The Median Effective Dose and Bispectral Index of Remimazolam Tosilate for Anesthesia Induction in Elderly Patients: An Up-and-Down Sequential Allocation Trial.

Purpose: Remimazolam is a new type of ultrashort benzodiazepine drug with an unclear optimal dose for general anesthesia induction in elderly patients aged >60 years. Therefore, this study aimed to determine the effective dose of remimazolam tosilate induction and explore its correlation with the bispectral index (BIS). Patients and Methods: A total of 42 elderly patients were divided into two age groups: 60-69 (group A) and 70-85 (group B) years. An initial dose of 0.1mg/kg(Group A) and 0.05 mg/kg(Group B) remimazolam tosilate was administered, and the Modified Observer's Assessment of Alertness/Sedation scale was used to assess adequate responses. The dose was calculated using the up-and-down allocation technique based on the previous response. The sequential formula and probit regression model were used to calculate ED50 and BIS50. ED95 was determined using the probit regression model. Results: The ED50 of remimazolam tosilate for anesthesia induction were 0.088 mg/kg (95% confidence interval [CI] 0.071-0.108) and 0.061 mg/kg (95% CI 0.053-0.069) in groups A and B, respectively. ED95 was 0.118 mg/kg (95% CI 0.103-0.649) and 0.090 mg/kg (95% CI 0.075-0.199) in groups A and B, respectively. The remimazolam tosilate administration could decrease BIS. BIS50 was 86.0 (95% CI 83.7-88.6) and 85.4 (95% CI 84.1-86.8) in groups A and B, respectively. Conclusion: During the induction process, patients' consciousness should be observed. The dose of remimazolam tosilate could be chosen after careful consideration of individual variations.

Transmembrane Protein 166 and its Significance.

Transmembrane protein 166 (TMEM166) is a lysosomal/endoplasmic reticulum (ER)-associated protein found in different species where it functions as a regulator of programmed cell death through autophagy and apoptosis. It is expressed in a variety of normal tissues and organs, and it is involved in a wide variety of physiological and pathological processes, including cancers, infection, autoimmune diseases, and neurodegenerative diseases. Previous studies indicated that TMEM166 is associated with autophagosomal membrane development. TMEM166 can cause lysosomal membrane permeabilization (LMP) leading to the release of proteolytic enzymes, e.g., cathepsins, that may cause potential mitochondrial membrane damage, which triggers several autophagic and apoptotic events. A low level of TMEM166 expression is also found in tumors, while high level of TMEM166 is found in brain ischemia. In addition, loss of TMEM166 leads to impaired NSC self-renewal and differentiation along with a decrease in autophagy. These findings offer a comprehensive understanding of the pathways involved in the role of TMEM166 in programmed cell death and treatment of various diseases.

Oxycodone suppresses the lipopolysaccharide-induced neuroinflammation by downregulating nuclear factor-κB in hippocampal astrocytes of Sprague-Dawley rats.

Neuroinflammation is a common pathogenic mechanism in several neurodegenerative diseases, and glial cells are the primary inflammatory mediators of the central nervous system (CNS). Acute neuronal injury, infection, and chronic neurodegeneration may induce astrocyte activation, which is a response characterized by hyperproliferation and release of multiple inflammatory signaling factors. The opioid analgesic oxycodone has demonstrated anti-inflammatory efficacy in peripheral tissue, but its effects on the CNS have not been studied. We evaluated the inhibitory effects of oxycodone on astrocyte activation and proinflammatory mediator production in response to lipopolysaccharide (LPS). Our results showed that oxycodone (5-20 µg/ml) dose-dependently inhibited the LPS-induced astrocytosis, as measured by 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide and bromodeoxyuridine assays, as well as the overexpression of glial fibrillary acidic protein, which are two hallmarks of reactive astrogliosis in neurodegenerative diseases. Oxycodone also decreased both the mRNA and protein expression levels of proinflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1ß. Besides, oxycodone increased the expression of the nuclear factor kappa-B (NF-κB) endogenous inhibitor IκB-α, and blocked NF-κB translocation to the nucleus. The anti-inflammatory efficacy of oxycodone on rat astrocytes increased with pretreatment duration. These results suggest that oxycodone can suppress neuroinflammation by inhibiting NF-κB signaling in astrocytes. Targeting the astrocytic NF-κB-mediated inflammatory response may be an effective therapeutic strategy against diseases involving neuroinflammatory damage.

Clinical features and disease progression in moyamoya disease patients with Graves disease.

OBJECT: The present study aimed to clarify the incidence and clinical features of disease progression in adult moyamoya disease (MMD) patients with Graves disease (GD) for better management of these patients. METHODS: During the past 18 years, 320 adult Chinese patients at West China Hospital were diagnosed with MMD, and 29 were also diagnosed with GD. A total of 170 patients (25 with GD; 145 without GD) were included in this study and were followed up. The mean follow-up was 106.4 ± 48.6 months (range 6-216 months). The progression of the occlusive lesions in the major intracranial arteries was measured using cerebral angiography and was evaluated according to Suzuki's angiographic staging. Information about cerebrovascular strokes was obtained from the records of patients' recent clinical visits. Both angiographic progression and strokes were analyzed to estimate the incidences of angiographic progression and strokes using Kaplan-Meier analysis. A multivariate logistic regression model was used to test the effects of sex, age at MMD onset, disease type, strokes, and GD on the onset of MMD progression during follow-up. RESULTS: During follow-up, the incidence of disease progression in MMD patients with GD was significantly higher than in patients without GD (40.0% vs 20.7%, respectively; p = 0.036). The interval between initial diagnosis and disease progression was significantly shorter in MMD patients with GD than in patients without GD (p = 0.041). Disease progression occurred in both unilateral MMD and bilateral MMD, but the interval before disease progression in patients with unilateral disease was significantly longer than in patients with bilateral disease (p = 0.021). The incidence of strokes in MMD patients with GD was significantly higher than in patients without GD (48% vs 26.2%, respectively; p = 0.027). The Kaplan-Meier survival curve showed significant differences in the incidence of disease progression (p = 0.038, log-rank test) and strokes (p = 0.031, log-rank test) between MMD patients with GD and those without GD. Multivariate analysis suggested that GD may contribute to disease progression in MMD (OR 5.97, 95% CI 1.24-33.76, p = 0.043). CONCLUSIONS: The incidence of disease progression in MMD patients with GD was significantly higher than that in MMD patients without GD, and GD may contribute to disease progression in MMD patients. The incidence of strokes was significantly higher in MMD patients with GD than in patients without GD. Management guidelines for MMD patients with GD should be developed.