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Objective: To investigate the effect of parental presence during induction of anesthesia (PPIA) in relieving preoperative anxiety of children undergoing tonsillectomy and adenoidectomy., Methods: One hundred and sixty children undergoing tonsillectomy and adenoidectomy were divided into the control group and the trial group. The control group received routine nursing in the operation room, while anesthesia was induced in the trial group children in the presence of their parents as part of the routine nursing. The differences in heart rate and mean dynamic pressure during pre-operative visit and anesthesia induction between the two groups were observed and recorded. The Modified Yale Preoperative Anxiety Scale (m-YPAS) and the Induction Compliance Checklist (ICC) were scored. The anxiety status of the children and their family members in the two groups was scored at different times, and the psychological stress of anesthesiologists during anesthesia induction was scored by a visual analogue scale. The differences in each index between the two groups were compared. Operation time and costs in-hospital were also compared., Results: Compared with the control group, the heart rate and blood pressure scores as well as the ICC in the trial group were lower than those in the control group (P < 0.01). On comparing the scores of m-YPAS between the two groups, we observed that the scores of the children in the trial group were lower than those in the control group before entering the induction room and anesthesia induction (P < 0.01). There was no statistical difference between the scores of the children in the trial group and the control group on the day of operation and on the way to the operating room (P > 0.05). The nursing satisfaction scores of the family members in the trial group were significantly superior to those in the control group (P < 0.01). The scores of the visual analogue scale for psychological pressure of anesthesiologists during anesthesia induction were higher in the trial group than in the control group (P < 0.05). The operation time and costs in study group were both significantly higher than those of control group (P < 0.05)., Conclusion: PPIA can significantly reduce preoperative anxiety and surgical physiological stress response in children undergoing tonsillectomy and adenoidectomy, and it is worth being encouraged., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Neuroblastoma is the most common and deadliest tumor in infancy. WDR5 (WD Repeat Domain 5), a critical factor supporting an N-myc transcriptional complex via its WBM site and interacting with chromosome via its WIN site, promotes the progression of neuroblastoma, thus making it a potential anti-neuroblastoma drug target. So far, a few WIN site inhibitors have been reported, and the WBM site disruptors are rare to see. In this study we conducted virtual screening to identify candidate hit compounds targeting the WBM site of WDR5. As a result, 60 compounds were selected as candidate WBM site inhibitors. Cell proliferation assay demonstrated 6 structurally distinct WBM site inhibitors, numbering as compounds 4, 7, 11, 13, 19 and 22, which potently suppressed 3 neuroblastoma cell lines (MYCN-amplified IMR32 and LAN5 cell lines, and MYCN-unamplified SK-N-AS cell line). Among them, compound 19 suppressed the proliferation of IMR32 and LAN5 cells with EC 50 values of 12.34 and 14.89 μM, respectively, and exerted a moderate inhibition on SK-N-AS cells, without affecting HEK293T cells at 20 μM. Analysis of high-resolution crystal complex structure of compound 19 against WDR5 revealed that it competitively occupied the hydrophobic pocket where V264 was located, which might disrupt the interaction of MYC with WDR5 and further MYC-medicated gene transcription. By performing RNA-seq analysis we demonstrated the differences in molecular action mechanisms of the compound 19 and a WIN site inhibitor OICR-9429. Most interestingly, we established the particularly high synergy rate by combining WBM site inhibitor 19 and the WIN site inhibitor OICR-9429, providing a novel therapeutic avenue for neuroblastoma., (© 2022. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Understanding the future distribution of antibiotic resistance in natural soil ecosystems is important to forecast their impacts on ecosystem and human health under projected climate change scenarios. Therefore, it is critical and timely to decipher the links between climate warming and antibiotic resistance, two of Earth's most imminent problems. Here, we explored the role of five-year simulated climate warming (+ 4 °C) on the diversity and proportions of soil antibiotic resistance genes (ARGs) across three seasons in both plantation and natural forest ecosystems. We found that the positive effects of warming on the number and proportions of ARGs were dependent on the sampling seasons (summer, autumn and winter), and seasonality was a key factor driving the patterns of ARG compositions in forest soils. Fifteen ARGs, conferring resistance to common antibiotics including aminoglycoside, beta-lactam, macrolide-lincosamide-streptogramin B, multidrug, sulfonamide, and tetracycline, were significantly enriched in the warming treatment. We showed that changes in soil properties and community compositions of bacteria, fungi and protists can explain the changes in soil ARGs under climate warming. Taken together, these findings advance our understanding of environmental ARGs under the context of future climate change and suggest that elevated temperature may promote the abundance of specific soil ARGs, with important implications for ecosystem and human health., (Copyright © 2022 Elsevier B.V. All rights reserved.)

An epidemic of pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading worldwide. SARS-CoV-2 relies on its spike protein to invade host cells by interacting with the human receptor protein Angiotensin-Converting Enzymes 2 (ACE2). Therefore, designing an antibody or small-molecular entry blockers is of great significance for virus prevention and treatment. This study identified five potential small molecular anti-virus blockers via targeting SARS-CoV-2 spike protein by combining in silico technologies with in vitro experimental methods. The five molecules were natural products that binding to the RBD domain of SARS-CoV-2 was qualitatively and quantitively validated by both native Mass Spectrometry (MS) and Surface Plasmon Resonance (SPR). Anti-viral activity assays showed that the optimal molecule, H69C2, had a strong binding affinity (dissociation constant K D ) of 0.0947 µM and anti-virus IC 50 of 85.75 µM., (© 2021. The Author(s), under exclusive licence to CPS and SIMM.)

