Drug Design, Development and Therapy最新文献

Purpose: This study aimed to establish the 95% effective dose (ED95) of esketamine in combination with propofol for hysteroscopy and then to evaluate its efficacy and safety profile.

Patients and methods: This prospective, double-blind, randomized controlled trial consisted of two cohorts. In cohort 1, 45 women aged 18-65 years undergoing hysteroscopy were randomly assigned to either group E (esketamine + propofol) or group A (alfentanil + propofol). Dixon's up-and-down method was used to determine the ED95 of esketamine and alfentanil. In cohort 2, 86 patients were randomized to group E and group A, with the calculated ED95 dose of the study drugs used for induction. The success rate of anesthesia using the ED95% dose, along with parameters related to anesthesia induction, recovery, and adverse events were also recorded.

Results: The ED95 of esketamine was 0.254 mg/kg (95% CI: 0.214-1.004), while that of alfentanil was 9.121 μg/kg (95% CI: 8.479-13.364). The anesthesia success rate was 93.0% in group E and 95.2% in group A (p = 0.664). After resuscitation, both groups achieved a 100% success rate. The induction time was significantly shorter in group E (60.0 [55.0-70.0] s) compared to group A (67.0 [61.0-79.3] s) (p = 0.006). Group E had lower rates of respiratory depression (p < 0.001), hypoxia (p = 0.006), minimum perioperative SpO₂ (p = 0.010), and hypotension (p = 0.001). Esketamine had less effect on respiratory rate, heart rate, mean blood pressure, and end-tidal carbon dioxide compared to alfentanil (all p < 0.001). There were no significant differences in postoperative pain between the two groups.

Conclusion: This study determined the ED 95 dose of esketamine for intravenous general anesthesia during hysteroscopy. Esketamine showed less respiratory and hemodynamic depression, as well as fewer adverse effects compared to alfentanil. Esketamine is an ideal anesthetic agent compared to alfentanil for hysteroscopic anesthesia.

Trial registration: www.chictr.org.cn, (ChiCTR2300077283); registered November 3, 2023.

Objective: Hepatotoxicity is an important cause of early withdrawal of voriconazole (VCZ). The role of the plasma trough concentration of VCZ (C₀) in hepatotoxicity is confusion. VCZ N-oxide is the primary metabolite of VCZ in plasma. We investigated the role of VCZ C₀ and plasma trough concentration of VCZ N-oxide (C_N) in hepatotoxicity in adult patients.

Materials and methods: This was a prospective study. VCZ C₀ and C_N were measured using liquid chromatography-tandem mass spectrometry.

Results: In total, 601 VCZ C₀ and C_N from 376 adult patients were included. The percentage of grade 1 or higher adverse events for ALP, ALT, AST, γ-GT, and TBIL were 35.4%, 21.0%, 30.1%, 56.2%, and 22.2%, respectively. Compared with younger adult patients, elderly patients (≥65 years) had a higher rate of grade 1 or higher adverse events of ALP. In the multivariate analysis, VCZ C₀ was a risk factor for grade 1 or higher adverse events of AST in elderly patients and TBIL in younger adult patients, and VCZ C_N was a risk factor for grade 1 or higher adverse events of ALT, AST, and TBIL. Results of the receiver operating characteristic curve analysis indicated that when the VCZ C₀ was higher than 4.0 μg/mL, or the VCZ C_N was lower than 1.7 μg/mL, the incidence of grade 1 or higher adverse events of AST and TBIL increased.

Conclusion: VCZ C₀ and C_N were associated with liver function-related adverse events. Measurement of VCZ C_N should be considered for VCZ therapeutic drug monitoring.

Background: Diabetes mellitus is a complex metabolic disorder that has an enormous impact on people's quality of life and health. Although there is no doubt about the effectiveness of oral hypoglycemic agents combined with lifestyle management in controlling diabetes, no individual has ever been reported to have been completely cured of the disease. Globally, many medicinal plants have been used for the management of diabetes in various traditional systems of medicine. A deep look in the literature has revealed that the Liliaceae family have been poorly investigated for their antidiabetic activity and phytochemical studies. In this review, we summarize medicinal plants of Liliaceae utilized in the management of type II diabetes mellitus (T2DM) by inhibition of α-glucosidase enzyme and phytochemical content.

Methods: The literature search was conducted using databases including PubMed, ScienceDirect, and Google Scholar to find the significant published articles about Liliaceae plants utilized in the prevention and treatment of antidiabetics. Data were filtered to the publication period from 2013 to 2023, free full text and only English articles were included. The keywords were Liliaceae OR Alliaceae OR Amaryllidaceae AND Antidiabetic OR α-glucosidase.

