Background and Aim Remimazolam tosilate (RT) is a new short‐acting GABA(A) receptor agonist, having potential to be an effective option for procedural sedation. Here, we aimed to compare the efficacy and safety of RT with propofol in patients undergoing upper gastrointestinal endoscopy. Methods This positive‐controlled, non‐inferiority, phase III trial recruited patients at 17 centers, between September 2017 and November 2017. A total of 384 patients scheduled to undergo upper gastrointestinal endoscopy were randomly assigned to receive RT or propofol. Primary endpoint was the success rate of sedation. Adverse events (AEs) were recorded to evaluate safety. Results The success rate of sedation in the RT group was non‐inferior to that in the propofol group (97.34% vs 100.00%; difference in rate −2.66%, 95% CI −4.96 to −0.36, meeting criteria for non‐inferiority). Patients in the RT group had longer time to adequate sedation (P < 0.0001) but shorter time to fully alert (P < 0.0001) than that in the propofol group. The incidences of hypotension (13.04% vs 42.86%, P < 0.0001), treatment‐related hypotension (0.54% vs 5.82%, P < 0.0001), and respiratory depression (1.09% vs 6.88%, P = 0.0064) were significantly lower in the RT group. AEs were reported in 74 (39.15%) patients in the RT group and 114 (60.32%) patients in the propofol group, with significant difference (P < 0.0001). Conclusion This trial established non‐inferior sedation success rate of RT compared with propofol. RT allows faster recovery from sedation compared with propofol. The safety profile is favorable and appears to be superior to propofol, indicating that it was feasible and well tolerated for patients.
Low back pain (LBP) is a common health problem and many LBP are caused by lumbar disc degeneration (LDD). ADAMTS-4 (a disintegrin and metalloprotease with thrombospondin motifs-4), also known as aggrecanse-1, plays a core role in degeneration of extracellular matrix in LDD. To investigate the association between ADAMTS-4 genetic polymorphism and LDD, we genotyped SNPs in and around ADAMTS-4. We recruited 482 sporadic cases of LDD and 496 healthy controls from Chinese Han population. Five SNPs were selected and phenotyped by the Sequenom MassARRAY system. Allelic, genotypic, and haplotypic association was performed. Rs4233367 (c.1877 C>T), which located in exon of ADAMTS-4 showed significant association with LDD. The T allele conferred a lower risk of LDD with an OR of 0.69 and TT genotype is at nearly one-fifth of the risk compared to CC genotype. Other tested SNPs didn't show significant difference between the case and control groups. The SNP rs4233367 in the exon of ADAMTS-4 gene may be associated with lumbar disc degeneration. Keywords: lumbar disc degeneration (LDD); a disintegrin and metalloprotease with thrombospondin motifs-4 (ADAMTS-4); single nucleotide polymorphism (SNP)
IntroductionDiabetes affects both the peripheral and central nervous systems. The aim of this study was to explore the changes in brain activity in response to thermal stimuli in diabetic patients with and without diabetic peripheral neuropathy (DPN) using functional magnetic resonance imaging (fMRI).MethodsA total of 36 right-handed volunteers were enrolled: eight patients with Type-2 diabetes mellitus and DPN, 13 patients with Type-2 diabetes mellitus lacking DPN (NDPN patients), and 15 healthy volunteers (HV). Blood oxygenation level-dependent baseline scans were performed, first without any stimuli, and then with four sessions of thermal stimuli (0, 10, 34, and 44°C, in a random order) applied to the lateral side of the right lower extremity. There was a 240-s rest interval between each thermal stimulation. Each stimulation session consisted of three cycles of 30 s of stimulation followed by 30 s of rest. After each stimuli session, the participant rated pain and itch perception on a visual analog scale. The fMRI data series were analyzed by using Statistical Parametric Mapping 8 and Data Processing Assistant for Resting-State fMRI.ResultsIn response to temperature stimuli, DPN patients showed stronger activation than HV and NDPN patients, not only in brain areas that participate in somatosensory pathways (right insula, left caudate nucleus, frontal gyrus, and cingulate cortex), but also in the cognition-related cerebral areas (right temporal lobe, left hippocampus, and left fusiform gyrus). Activation of vermis 1–3 was greater in NDPN patients than in HV in response to 0°C stimulation.ConclusionsfMRI may be useful for the early detection of central nervous system impairment caused by DPN. Our results indicate that central nervous system impairment related to diabetic neuropathy may not be limited to motion- and sensation-related cortical regions. Cognition-associated cerebral regions such as the hippocampus and fusiform gyrus are also affected by functional changes caused by DPN. This suggests that fMRI can detect the early stages of cognitive impairment in DPN patients before the symptoms become clinically significant.
