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Efficacy and Safety of SHR8554 on Postoperative Pain in Subjects with Moderate to Severe Acute Pain Following Orthopedic Surgery: A Multicenter, Randomized, Double-blind, Dose-explored, Active-controlled, Phase II/III Clinical Trial.
Pharmacol Res
January 2025
Department of Anesthesiology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Key Laboratory of Anesthesiology (Shanghai Jiao Tong University), Ministry of Education, Shanghai, China. Electronic address:
Biased µ-opioid receptor (MOR) agonists enhance pain relief by selectively activating G protein-coupled receptor signaling and minimizing β-arrestin-2 activation, resulting in fewer side effects. This multicenter Phase II/III trial evaluated the optimal dosage, efficacy, and safety of SHR8554, a biased MOR agonist, for postoperative pain management following orthopedic surgery. In Phase II, 121 patients were divided into four groups to receive varying patient-controlled analgesia (PCA) doses of SHR8554 or morphine.
View Article and Find Full Text PDFAncient engineers: The role of plateau pika in shaping ecological uniqueness and guiding plant diversity conservation in alpine grasslands.
J Environ Manage
January 2025
State Key Laboratory of Herbage Improvement and Grassland Agro-ecosystems, Key Laboratory of Grassland Livestock Industry Innovation, College of Pastoral Agriculture Science and Technology, Lanzhou University, Lanzhou, 730020, China. Electronic address:
Small burrowing herbivores play a crucial role in maintaining structure and function of grassland ecosystems. To date, our understanding of whether practicing ecological uniqueness can enhance plant diversity conservation under small herbivore disturbances remains limited. Here, we investigate the ecological uniqueness of plant communities, which include habitats disturbed and undisturbed by plateau pikas.
View Article and Find Full Text PDFTracking the optimal watershed landscape pattern for driving pollutant transport: Insights from the integration of mechanistic models and data-driven approaches.
J Environ Manage
January 2025
College of Water Sciences, Beijing Normal University, Beijing, 100875, China.
Identifying landscape patterns conducive to pollutant transport control is of vitally importance for water quality protection. However, it remains unclear which landscape patterns can weaken the transport capacity of pollutants entering water bodies. To fill this gap, this study proposes a new framework.
View Article and Find Full Text PDFCould CGRP mAbs for migraine trigger rheumatoid arthritis? Insights from a case report.
ARP Rheumatol
January 2024
ULS Gaia e Espinho.
Background: Case reports suggest that calcitonin gene-related peptide monoclonal antibodies (CGRP mAbs) may trigger inflammatory flares in patients with autoimmune diseases.
Case Description: A 56-year-old woman with a history of severe migraines, experienced improvement in migraine frequency and intensity after starting fremanezumab 225 mg monthly. However, three months into treatment, she developed symmetric inflammatory polyarthralgias.
Landscape analysis of adverse events and dose intensity for FDA approved oncology small molecules.
Cancer Chemother Pharmacol
January 2025
Clinical Pharmacology and Translational Sciences, Pfizer Worldwide R&D, 10555 Science Center Drive, San Diego, CA, 92121, USA.
As development of new oncology small molecule therapies is focused mainly on molecularly targeted agents, the dose selection paradigm has shifted from the maximum tolerated dose (MTD)-based approach traditionally utilized with cytotoxic drugs towards determining an optimal dose with long-term tolerability while maintaining efficacy. To assess overall tolerability in recently approved oncology small molecules, we surveyed 54 compounds approved by the FDA since March 2017 with respect to dose intensity, dose modifications, and treatment emergent adverse events (TEAEs). Of the 54 new molecular entities surveyed, only 15 were approved at a label dose equal to the MTD (Label Dose = MTD).
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