Effects of remimazolam combined with sufentanil on hemodynamics during anesthetic induction in elderly patients with mild hypertension undergoing orthopedic surgery of the lower limbs: a randomized controlled trial.

BACKGROUND: This randomized controlled trial was performed to observe the effect of remimazolam with sufentanil on hemodynamics during anesthetic induction in elderly patients with mild hypertension undergoing orthopedic surgery of the lower limbs. METHODS: Sixty elderly patients were randomly assigned to undergo general anesthesia with intravenous injection of either remimazolam besylate (25 mg/vial, batch number 10T11011; Yichang Humanwell Pharmaceutical Co., Ltd., Yichang, China) at 0.2 mg/kg (Group R, n = 30) or propofol at 1.5 mg/kg (Group P, n = 30). Both injections were completed within 15 to 20 s. If the bispectral index value did not reach 40 to 60, then 0.05 mg/kg of remimazolam was added in Group P and 1 mg/kg of propofol was added in Group R. When the BIS value reached 40 to 60, sufentanil was administered at 0.3 to 0.5 µg/kg and cisatracurium was administered at 0.15 to 0.2 mg/kg in both groups. Three minutes later, tracheal intubation and controlled ventilation were performed to maintain the end-tidal carbon dioxide partial pressure at 4.5 to 5.0 kPa. The mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), continuous cardiac index (CI), systemic vascular resistance (SVR), and pulse oxygen saturation were recorded before induction (T0), when the eyelash reflex disappeared (T1), immediately after endotracheal intubation (T2), 1 min after endotracheal intubation (T3), and 5 min after endotracheal intubation (T4). The disappearance time of the eyelash reflex, injection pain, hypotension, bradycardia, hiccupping, nausea and vomiting, and other adverse events were observed. RESULTS: The MAP, HR, CO, and CI at T1, T2, T3, and T4 were significantly higher in Group R than P, while SVR was significantly lower in Group R than P (P < 0.05). In Group P, the MAP, HR, CO, and CI were significantly lower and the SVR was significantly higher at T1, T2, T3, and T4 than at T0 (P < 0.05). Adverse events occurred in 8 (20%) patients in Group R and 22 (73%) in Group P. The total incidence of adverse events was significantly lower in Group R than P (P < 0 0.001). CONCLUSION: Remimazolam combined with sufentanil for general anesthesia induction has the advantages of small hemodynamic fluctuations, stable circulation, and few adverse reactions, making it suitable for elderly patients with mild hypertension. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2300069224, 10/03/2023).

Upregulation of miR-499a-5p Decreases Cerebral Ischemia/Reperfusion Injury by Targeting PDCD4.

MiR-499a-5p was significantly downregulated in degenerative tissues and correlated with apoptosis. Nonetheless, the biological function of miR-499a-5p in acute ischemic stroke has been still unclear. In this study, we found that the plasma levels of miR-499a-5p were significantly downregulated in 64 ischemic stroke patients and negatively correlated with the National Institutes of Health Stroke Scale score. Then, we constructed cerebral ischemia/reperfusion (I/R) injury in rats after middle cerebral artery occlusion and subsequent reperfusion and oxygen-glucose deprivation and reoxygenation (OGD/R)-treated SH-SY5Y cell model. Transfection with miR-499a-5p mimic was accomplished by intracerebroventricular injection in the in vivo I/R injury model. We further found that miR-499a-5p overexpression decreased infarct volumes and cell apoptosis in the in vivo I/R stroke model using TTC and TUNEL staining. PDCD4 was a direct target of miR-499a-5p by luciferase report assay and Western blotting. Knockdown of PDCD4 reduced the infarct damage and cortical neuron apoptosis caused by I/R injury. MiR-499a-5p exerted neuroprotective roles mainly through inhibiting PDCD4-mediated apoptosis by CCK-8 assay, LDH release assay, and flow cytometry analysis. These findings suggest that miR-499a-5p might represent a novel target that regulates brain injury by inhibiting PDCD4-mediating apoptosis.

Long noncoding RNA TUG1 contributes to cerebral ischaemia/reperfusion injury by sponging mir-145 to up-regulate AQP4 expression.