For the past century, scientists have developed a variety of methods to evaluate itch and pain in both animal models and human subjects to throw light on some of the most important pathways mediating these unpleasant sensations. Discoveries in the mechanisms underlying itch and pain in both physiological and pathological conditions relied greatly upon these studies and may eventually lead to the discovery of new therapeutics. However, it was a much more complicated job to access itch and pain in animal models than in human subjects due to the subjective nature of these sensations. The results could be contradictory or even misleading when applying different methodologies in animal models, especially under pathological conditions with a mixed sensation of itch and pain. This chapter introduces and evaluates some of the classical and newly designed methodologies to access the sensation of itch and pain in animal models as well as human subjects.
Aluminum nitride nanotubes (AlNNTs) doped by the excess electron, e@AlNNT and M@N-AlNNT (M = Li, Na, K), have been designed and their geometrical, electronic, and nonlinear optical (NLO) properties have been explored theoretically. The results showed that the excess electron narrows the energy gap between HOMO and LUMO values (E) of the doped systems in the range of 3.42-5.37 eV, which is due to a new energy level HOMO formed for the doped excess electron, with higher energy than the original HOMO of AlNNT. Importantly, the doped excess electron considerably increases the first hyperpolarizability (β) from 130 a.u. of the undoped AlNNT to 646 a.u. for e@AlNNT, 2606 a.u. for Li@N-AlNNT, while 1.14 × 10 a.u. for Na@N-AlNNT, and 1.37 × 10 a.u. for K@N-AlNNT. The enormous β values for Na@N-AlNNT and K@N-AlNNT are attributed to the low transition energy. These results demonstrate that AlNNTs are a promising material in high-performance NLO nanomaterials for electronic devices.
Carbamates weaken the luminol-H 2 O 2 chemiluminescence (CL) catalyzed by sodium copper chlorophyll (SCC). The capacity to inhibit the CL of three carbamates is in the order of carbaryl (CBL) >carbofuran (CBF) >metolcarb (MTC). Mechanisms of carbamates inhibiting SCC-luminol-H 2 O 2 CL are investigated using fluorescence quenching and quantum chemistry simulations for the first time in this work. Carbamate-SCC interactions studied using fluorescence spectroscopy show that with the increasing concentration of the SCC, the fluorescence of carbamate is quenched regularly, and the quenching mechanism is a static quenching process. Binding constants (KB) of the three carbamates with SCC are CBL (4.39 × 10 5) >CBF (1.46 × 10 4) >MTC (2.16 × 10 3 L/mol), which is completely harmonious with the capacity to inhibit CL of the carbamates. Furthermore, the carbamate-SCC interaction energies from quantum chemistry simulations are CBL-porphyrin copper (PPCu) (-30.1), CBF-PPCu (-21.0), and MTC-PPCu (-19.9 kJ/mol), which is also identical to their inhibiting capacity. This provides further evidence that the formation of carbamate-SCC complexes reduces the SCC catalytic activity and the CL intensity decreases. In addition, a novel flow injection chemiluminescence method for the determination of carbamate was established based on carbamate inhibiting CL of the SCC-luminol-H 2 O 2 CL system under alkaline conditions. This work may contribute to the study of the mechanism of CL inhibition using fluorescence quenching and quantum chemistry calculation methods.
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