Intranasal esketamine versus esketamine-dexmedetomidine combination for premedication in pediatric patients undergoing strabismus surgery: a randomized controlled trial.

Background: Preoperative fear and anxiety are prevalent in children undergoing surgery. The combination of esketamine and dexmedetomidine has been proposed as a promising premedication for enhancing preoperative sedation and analgesia. This study compared the premedication efficacy of intranasal esketamine alone and esketamine-dexmedetomidine combination in pediatric patients undergoing strabismus surgery. Methods: One hundred and eighty preschool children aged 2-6 years scheduled for strabismus surgery were enrolled and randomly assigned to one of the three groups: intranasal premedication with esketamine 2 mg/kg (Group K), esketamine 1 mg/kg and dexmedetomidine 1 µg/kg (Group KD1), or esketamine 0.5 mg/kg and dexmedetomidine 2 µg/kg (Group KD2). The primary outcome was the level of sedation following the intervention, as measured by the modified Yale preoperative anxiety scale (mYPAS) and sedation scale (SS). Secondary outcomes included onset time of sedation, the successful rate of peripheral intravenous cannulation, parental separation anxiety scale (PSAS), mask acceptance scale (MAS), wake-up time, duration of stay in the post-anesthesia care unit (PACU), and premedication-related adverse effects. Results: After premedication, the mYPAS score gradually decreased in the three groups, with lower values in Group K than in Group KD1 and Group KD2 patients in 1, 5, and 10 min. SS in Group KD1 and Group KD2 steadily increased until 40 min after premedication, while SS in Group K increased in the first 5 min after premedication and maintained consistent levels during the remaining time. Sedation onset was substantially faster in Group K patients (11.4±7.8 min) than Group KD1 (18.1±7.5 min, P=0.006) and Group KD2 (18.4±6.8 min, P<0.001). PSAS, separation status, the successful rate of peripheral intravenous cannulation, and MAS were comparable among groups. There was no significant difference in terms of emergence time or duration of stay in the PACU among groups. More gastrointestinal events were observed in Group K (P<0.001). Conclusions: Intranasal premedication with 2 mg/kg esketamine produced a more rapid onset of sedation accompanied by more gastrointestinal reactions compared with a combination of esketamine and dexmedetomidine. Trial Registration: ClinicalTrials.gov identifier: NCT04757675.

Efficacy of premedication with intravenous midazolam on preoperative anxiety and mask compliance in pediatric patients: a randomized controlled trial.

Background: To alleviate anxiety before surgery is a significant concern for the pediatric anesthesiologist. Midazolam has been generally used as a premedication, and compelling data regarding effective dose to mitigate anxiety is lacking. The current trial addressed the comparable efficacy of intravenous midazolam with different doses regarding the anxiety state, ease of child-parental separation, and mask compliance as premedication in pediatric patients undergoing tonsillectomy. Methods: Three hundred and twelve children aged 2-8 years were randomly assigned, 104 per group, to receive intravenous 0.03 mg/kg midazolam (group A), 0.05 mg/kg midazolam (group B), or saline control (group C), 40 minutes before surgery. We assessed the anxiety state every 10 min after premedication with modified Yale preoperative anxiety scale (mYPAS), evaluated the emotional state during separation with parental separation anxiety scale (PSAS), and compared their compliance to mask oxygen supply with mask acceptance score (MAS). Results: Children premedicated with 0.05 mg/kg midazolam achieved a sedated state more rapidly than those who received 0.03 mg/kg midazolam (5.9±2.3 vs. 7.0±3.9, P=0.02). The proportion of satisfactory parental separation and compliance to mask ventilation was not different between midazolam groups, which was superior to saline control. The children receiving 0.05 mg/kg midazolam stayed longer in postoperative care unit than those receiving 0.03 mg/kg midazolam and saline. The incidence of postoperative adverse events was rare and comparable among groups. Conclusions: Intravenous administration of a single dose of midazolam 0.05 and 0.03 mg/kg produces similar effects on sedation status, parental separation, and mask induction acceptance, except for rapid-onset and long sedation duration in pediatric patients premedicated with 0.05 mg/kg midazolam. Trial Registration: ClinicalTrials.gov NCT04266340.

RNA N1-methyladenosine regulator-mediated methylation modification patterns and heterogeneous signatures in glioma.

N1-methyladenosine (m1A) is ubiquitous in eukaryotic RNA and regulates mRNA translation. However, little is known about its regulatory role in glioma. Here, we identified 4 m1A modification-related patterns based on m1A regulators in the TCGA (The Cancer Genome Atlas) and CGGA (Chinese Glioma Genome Atlas) cohorts. The differences in survival prognosis between different clusters were striking. In addition, stemness, genomic heterogeneity, tumor microenvironment (TME), and immune cell infiltration were also significantly different between the poor and best prognostic clusters. To reveal the underlying mechanism, differentially expressed genes (DEGs) between the poor and best prognostic clusters were identified, and then were integrated for weighted correlation network analysis (WGCNA). After Univariate Cox-LASSO-Multivariate Cox analyses, DEGs PLEK2 and ABCC3 were screened as the risk-hub genes and were selected to construct an m1A-related signature. Moreover, ABCC3 exacerbated glioma proliferation and was associated with temozolomide (TMZ) resistance. Overall, our study provided new insights into the function and potential therapeutic role of m1A in glioma.

