studies. We conducted a series of experiments using a mouse model of ischemic stroke (middle cerebral artery occlusion followed by reperfusion) to examine the potential role of HDAC9. Briefly, HDAC9 was upregulated in the penumbra.

Discovery of a potent CDKs/FLT3 PROTAC with enhanced differentiation and proliferation inhibition for AML.

AML is an aggressive malignancy of immature myeloid progenitor cells. Discovering effective treatments for AML through cell differentiation and anti-proliferation remains a significant challenge. Building on previous studies on CDK2 PROTACs with differentiation-inducing properties, this research aims to enhance CDKs degradation through structural optimization to facilitate the differentiation and inhibit the proliferation of AML cells.

Discovery of orally bioavailable phenyltetrazolium derivatives for the acute treatment and the secondary prevention of ischemic stroke.

The potential for secondary stroke prevention, which can significantly reduce the risk of recurrent strokes by almost 90%, underscores its critical importance. N-butylphthalide (NBP) has emerged as a promising treatment for acute cerebral ischemia, yet its efficacy for secondary stroke prevention is hindered by inadequate pharmacokinetic properties. This study, driven by a comprehensive structural analysis, the iterative process of structure optimization culminated in the identification of compound B4, which demonstrated exceptional neuroprotective efficacy and remarkable oral exposure and oral bioavailability.

Cell-specific IL-1R1 regulates the regional heterogeneity of microglial displacement of GABAergic synapses and motor learning ability.

Microglia regulate synaptic function in various ways, including the microglial displacement of the surrounding GABAergic synapses, which provides important neuroprotection from certain diseases. However, the physiological role and underlying mechanisms of microglial synaptic displacement remain unclear. In this study, we observed that microglia exhibited heterogeneity during the displacement of GABAergic synapses surrounding neuronal soma in different cortical regions under physiological conditions.

Prevalence and clinical significance of potential drug-drug interactions among lung transplant patients.

Drug-drug interactions (DDIs) are a major but preventable cause of adverse drug reactions. There is insufficient information regarding DDIs in lung transplant recipients. This study aimed to determine the prevalence of potential DDIs (pDDIs) in intensive care unit (ICU) lung transplant recipients, identify the real DDIs and the most frequently implicated medications in this vulnerable population, and determine the risk factors associated with pDDIs.

MOINER: A Novel Multiomics Early Integration Framework for Biomedical Classification and Biomarker Discovery.

In the context of precision medicine, multiomics data integration provides a comprehensive understanding of underlying biological processes and is critical for disease diagnosis and biomarker discovery. One commonly used integration method is early integration through concatenation of multiple dimensionally reduced omics matrices due to its simplicity and ease of implementation. However, this approach is seriously limited by information loss and lack of latent feature interaction.

Application of Northern Goshawk Back-Propagation Artificial Neural Network in the Prediction of Monohydroxycarbazepine Concentration in Patients with Epilepsy.

Introduction: A northern goshawk back-propagation artificial neural network (NGO-BPANN) model was established to predict monohydroxycarbazepine (MHD) concentration in patients with epilepsy.

Methods: The data were collected from 108 Han Chinese patients with epilepsy on oxcarbazepine monotherapy. The results of 14 genotype variates were selected as the input layer in the first BPANN model, and the variables that had a more significant impact on the plasma concentration of MHD were retained.

Initial therapeutic target attainment of perampanel in pediatric patients with epilepsy.

Perampanel is a promising option for the treatment of pediatric epilepsy, but its plasma concentration varies among patients. This retrospective study aimed to investigate the initial target attainment of perampanel plasma concentration in pediatric patients with epilepsy in China. Inpatients admitted from January 2020 to December 2021 in a tertiary hospital were retrospectively included according to pre-set criteria.

Discovery of a potent and selective PARP1 degrader promoting cell cycle arrest via intercepting CDC25C-CDK1 axis for treating triple-negative breast cancer.

PARP1 is a multifaceted component of DNA repair and chromatin remodeling, making it an effective therapeutic target for cancer therapy. The recently reported proteolytic targeting chimera (PROTAC) could effectively degrade PARP1 through the ubiquitin-proteasome pathway, expanding the therapeutic application of PARP1 blocking. In this study, a series of nitrogen heterocyclic PROTACs were designed and synthesized through ternary complex simulation analysis based on our previous work.

SingPro: a knowledge base providing single-cell proteomic data.

Single-cell proteomics (SCP) has emerged as a powerful tool for detecting cellular heterogeneity, offering unprecedented insights into biological mechanisms that are masked in bulk cell populations. With the rapid advancements in AI-based time trajectory analysis and cell subpopulation identification, there exists a pressing need for a database that not only provides SCP raw data but also explicitly describes experimental details and protein expression profiles. However, no such database has been available yet.

Prevalence and influencing factors of probiotic usage among colorectal cancer patients in China: A national database study.

Probiotics have become increasingly popular among cancer patients. However, there is limited data from a real-world setting. This study aims to conduct a retrospective analysis to understand the trend of probiotic prescriptions in Chinese colorectal cancer patients.

Upregulation of HDAC9 in hippocampal neurons mediates depression-like behaviours by inhibiting ANXA2 degradation.

Major depressive disorder (MDD) is a pervasive and devastating mental disease. Broad spectrum histone deacetylase (HDAC) inhibitors are considered to have potential for the treatment of depressive phenotype in mice. However, due to its non-specific inhibition, it has extensive side effects and can not be used in clinical treatment of MDD.

Salvianolic acid B ameliorates neuroinflammation and neuronal injury via blocking NLRP3 inflammasome and promoting SIRT1 in experimental subarachnoid hemorrhage.

The nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-mediated immuno-inflammatory response plays a critical role in exacerbating early brain injury (EBI) after subarachnoid hemorrhage (SAH). Salvianolic acid B (SalB) has previously been shown to suppress neuroinflammatory responses in many disorders. Meanwhile, a previous study has demonstrated that SalB mitigated oxidative damage and neuronal degeneration in a prechiasmatic injection model of SAH.