Emerging studies have shown that long noncoding RNA (lncRNA) TUG1 (taurine-up-regulated gene 1) plays critical roles in multiple biological processes. However, the expression and function of lncRNA TUG1 in cerebral ischaemia/reperfusion injury have not been reported yet. In this study, we found that LncRNA TUG1 expression was significantly up-regulated in cultured MA-C cells exposed to OGD/R injury, while similar results were also observed in MCAO model. Mechanistically, knockdown of TUG1 decreased lactate dehydrogenase levels and the ratio of apoptotic cells and promoted cell survival in vitro. Moreover, knockdown of TUG1 decreased AQP4 (encoding aquaporin 4) expression to attenuate OGD/R injury. TUG1 could interact directly with miR-145, and down-regulation of miR-145 could efficiently reverse the function of TUG1 siRNA on AQP4 expression. Finally, the TUG1 shRNA reduced the infarction area and cell apoptosis in I/R mouse brains in vivo. In summary, our results suggested that lncRNA TUG1 may function as a competing endogenous RNA (ceRNA) for miR-145 to induce cell damage, possibly providing a new therapeutic target in cerebral ischaemia/reperfusion injury.

Propofol exerts anti-hepatocellular carcinoma by microvesicle-mediated transfer of miR-142-3p from macrophage to cancer cells.

OBJECTIVE: We previously confirmed that propofol directly inhibited the viability, proliferation, and invasiveness of hepatocellular carcinoma cells in vitro. In this study, we investigated the mechanism underlying the anti-HCC effects of propofol. METHODS: In vivo antitumor activity was investigated in tumor-bearing mice following an intraperitoneal injection of propofol, with or without clodrolip. The co-culture system was used to verify that miR-142-3p was transported from macrophages to HCC cells. A miR-142-3p inhibitor was used to down-regulate the expression of miR-142-3p. RESULTS: Propofol drastically inhibited tumor growth in tomor-bearing mice through macrophage activation, and stimulated tumor-associated macrophages (TAMs) to secrete microvesicles (MVs), which delivered miR-142-3p to HCC cells, resulting in the inhibition of HCC cell invasion. In addition, MVs collected from the plasma of the tumor-bearing mice injected with propofol suppressed tumor growth. More importantly, down-regulation of the expression miR-142-3p reversed the effect of propofol on HCC cell migration. CONCLUSIONS: This study reveals a novel role for propofol in the inhibition of HCC through MV-mediated transfer of miR-142-3p from macrophages to cancer cells in vivo.

Optimizing Deep Learning Models with Improved BWO for TEC Prediction.

The prediction of total ionospheric electron content (TEC) is of great significance for space weather monitoring and wireless communication. Recently, deep learning models have become increasingly popular in TEC prediction. However, these deep learning models usually contain a large number of hyperparameters. Finding the optimal hyperparameters (also known as hyperparameter optimization) is currently a great challenge, directly affecting the predictive performance of the deep learning models. The Beluga Whale Optimization (BWO) algorithm is a swarm intelligence optimization algorithm that can be used to optimize hyperparameters of deep learning models. However, it is easy to fall into local minima. This paper analyzed the drawbacks of BWO and proposed an improved BWO algorithm, named FAMBWO (Firefly Assisted Multi-strategy Beluga Whale Optimization). Our proposed FAMBWO was compared with 11 state-of-the-art swarm intelligence optimization algorithms on 30 benchmark functions, and the results showed that our improved algorithm had faster convergence speed and better solutions on almost all benchmark functions. Then we proposed an automated machine learning framework FAMBWO-MA-BiLSTM for TEC prediction, where MA-BiLSTM is for TEC prediction and FAMBWO for hyperparameters optimization. We compared it with grid search, random search, Bayesian optimization algorithm and beluga whale optimization algorithm. Results showed that the MA-BiLSTM model optimized by FAMBWO is significantly better than the MA-BiLSTM model optimized by grid search, random search, Bayesian optimization algorithm, and BWO.

Improved Colony Predation Algorithm Optimized Convolutional Neural Networks for Electrocardiogram Signal Classification.