Alarm Signal S100-Related Signature Is Correlated with Tumor Microenvironment and Predicts Prognosis in Glioma.

Glioma are the most common malignant central nervous system tumor and are characterized by uncontrolled proliferation and resistance to therapy. Dysregulation of S100 proteins may augment tumor initiation, proliferation, and metastasis by modulating immune response. However, the comprehensive function and prognostic value of S100 proteins in glioma remain unclear. Here, we explored the expression profiles of 17 S100 family genes and constructed a high-efficient prediction model for glioma based on CGGA and TCGA datasets. Immune landscape analysis displayed that the distribution of immune scores, ESTIMATE scores, and stromal scores, as well as infiltrating immune cells (macrophages M0/M1/M2, T cell CD4+ naïve, Tregs, monocyte, neutrophil, and NK activated), were significant different between risk-score subgroups. Overall, we demonstrated the value of S100 protein-related signature in the prediction of glioma patients' prognosis and determined its relationship with the tumor microenvironment (TME) in glioma.

A Novel TAF-Related Signature Based on ECM Remodeling Genes Predicts Glioma Prognosis.

The composition and abundance of immune and stromal cells in the tumor microenvironment (TME) dramatically affect prognosis. Infiltration of immunosuppressive tumor-associated fibroblasts (TAFs) is a hallmark of glioma. However, the mechanisms regulating TAF infiltration and the prognostic value of TAF-related genes in glioma remain unclear. In this study, we analyzed TAF infiltration by Estimating the Proportion of Immune and Cancer cells (EPIC) algorithm based on multiple glioma databases, including Glioblastoma and low-grade glioma merged cohort from The Cancer Genome Atlas (TCGA GBMLGG) cohort, the Chinese Glioma Genome Atlas (CGGA) #325 cohort, and the CGGA #693 cohort. TAF infiltration was increased in glioblastoma (GBM), and elevated TAF infiltration predicted poorer survival in gliomas. Gene enrichment analyses revealed that differentially expressed genes (DEGs) between low-grade glioma (LGG) and GBM were significantly enriched in the extracellular matrix (ECM) remodeling-related signaling, which may contribute to immune escape and resistance to immune checkpoint blockers (ICBs). To identify co-expression modules and candidate hub genes that may be associated with TAF infiltration, we performed weighted correlation network analysis (WGCNA) of DEGs. Afterward, univariate Cox regression, least absolute shrinkage and selection operator (LASSO) regression, and multivariate Cox regression analyses were performed to screen the positive prognostic hub genes. Finally, a high-efficacy prediction signature was constructed based on the expression of S100A4, PLAUR, and EMP3. The signature correlated with the abundance of TAF infiltration in glioma and was an independent risk factor for glioma. In conclusion, our findings suggested that the TAF-related signature was a valuable prognostic biomarker in glioma and provided potential targets for integrative therapy of gliomas.

Mind-Body Exercises for Non-motor Symptoms of Patients With Parkinson's Disease: A Systematic Review and Meta-Analysis.

Objective: This study aimed to systematically evaluate the effects of mind-body exercise on global cognitive function, depression, sleep disorders, fatigue level, and quality of life (QOL) in a Parkinson's disease (PD) population. Methods: Total six English and Chinese databases were searched for articles published up to May 2021. Randomized controlled trials (RCTs) evaluating mind-body excises on non-motor symptoms of PD were included. The Cochrane risk of bias tool was used to assess the methodological quality, and we defined high-quality studies as having a low risk of bias in four or more domains. Global cognitive function was considered the primary outcome and was assessed using the Montreal Cognitive Assessment (MoCA). The secondary outcomes included QOL, fatigue, depression, and sleep quality, which were measured using the Parkinson's Disease Questionnaire (PDQ-39), 16-item Parkinson's Disease Fatigue Scale (PFS-16), Beck Depression Inventory (BDI), and revised Parkinson's Disease Sleep Scale (PDSS-2), respectively. Subgroup analyses were conducted for global cognitive function and QOL to assess the optimal treatment measure across the various mind-body exercises. Results: Fourteen RCTs with 404 patients were finally included in the meta-analysis. Eight (57.14%) studies were of high quality. The pooled results showed that mind-body exercises generally had a significant advantage over the control intervention in improving global cognitive function (MD = 1.68; P = 0.0008). The dose subgroup analysis revealed that the low dose (60-120 min per week) and moderate dose (120-200 min per week) significantly increased MoCA scores compared with the control group (MD = 2.11, P = 0.01; MD = 1.27, P = 0.02, respectively). The duration subgroup analysis indicated a significant difference in the effect of the duration (6-10 and >15 weeks) on increasing MoCA scores compared with the control group (MD = 3.74, P < 0.00001; MD = 1.45, P = 0.01, respectively). Conclusion: Mind-body exercise may improve global cognitive function, sleep quality, and QOL in the PD population. In addition, low to moderate doses and appropriate durations significantly improved global cognitive function. Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [CRD42021275522].