Results: Six medicinal plants such as Allium ascalonicum, Allium cepa, Allium sativum, Aloe ferox, Anemarrhena asphodeloides, and Eremurus himalaicus are summarized. Phytochemical and α-glucosidase enzymes inhibition by in vitro, in vivo, and human studies are reported.

Conclusion: Plants of Liliaceae are potential as medicine herbs to regulating PPHG and prevent the progression of T2DM and its complication. In silico study, clinical application, and toxicity evaluation are needed to be investigated in the future.

Objective: Nanomedicine represents a transformative approach in biomedical applications. This study aims to delineate the application of nanomedicine in the biomedical field through the strengths, weaknesses, opportunities, and threats (SWOT) analysis to evaluate its efficacy and potential in clinical applications.

Methods: The SWOT analysis framework was employed to systematically review and assess the internal strengths and weaknesses, along with external opportunities and threats of nanomedicine. This method provides a balanced consideration of the potential benefits and challenges.

Results: Findings from the SWOT analysis indicate that nanomedicine presents significant potential in drug delivery, diagnostic imaging, and tissue engineering. Nonetheless, it faces substantial hurdles such as safety issues, environmental concerns, and high development costs. Critical areas for development were identified, particularly concerning its therapeutic potential and the uncertainties surrounding long-term effects.

Conclusion: Nanomedicine holds substantial promise in driving medical innovation. However, successful clinical translation requires addressing safety, cost, and regulatory challenges. Interdisciplinary collaboration and comprehensive strategic planning are crucial for the safe and effective application of nanomedicine.

Purpose: Anxiety and depression can affect the physiology of the gastrointestinal tract through the brain-gut axis, causing gastrointestinal dysfunction, which is mainly manifested as indigestion, diarrhoea, constipation, or abdominal pain. Preoperative anxiety arises in children due to separation from parents, fear of unfamiliar surroundings and anaesthesia and surgical procedures.To discuss the effect of alleviating preoperative anxiety on postoperative recovery of gastrointestinal function in children with indirect inguinal hernia after laparoscopic high ligation of the hernia sac.

Patients and methods: 90 children with laparoscopic high ligation of the herniated sac in oblique inguinal hernia were randomly divided into control group (Group C) and experimental group (Group M). The Group M was given midazolam oral solution 0.5mg/kg (maximum dose 20mg), and The Group C was given 5% glucose solution with the same dose.Primary outcome was the time to first postoperative defecation and I-FEED scores.The secondary outcomes included mYPAS-SF scores; child sedation scores; child-parent separation scores; parental STAI scores;PHBQ scores;FLACC scores, operative time, and fluid input and surgeon job satisfaction.

Results: Compared with Group C, there was a shorter time to first postoperative defecation (P < 0.05), and lower I-FEED scores on postoperative day 1 (P < 0.05). The mYPAS-SF scores, which were significantly different in Group M at T1, T2, and T3 (P < 0.05), parental STAI scores at S1, child sedation scores and child-parent separation scores in T1, and surgeon job satisfaction between the two groups were significantly different (P < 0.05). There were no statistically significant differences in I-FEED scores on days 2 and 3, PHBQ scores, FLACC scores, operative time, and fluid input between the two groups of children (P > 0.05).

Conclusion: Preoperative application of midazolam oral solution to relieve preoperative anxiety helps to promote the recovery of postoperative gastrointestinal function in children with indirect inguinal hernia and increases the surgeon job satisfaction.

Remimazolam is a novel ultra-short-acting benzodiazepine with a unique pharmacokinetic profile that makes it an attractive option for use in general anesthesia. This review paper provides an in-depth analysis of remimazolam's applications in the field of general anesthesia, focusing on its pharmacological properties, clinical efficacy, safety profile, and potential advantages compared to other anesthetic agents. Remimazolam acts on GABAa receptors, offering rapid onset and recovery times due to its unique metabolic pathway involving tissue esterases. Clinical trials have demonstrated its efficacy in procedural sedation and general anesthesia, showing a favorable safety profile with minimal cardiovascular and respiratory depression. Compared to traditional anesthetics such as propofol, remimazolam presents distinct advantages, including predictable pharmacokinetics, reduced risk of prolonged sedation, and a reliable safety margin. These attributes position remimazolam as a promising agent in various clinical settings. The purpose of this review is to synthesize current evidence on remimazolam and discuss its potential to improve clinical outcomes in anesthesia practice.