Objective To observe the relationship between 5-Hydroxytryptamine(5-HT)-like immunoreactive terminals and the vestibulo-parabrachial nucleus projection neurons which may express 5-HT1A receptor in the vestibular nuclear complex(VNC). Methods Retrograded-tract tracing technique combined with double labeling of immunofluorescence histochemical was used,and the stained sections were observed under a confocal laser-scanning microscope. Results Following injection of tetramethylrhodamine(TMR) into the parabrachial nucleus, many retrogradely labeled neurons were observed bilaterally within VNC,but with an ipsilateral predominance.Immunofluorescence histochemical staining showed that many neurons expressed(5-HT1A) receptor-like immunoreactivity and a large number of 5-HT immunostained fibers or terminals were found in the medial,spinal,superior,lateral vestibular nucleus(MVe,SpVe,SuVe,LVe),X nucleus and Y nucleus.Confocal laser-scanning microscopy revealed that some TMR-labeled neurons were 5-HT_1AR immunopositive,and some of the cell bodies or dendrites of TMR/5-HT1AR double-labeled neurons were closely apposed by 5-HT-like immunoreactive terminals.Conclusion The present study suggests that 5-HT may modulate vestibular signals along the VNC-parabrachial nucleus pathway via 5-HT1A receptor.

In this study, pregabalin controlled porosity osmotic pump tablets which are taken once a day were prepared. Single-factor tests were carried out to investigate the influence of excipients and manufacturing process. The formulation was optimized through orthogonal experiment on three levels of three significant factors including the amount of sodium citrate, and polyethylene glycol 400 and coating weight gain. On the basis of the results of the single-factor tests and the orthogonal experiment, optimal formulation and manufacturing process were obtained. The final tablet formulation contained pregabalin(82. 5 mg), microcrystalline cellulose(40%), sodium citrate(27. 5%), magnesium stearate(0. 5%)and 5% povidone K30 solution as the tablet binder; the coating formulation consisted of cellulose acetrate and 60% of polyethylene glycol 400 as a porogen; the coating weight gain was 3%. In vitro drug release kinetic study suggested that the drug release from controlled porosity osmotic pump tablets was mainly driven by osmotic pressure, which was barely affected by the pH of the release medium. The drug release behavior of the tablets within 12 hours complied with zero-order release rule and the linear correlation coefficient was 0. 991 6. The obtained porosity osmotic pump tablets could effectively slow the drug release rate, reduce concentration fluctuation and improve the safety and convenience for the patients, hence with broad prospects.

Objective:To investigate the current sedation level of patients with mechanical ventilation in ICU, and to explore the influence of early different sedation levels on clinical outcomes, so as to provide theoretical basis for better guidance of clinical sedation evaluation and implementation of sedation strategy management.Methods:This study was a retrospective longitudinal study. The 201 patients with invasive mechanical ventilation who underwent sedation in the Department of Intensive Care Medicine of the First Affiliated Hospital of Guangxi Medical University from January to December 2021 were selected by convenience sampling method. According to the results of Richmond Agitation-Sedation Scale(RASS), the patients were divided into deep sedation group (98 cases) and shallow sedation group (103 cases). The influencing factors of endotracheal intubation retention time and outcome were investigated by Cox multifactor analysis.Results:In the early sedation ≤48 h after the start of mechanical ventilation, 63.2%(2 143/3 389) of patients with invasive mechanical ventilation had a RASS score of shallow sedation, 35.2%(1 194/3 389) of patients with deep sedation, and 1.5%(52/3 389) of patients with insufficient sedation. Cox multivariate regression analysis showed that age, sedation level, duration of invasive mechanical ventilation and continuous renal replacement therapy were the factors influencing the indentation time of tracheal insertion ( χ2 values were 4.73 to 74.31, all P<0.05); early deep sedation was a risk factor for delayed extubation ( HR=0.499, 95% CI 0.276-0.903, P<0.05); gender, sedation level, invasive mechanical ventilation duration, acute physiology and chronic health evaluation Ⅱ scores, admission mode, continuous renal replacement therapywere the influencing factors of patient outcomes ( χ2 values were 4.41 to 26.20, all P<0.05). The deeper the sedation, the worse the patient outcomes ( HR=0.568, 95% CI 0.335-0.963 all P<0.05) . Conclusions:The early sedation level is related to the retention time and outcome of tracheal intubation in ICU patients with mechanical ventilation, and different sedation levels affect the clinical outcome of patients. The retention time of tracheal intubation in patients with shallow sedation was shortened, which was beneficial to the outcome of patients.Therefore, sedation evaluation should be strengthened in clinical work, and sedation methods should be selected according to the needs of patients. In the absence of contraindications, the shallow sedation strategy should be implemented as soon as possible. This study provides some reference and theoretical basis for the formulation and management of clinical sedation strategies.