Dual-attention transformer-based hybrid network for multi-modal medical image segmentation.

Accurate medical image segmentation plays a vital role in clinical practice. Convolutional Neural Network and Transformer are mainstream architectures for this task. However, convolutional neural network lacks the ability of modeling global dependency while Transformer cannot extract local details.

Lymphocyte-Derived Engineered Apoptotic Bodies with Inflammation Regulation and Cartilage Affinity for Osteoarthritis Therapy.

Apoptotic bodies as plentiful extracellular vesicles generated from apoptotic cells play a central role in signal transduction and homeostasis regulation and simultaneously switch death to regeneration to a certain extent. Herein, we designed engineered apoptotic bodies derived from T cells to have the capacity of inflammation regulation and cartilage affinity. The engineered apoptotic bodies as a natural anti-inflammation factor were encapsulated into lubricating hydrogel microspheres to achieve an injectable microsphere complex for the treatment of osteoarthritis (OA).

Hepatic perivascular epithelioid cell tumor: a retrospective analysis of 36 cases.

Background And Aims: Hepatic perivascular epithelioid cell tumor (PEComa) is a rare type of mesenchymal neoplasm and lacks systematic reports. The aim was to analyze the features of hepatic PEComa in order to provide our own experience for diagnosis and management from a single center.

Methods: We retrospectively analyzed clinical data, imaging findings, pathology, treatments and prognosis of 36 patients with hepatic PEComa in the First Affiliated Hospital of Zhengzhou University from January 2016 to September 2023.

Integrated serum metabolomics, 16S rRNA sequencing and bile acid profiling to reveal the potential mechanism of gentiopicroside against nonalcoholic steatohepatitis in lean mice.

Ethnopharmacological Relevance: Lean nonalcoholic steatohepatitis (NASH) poses a serious threat to public health worldwide. Herbs of the genus Gentiana have been used for centuries to treat hepatic disease or have been consumed for hepatic protection efficiency. Gentiopicroside (GPS), the main bioactive component of Gentiana herbs, has been shown to be beneficial for protecting the liver, improving intestinal disorders, modulating bile acid profiles, ameliorating alcoholic hepatosteatosis, and so on.

Identification of the human Cytochrome P450 enzymes (P450s) responsible for metabolizing infigratinib to its pharmacologically active Metabolites, BHS697, and CQM157, and assessment of their in vitro inhibition of P450s and UDP-glucuronosyltransferases (UGTs).

Infigratinib, an oral FGFR inhibitor for advanced cholangiocarcinoma, yielded two active metabolites, BHS697 and CQM157, with similar receptor affinity. Our study characterized P450s that are responsible for the metabolism of infigratinib to its two major active metabolites, BHS697 and CQM157. In vitro inhibition of P450s and UGTs by infigratinib, BHS697 or CQM157 was further investigated.

Impact of CYP2C19, CYP2C9, CYP3A4, and FMO3 Genetic Polymorphisms and Sex on the Pharmacokinetics of Voriconazole after Single and Multiple Doses in Healthy Chinese Subjects.

Voriconazole is the first-line treatment for invasive aspergillosis. Its pharmacokinetics exhibit considerable inter- and intra-individual variability. The purpose of this study was to investigate the effects of CYP2C19, CYP2C9, CYP3A4, and FMO3 genetic polymorphisms and sex on the pharmacokinetics of voriconazole in healthy Chinese adults receiving single-dose and multiple-dose voriconazole, to provide a reference for its clinical individualized treatment.

Physiologically Based Pharmacokinetic Modeling to Investigate the Disease-Drug-Drug Interactions between Voriconazole and Nirmatrelvir/Ritonavir in COVID-19 Patients with CYP2C19 Phenotypes.

Coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis superinfection with cytokine storm is associated with increased mortality. This study aimed to establish a physiologically-based pharmacokinetic (PK) model to investigate the disease-drug-drug interactions between voriconazole and nirmatrelvir/ritonavir in patients with COVID-19 with elevated interleukin-6 (IL-6) levels carrying various CYP2C19 phenotypes. The model was constructed and validated using PK data on voriconazole, ritonavir, and IL-6, and was subsequently verified against clinical data from 78 patients with COVID-19.

Ciprofol is primarily glucuronidated by UGT1A9 and predicted not to cause drug-drug interactions with typical substrates of CYP1A2, CYP2B6, and CYP2C19.