Gene Expression-Based Predication of RNA Pseudouridine Modification in Tumor Microenvironment and Prognosis of Glioma Patients.

Aberrant expression of methyltransferases and demethylases may augment tumor initiation, proliferation and metastasis through RNA modification, such as m6A and m5C. However, activity of pseudouridine (Ψ) modification of RNA remains unknown in glioma, the most common malignant intracranial tumor. In this study, we explored the expression profiles of the Ψ synthase genes in glioma and constructed an efficient prediction model for glioma prognosis based on the CGGA and TCGA datasets. In addition, the risk-score signature was positively associated with malignancy of gliomas and the abundance of tumor-infiltrating immune cells such as macrophages M0 and regulatory T cells (Tregs), but negatively associated with the abundance of monocytes, NK cell activation and T cell CD4+ naive. In terms of mechanism, the risk-score signature was positively associated with the expression of inflammatory molecules such as S100A11 and CASP4 in glioma. Overall, this study provided evidence for the activity of RNA Ψ modification in glioma malignancy and local immunity.

Effect of Escitalopram on Serum GDNF and BDNF Levels and 5-HT Level of Brain Tissue of Obsessive-Compulsive Disorder Rats.

The present study aims to discuss the effect of escitalopram in glial cell line-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF) levels, and 5-Hydroxytryptamine (5-HT) in obsessive-compulsive disorder rats. A total of 42 rats were divided into three groups randomly: control group (n = 14), model group (n = 14) (obsessive-compulsive disorder group), and escitalopram group (n = 14) (model + obsessive-compulsive disorder group + escitalopram treatment). The open-field method was used to test the rat behavior, enzyme-linked immunosorbent assay (ELISA) was used to determine the serum GDNF and BDNF levels. In addition, Western blot was used to determine the brain tissue protein levels of GDNF and BDNF and high-performance liquid chromatography + electrochemistry method to determine the 5-HT level of brain tissue. Visiting place was changed, rotational frequency and fixed duration enhanced in escitalopram group compared to model group (P < 0.05). Besides, GDNF and BDNF levels of serum and brain tissue were decreased in model group and escitalopram group compared to control group (P < 0.05), while GDNF and BDNF levels of serum and brain tissue were increased in escitalopram group compared to model group (P < 0.05). Moreover, the 5-HT level of brain tissue in escitalopram group was higher than that in model group (P < 0.05). Escitalopram could increase GDNF and BDNF levels and 5-HT content in serum and brain tissue in obsessive-compulsive disorder rats, which contributes to a function on the treatment of obsessive-compulsive disorder.

Enzymatic characterization and functional implication of two structurally different isocitrate dehydrogenases from Xylella fastidiosa.

Isocitrate dehydrogenase (IDH) is a key enzyme at the critical junction between the tricarboxylic acid cycle and the glyoxylate cycle. Most bacteria have only one IDH, while a few contain two IDH isozymes. The coexistence of two different type IDHs in one organism was little known. Xylella fastidiosa is a nutritionally fastidious plant pathogen that contains two structurally different IDHs, an NAD+ -dependent homodimeric IDH (diXfIDH) and an NADP+ -dependent monomeric IDH (monoXfIDH). Kinetic characterization showed that diXfIDH displayed 206-fold preferences for NAD+ over NADP+ , while monoXfIDH showed 13,800-fold preferences for NADP+ over NAD+ . The putative coenzyme crucial amino acids (Asp-268, Ile-269, and Ala-275 in diXfIDH, and Lys-589, His-590, and Arg-601 in monoXfIDH) were studied by site-directed mutagenesis. The coenzyme specificities of the three diXfIDH mutants (D268K, D268K/I269Y, and D268K/I269Y/A275V) were switched successfully from NAD+ to NADP+ . Meanwhile, the mutant monoXfIDHs (H590L/R601L and K589T/H590L/R601L) greatly reduced the affinity for NADP+ , but failed to improve the ability to use NAD+ and had similar affinity to NADP+ and NAD+ . The biochemical properties of diXfIDH and monoXfIDH were investigated in detail. This study gives a further insight into the determinants of the coenzyme specificity in both monomeric and dimeric forms of IDHs.