Recently, swarm intelligence algorithms have received much attention because of their flexibility for solving complex problems in the real world. Recently, a new algorithm called the colony predation algorithm (CPA) has been proposed, taking inspiration from the predatory habits of groups in nature. However, CPA suffers from poor exploratory ability and cannot always escape solutions known as local optima. Therefore, to improve the global search capability of CPA, an improved variant (OLCPA) incorporating an orthogonal learning strategy is proposed in this paper. Then, considering the fact that the swarm intelligence algorithm can go beyond the local optimum and find the global optimum solution, a novel OLCPA-CNN model is proposed, which uses the OLCPA algorithm to tune the parameters of the convolutional neural network. To verify the performance of OLCPA, comparison experiments are designed to compare with other traditional metaheuristics and advanced algorithms on IEEE CEC 2017 benchmark functions. The experimental results show that OLCPA ranks first in performance compared to the other algorithms. Additionally, the OLCPA-CNN model achieves high accuracy rates of 97.7% and 97.8% in classifying the MIT-BIH Arrhythmia and European ST-T datasets.

Effect of Intraoperative Intravenous Lidocaine on Postoperative Delirium in Elderly Patients with Hip Fracture: A Prospective Randomized Controlled Trial.

Purpose: This study was performed to evaluate the effects of intraoperative intravenous lidocaine on postoperative delirium in elderly patients with hip fracture. Patients and methods: In total, 100 elderly patients undergoing hip fracture surgery were randomized to the lidocaine group (Group L) or saline (control) group (Group C). Before anesthetic induction, Group L received lidocaine at 1 mg/kg for more than 10 minutes followed by continuous infusion at 1.5 mg/kg/h until the end of surgery. Group C received normal saline, and the injection methods were consistent with those in Group L. General anesthesia was induced with propofol, sufentanil, and cis-atracurium. Anesthesia was maintained by propofol and remifentanil. The primary outcome was the incidence of postoperative delirium in the first 7 postoperative days. The secondary outcomes included the severity of delirium, onset and duration of delirium, emergence agitation, adverse events, total propofol dose, intraoperative opioid dosage, length of post-anesthesia care unit stay, extubation time, and patient satisfaction with postoperative pain management. Results: All 100 patients completed the study. The incidence of postoperative delirium was lower in Group L than in Group C (14% vs 36%, P = 0.011). The delirium severity scores were lower in Group L (3 [3-4]) than in Group C (4 [4-5]) (P = 0.017). In addition, the incidences of hypertension, tachycardia, and emergence agitation were significantly lower in Group L than in Group C. No cases of local anesthetic toxicity occurred in either group. Conclusion: Patients received lidocaine at 1 mg/kg for more than 10 minutes followed by continuous infusion at 1.5 mg/kg/h until the end of surgery, which can reduce the incidence of postoperative delirium in elderly patients undergoing hip fracture. In addition, the used regimen of lidocaine would not increase the risk of local anesthetic toxicity.

Clinical effect of different doses of ciprofol for induction of general anesthesia in elderly patients: A randomized, controlled trial.

Ciprofol is a newly developed intravenous anesthetic agent with improved pharmacokinetic properties. Compared to propofol, ciprofol exhibits stronger binding to the GABAA receptor and elicits a greater enhancement of GABAA receptor-mediated neuronal currents in vitro. The aims of the present clinical trials were to examine the safety and efficacy of different doses of ciprofol for induction of general anesthesia in elderly patients. A total of 105 elderly patients undergoing elective surgery were randomized, in a 1:1:1 ratio, to receive one of three sedation regimens: (1) the C1 group (0.2 mg/kg ciprofol), (2) the C2 group (0.3 mg/kg ciprofol), (3) the C3 group (0.4 mg/kg ciprofol). The primary outcome was the incidence of various adverse events, including hypotension, hypertension, bradycardia, tachycardia, hypoxemia, and injection pain. The secondary outcomes of efficacy were the success rate of general anesthesia induction, the time to anesthesia induction, and the frequency of remedial sedation was recorded in each group. Adverse events occurred in 13 patients (37%) in group C1, 8 patients (22%) in group C2, and 24 patients (68%) in group C3. Compared with group C2, the total incidence of adverse events was significantly higher in group C1 and group C3 (p < .001).The success rate of general anesthesia induction in the three groups was 100%. Compared with group C1, the frequency of remedial sedation was significantly lower in group C2 and group C3. The outcomes demonstrated that ciprofol at a dose of 0.3 mg/kg has good safety and efficacy in the induction of general anesthesia in elderly patients. Overall, ciprofol is a new and viable option for the induction of general anesthesia in elderly patients undergoing elective surgery.

