BackgroundErector spinae plane block (ESPB) is a novel regional anesthesia technique that is gaining popularity for postoperative pain management. This randomized controlled trial evaluated the effect of ESPB on quality of recovery (QoR) in patients undergoing modified radical mastectomy.MethodsEighty-two female patients undergoing modified radical mastectomy were included. Patients were randomly assigned to receive preoperative ultrasound-guided ESPB with either 0.5% ropivacaine or saline. The primary outcome was QoR, assessed 24 hours postoperatively using the 15-item QoR questionnaire (QoR-15). Secondary outcomes included postoperative pain scores, postoperative cumulative opioid consumption, postanesthesia care unit (PACU) discharge time, postoperative nausea or vomiting and dizziness.ResultsGlobal QoR-15 scores 24 hours postoperatively were significantly higher (indicating better quality) in the ESPB group (median 120, IQR 118–124) compared with the control group (median 110, IQR 108.3–112.8), with a median difference of 10 (95% CI 9 to 12, p<0.001). Compared with the control group, ESPB with ropivacaine reduced pain scores up to 8 hours after surgery, as well as reduced postoperative cumulative opioid consumption and PACU discharge time.ConclusionsA single preoperative injection of ESPB with ropivacaine may improve QoR postoperatively and acute postoperative analgesia in patients undergoing a modified radical mastectomy.Trial registration numberChiCTR-1800019599.
Large parallel gains in the development of both computational resources and sampling methods have now made it possible to simulate dissociation events in ligand− protein complexes with all-atom resolution. Such encouraging progress, together with the inherent spatiotemporal resolution associated with molecular simulations, has left their use for investigating dissociation processes brimming with potential, both in rational drug design, where it can be an invaluable tool for determining the mechanistic driving forces behind dissociation rate constants, and in force-field development, where it can provide a catalog of transient molecular structures with which to refine force fields. Although much progress has been made in making force fields more accurate, reducing their error for transient structures along a transition path could yet prove to be a critical development helping to make kinetic predictions much more accurate. In what follows, we will provide a state-of-the-art compilation of the enhanced sampling methods based on molecular dynamics (MD) simulations used to investigate the kinetics and mechanisms of ligand−protein dissociation processes. Due to the time scales of such processes being slower than what is accessible using straightforward MD simulations, several ingenious schemes are being devised at a rapid rate to overcome this obstacle. Here we provide an up-to-date compendium of such methods and their achievements and shortcomings in extracting mechanistic insight into ligand−protein dissociation. We conclude with a critical and provocative appraisal attempting to answer the title of this Perspective.
Melatonin exhibits antitumour activities in the treatment of many human cancers. In the present study, we aimed to improve the therapeutic potential of melatonin in gastric cancer. Our results confirmed that melatonin dose‐dependently suppressed the proliferation and necrosis, and increased G0/G1 phase arrest, apoptosis, autophagy and endoplasmic reticulum (ER) stress. The Ras‐Raf‐MAPK signalling pathway was activated in cells after melatonin treatment. RNA‐seq was performed and GSEA analysis further confirmed that many down‐regulated genes in melatonin‐treated cells were associated with proliferation. However, GSEA analysis also indicated that many pathways related to metastasis were increased after melatonin treatment. Subsequently, combinatorial treatment was conducted to further investigate the therapeutic outcomes of melatonin. A combination of melatonin and thapsigargin increased the apoptotic rate and G0/G1 cell cycle arrest when compared to treatment with melatonin alone. Melatonin in combination with thapsigargin triggered the increased expression of Bip, LC3‐II, phospho‐Erk1/2 and phospho‐p38 MAPK. In addition, STF‐083010, an IRE1a inhibitor, further exacerbated the decrease in survival rate induced by combinatorial treatment with melatonin and thapsigargin. Collectively, melatonin was effective in gastric cancer treatment by modifying ER stress.
An electrochemically controlled synthesis of multiblock copolymers by alternating the redox states of (salfan)Zr-(O t Bu) 2 (salfan = 1,1′-di(2-tert-butyl-6-N-methylmethylenephenoxy)ferrocene) is reported. Aided by electrochemistry with a glassy carbon working electrode, an in situ potential switch alters the catalyst's oxidation state and its subsequent monomer (Llactide, β-butyrolactone, or cyclohexene oxide) selectivity in one pot. Various multiblock copolymers were prepared, including an ABAB tetrablock copolymer, poly(cyclohexene oxide-b-lactide-bcyclohexene oxide-b-lactide), and an ABC triblock copolymer, poly(hydroxybutyrate-b-cyclohexene oxide-b-lactide). The polymers produced using this technique are similar to those produced via a chemical redox reagent method, displaying moderately narrow dispersities (1.1−1.5) and molecular weights ranging from 7 to 26 kDa.
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