Ciprofol is a novel intravenous anesthetic agent. Its major glucuronide metabolite, M4, is found in plasma and urine. However, the specific isoforms of UDP-glucuronosyltransferases (UGTs) that metabolize ciprofol to M4 remain unknown.

Designing a doctor evaluation index system for an online medical platform based on the information system success model in China.

Objective: In the context of "internet + medical health" and emphasis on evaluation mechanism for medical and health talents in China, we design an evaluation index system for doctors on online medical platforms by synthesizing two patterns of existing online medical platforms, which is the first step to enhance the capabilities of doctors on online medical platforms.

Methods: Based on the doctor evaluation model integrating information systems success model (ISS-DE model) and grounded theory, the evaluation indicators were obtained through expert interviews, offline medical institutions investigation, online platforms investigation, and literature research, and were assigned weights using the analytic hierarchy process (AHP) method. A working group composed of 23 experts was set up to review and determine the competency standards of doctors on the online medical platforms.

Dynamic Stiffening Hydrogel with Instructive Stiffening Timing Modulates Stem Cell Fate In Vitro and Enhances Bone Remodeling In Vivo.

Biomechanical stimuli derived from the extracellular matrix (ECM) extremely tune stem cell fate through 3D and spatiotemporal changes in vivo. The matrix stiffness is a crucial factor during bone tissue development. However, most in vitro models to study the osteogenesis of mesenchymal stem cells (MSCs) are static or stiffening in a 2D environment.

Pan-cancer analysis of the prognostic and immunological role of PAQR4.

Progestin and adipoQ receptor family member 4 (PAQR4) is a protein-coding gene. Recent studies have shown that PAQR4 is related to the development of multiple cancers. However, there is no systematic pan-cancer analysis of this gene.

Freeze-casting osteochondral scaffolds: The presence of a nutrient-permeable film between the bone and cartilage defect reduces cartilage regeneration.

Microfracture treatment that is basically relied on stem cells and growth factors in bone marrow has achieved a certain progress for cartilage repair in clinic. Nevertheless, the neocartilage generated from the microfracture strategy is limited endogenous regeneration and prone to fibrosis due to the influences of cell inflammation and vascular infiltration. To explore the crucial factor for articular cartilage remodeling, here we design a trilaminar osteochondral scaffold with a selective permeable film in middle isolation layer which can prevent stem cells, immune cells, and blood vessels in the bone marrow from invading into the cartilage layer, but allow the nutrients and cytokines to penetrate.

Monoporous Microsphere as a Dynamically Movable Drug Carrier for Osteoporotic Bone Remodeling.

To repair systematically osteoporotic bone defects, it is important to make an effort to both diminish osteoporosis and enhance bone regeneration. Herein, a specifically monoporous microsphere (MPM) carrier encapsulating dosage-sensitive and short half-time parathyroid hormone (PTH) is constructed to tackle the issue. Compared with conventional microsphere carriers involving compact, porous, and mesoporous microspheres, the MPM is desirable to achieve precisely in situ delivery and to minimize topical accumulation.

Development of Physiology Based Pharmacokinetic Model to Predict the Drug Interactions of Voriconazole and Venetoclax.

Purpose: Venetoclax (VEN), an anti-tumor drug that is a substrate of cytochrome P450 3A enzyme (CYP3A4), is used to treat leukemia. Voriconazole (VCZ) is an antifungal medication that inhibits CYP3A4. The goal of this study is to predict the effect of VCZ on VEN exposure.

Integrated polycaprolactone microsphere-based scaffolds with biomimetic hierarchy and tunable vascularization for osteochondral repair.

Osteochondral lesion potentially causes a variety of joint degenerative diseases if it cannot be treated effectively and timely. Microfracture as the conservative surgical choice achieves limited results for the larger defect whereas cartilage patches trigger integrated instability and cartilage fibrosis. To tackle aforementioned issues, here we explore to fabricate an integrated osteochondral scaffold for synergetic regeneration of cartilage and subchondral bone in one system.

Inhibition of cytochrome P450 enzymes and uridine 5'-diphospho-glucuronosyltransferases by vicagrel in human liver microsomes: A prediction of potential drug-drug interactions.

Vicagrel, an antiplatelet drug candidate targeting platelet P2Y receptor and has finished its phase II clinical trial. The inhibition of six major cytochrome P450 enzymes (P450) (CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4) and six UDP-glucuronosyltransferases (UGT) (UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A9, and UGT2B7) by vicagrel was evaluated using pooled human liver microsomes and specific probe substrates. Physiology-based pharmacokinetic (PBPK) simulation was further applied to predict the in vivo drug-drug interaction (DDI) potential between vicagrel and bupropion as well as S-mephenytoin.