The COVID-19, caused by SARS-CoV-2, is threatening public health, and there is no effective treatment. In this study, we have implemented a multi-targeted anti-viral drug design strategy to discover highly potent SARS-CoV-2 inhibitors, which simultaneously act on the host ribosome, viral RNA as well as RNA-dependent RNA polymerases, and nucleocapsid protein of the virus, to impair viral translation, frameshifting, replication, and assembly. Driven by this strategy, three alkaloids, including lycorine, emetine, and cephaeline, were discovered to inhibit SARS-CoV-2 with EC 50 values of low nanomolar levels potently. The findings in this work demonstrate the feasibility of this multi-targeting drug design strategy and provide a rationale for designing more potent anti-virus drugs., (© 2021. The Author(s), under exclusive licence to CPS and SIMM.)

A versatile method for the rapid synthesis of diverse functionalized pyrazolines has been developed based on copper-mediated aminofunctionalization of β,γ-unsaturated hydrazones. The scope of this strategy encompasses a range of difunctionalization reactions: aminoazidation, aminohalogenation, and aminothiocyanation. These reactions provide straightforward access to a series of useful pyrazoline building blocks containing various functional groups that are hard to access traditionally.

An efficient and step-economical copper-mediated intra-/intermolecular aminoacyloxylation of β,γ-unsaturated hydrazones has been developed. Copper carboxylates serve as both reaction promoters and carboxylate sources in these easily conducted reactions. This method provides straightforward access to diversely useful acyloxyl pyrazolines, which are hard to access traditionally, in good to excellent yields.

A convenient copper-catalyzed intra-/intermolecular diamination of β,γ-unsaturated hydrazones has been developed with simple amines as external amine sources. The protocol enables efficient access to various nitrogen-containing pyrazolines under mild reaction conditions.

Background: The high incidence of cognition disorders in chronic obstructive pulmonary disease (COPD) patients represents a main focus in public health field recently. Thus, we tried to explore relationship between cognitive function and arterial partial pressure O2 (PaO2) in patients with COPD as assessed by Mini-mental State Examination (MMSE) and/or Montreal Cognitive Assessment (MoCA)., Materials and Methods: Medical and scientific literature databases, such as Web of Science, PubMed, Cochrane Library, China National Knowledge Infrastructure, and Wanfang Database, were searched independently by 2 reviewers until February 2016. Correlation coefficient (r or rs) values were obtained from each study, and 95% confidence intervals (CIs) were calculated using STATA12.0 software., Results: A total of 2049 studies were produced, and 9 of which were analyzed (714 participants) in the meta-analysis. The pooled r observed medium relationship for all selected studies (r = 0.405, 95% CI 0.31-0.55), and notable heterogeneity was also tested between studies (χ = 17.72, P = .023; I = 54.9%). After the sensitivity and subgroup analysis, the heterogeneity significantly decreased. Subgroup analysis showed that MMSE score was stronger correlation between PaO2 and cognitive function than MoCA score in the COPD patients. Begg test did not indicate potential risk of publication bias., Conclusions: There was a negative correlation between cognitive function and anoxia in patients with COPD, so it may be extremely essential to predict and improve the status of hypoxia in COPD patients.

The seven-helical bundle of rhodopsin and other G-protein coupled receptors undergoes structural rearrangements as the transmembrane receptor protein is activated. These structural changes are known to involve tilting and bending of various transmembrane helices. However, the cause and effect relationship among structural events leading to a cytoplasmic crevasse for G-protein binding is less well defined. Here we present a mathematical model of the protein helix and a simple procedure to determine multiple parameters that offer precise depiction of a helical conformation. A comprehensive survey of bovine rhodopsin structures shows that the helical rearrangements during the activation of rhodopsin involve a variety of angular and linear motions such as torsion, unwinding, and sliding in addition to the previously reported tilting and bending. These hitherto undefined motion components unify the results obtained from different experimental approaches, and demonstrate conformational similarity between the active opsin structure and the photoactivated structures in crystallo near the retinal anchor despite their marked differences.

In vitro lymphocyte stimulation reaction to retinal S-antigen was evaluated in 115 patients of anterior uveitis, posterior uveitis/pan-uveitis, and optic neuritis, the positive rate being 34% (18/53), 41.5% (17/41), and 57.1% (12/21) respectively. It is speculated that such immunoresponse may be secondary to the exposition or the release of retinal antigens by various causes, leading to activation or augmentation of meager or low-affinity S-antigen-specific lymphocytes in healthy individuals to start the pathogenic autoimmune process. However, the authors also found that the stimulation index to PHA differed insignificantly between the control and experimental groups, indicating that there was no cellular immuno-hypofunction in the experimental patients.

Experimental autoimmune uveitis (EAU) was induced in 95% of guinea pigs after immunization by a single intradermal injection of homologous retinal tissue in Freund's complete adjuvant and subcutaneous injection of dead pertussis bacilli. The clinical features were circumcorneal injection, cells and flare in the anterior chamber, vasodilation in the iris, and marked cellular exudate in the vitreous. The pathological changes were characterized by diffuse proliferative granulomatous panuveitis, consisting of lymphocytes, macrophages, and epithelioid cells. The outer layers of the retina were disrupted or missing in areas where the pigment epithelium was damaged.