Baicalin Enhanced Oral Bioavailability of Sorafenib in Rats by Inducing Intestine Absorption.

Sorafenib (SOR) is an oral, potent, selective, irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) used as the first-line therapy for advanced hepatocellular carcinoma (HCC). Baicalin (BG) is used as adjuvant therapy for hepatitis, which accounts for the leading cause of the development of HCC, and is commonly coadministered with SOR in clinic. The purpose of the current study was to characterize the pharmacokinetic changes of SOR and the potential mechanism when SOR is administered concomitantly with BG in rats for single and multiple doses.

Analyzing Potential Intestinal Transporter Drug-Drug Interactions: Reevaluating Ticagrelor Interaction Studies.

Purpose: Previous studies evaluating ticagrelor drug-drug interactions have not differentiated intestinal versus systemic mechanisms, which we do here.

Methods: Using recently published methodologies from our laboratory to differentiate metabolic- from transporter-mediated drug-drug interactions, a critical evaluation of five published ticagrelor drug-drug interactions was carried out to investigate the purported clinical significance of enzymes and transporters in ticagrelor disposition.

Results: The suggested CYP3A4 inhibitors, ketoconazole and diltiazem, displayed unchanged mean absorption time (MAT) and time of maximum concentration (T) values as was expected, i.

Contributions of UDP-Glucuronosyltransferases to Human Hepatic and Intestinal Metabolism of Ticagrelor and Inhibition of UGTs and Cytochrome P450 Enzymes by Ticagrelor and its Glucuronidated Metabolite.

Ticagrelor is the first reversibly binding, direct-acting, oral P2Y receptor inhibitor. The contribution of UDP-glucuronosyltransferases (UGTs) enzymes to the metabolism of ticagrelor to its glucuronide conjugation, ticagrelor-O-glucuronide, in human liver microsomes (HLM) and human intestinal microsomes (HIM), was well characterized in the current study. The inhibition potential of human major UGTs by ticagrelor and ticagrelor-O-glucuronide was explored.

Estimating leaf area index using unmanned aerial vehicle data: shallow vs. deep machine learning algorithms.

Measuring leaf area index (LAI) is essential for evaluating crop growth and estimating yield, thereby facilitating high-throughput phenotyping of maize (Zea mays). LAI estimation models use multi-source data from unmanned aerial vehicles (UAVs), but using multimodal data to estimate maize LAI, and the effect of tassels and soil background, remain understudied. Our research aims to (1) determine how multimodal data contribute to LAI and propose a framework for estimating LAI based on remote-sensing data, (2) evaluate the robustness and adaptability of an LAI estimation model that uses multimodal data fusion and deep neural networks (DNNs) in single- and whole growth stages, and (3) explore how soil background and maize tasseling affect LAI estimation.

Pharmacokinetics, Urinary Excretion, and Pharmaco-Metabolomic Study of Tebipenem Pivoxil Granules After Single Escalating Oral Dose in Healthy Chinese Volunteers.

Tebipenem pivoxil (TBPM-PI), an oral carbapenem antibiotic, has shown special advantages in pediatric infections and was in urgent need in China. Although pharmacokinetics, urinary excretion, and metabolite information of its active form tebipenem (TBPM) has been reported, ethnic differences may exist among the Chinese and Japanese population. By now, no systematic pharmacokinetics, urinary excretion, metabolites, or safety information has been revealed to the Chinese population.

A physiologically based pharmacokinetic/pharmacodynamic modeling approach for drug-drug interaction evaluation of warfarin enantiomers with sorafenib.

Sorafenib was suggested to cause drug-drug interaction (DDI) with the common anticoagulant, warfarin based on published studies. The inhibition on CYP2C9 enzyme was thought to be the mechanism, but further studies are warranted. Thus, a mechanistic PBPK/PD model for warfarin enantiomers was developed to predict DDI potential with sorafenib, aiming at providing reference for the rational use of both drugs.

Corrigendum: Predicting the Effects of CYP2C19 and Carboxylesterases on Vicagrel, a Novel P2Y12 Antagonist, by Physiologically Based Pharmacokinetic/Pharmacodynamic Modeling Approach.

[This corrects the article DOI: 10.3389/fphar.2020.