Efficacy and Safety of Ciprofol for Sedation/Anesthesia in Patients Undergoing Hysteroscopy: A Randomized, Parallel-Group, Controlled Trial.

Objective: To compare the efficacy and safety of ciprofol and propofol for sedation during hysteroscopy. Methods: A total of 149 patients undergoing hysteroscopy were randomly assigned to a ciprofol (Group C) or propofol group (Group P). All cases received intravenous sufentanil 0.1 µg/kg for analgesic preconditioning. Group C received an induction dose of ciprofol 0.4 mg/kg and a maintenance dosage of 0.6-1.2 mg/kg/h to maintain BIS value between 40-60. In Group P, propofol was started at 2.0 mg/kg and then maintained at 3.0-6.0 mg/kg/h. The primary outcome was the successful rate of hysteroscopy. Secondary outcomes included the change of hemodynamic, respiratory adverse events, injection pain, body movement, recovery time, anesthetist's satisfaction, time of disappearance of the eyelash reflex and the incidence of nausea and vomiting. Results: The success rate of hysteroscopy in each group was 100%. After drug administration, the incidence of hypotension in Group C was much lower than that in Group P (P< 0.05). The incidence of respiratory adverse events in Group C (4.0%) was much lower than that in Group P (31.1%) (P< 0.05). The incidence of injection pain and body movement in Group C was significantly lower than that in Group P (P< 0.05). The mean eyelash reflex disappearance time was less than 3 minutes in both groups. There was no statistically significant difference between the two groups in awakening times, anesthetist's satisfaction and the incidence of nausea and vomiting. No serious adverse events occurred in any patients. Conclusion: Ciprofol proved to be a safer alternative to propofol for anesthesia during hysteroscopy. In comparison to propofol, ciprofol does not cause injection pain, exerts less impact on hemodynamics, and results in less respiratory depression.

[Anesthetic management of Stanford type A aortic dissection operation].

OBJECTIVE: To explore the anesthetic management experiences of patients with Stanford A aortic dissection undergoing surgical treatment through moderate or deep hypothermia circulatory arrest (DHCA). METHODS: From June 2008 to December 2011, a total of 77 patients undergoing surgical treatment of Stanford A aortic dissection was recruited. RESULTS: Cardiopulmonary bypass (CPB) was established under general anesthesia in all patients. The procedures included moderate hypothermia (n = 51) and DHCA (n = 26). The total surgical duration was 152 - 600 (292 ± 91) min, CPB time 38 - 310 (128 ± 43) min and aortic cross-clamp time 31 - 169 (87 ± 26) min. The time of circulatory arrest under deep hypothermia was 20 - 113 (41 ± 19) min in 26 patients. Among 77 patients, there were 5 intraoperative and 7 postoperative fatalities. The remained 65 patients were discharged postoperatively and received a regular outpatient follow-up. None of them died or required reoperation. CONCLUSION: Surgical treatment is appropriate and efficient for the patients with Stanford A aortic dissection. During surgery, the keys of preventing neurological complications are blood volume monitoring and blood protection.

An efficient rotational direction heap-based optimization with orthogonal structure for medical diagnosis.

The heap-based optimizer (HBO) is an optimization method proposed in recent years that may face local stagnation problems and show slow convergence speed due to the lack of detailed analysis of optimal solutions and a comprehensive search. Therefore, to mitigate these drawbacks and strengthen the performance of the algorithm in the field of medical diagnosis, a new MGOHBO method is proposed by introducing the modified Rosenbrock's rotational direction method (MRM), an operator from the grey wolf optimizer (GWM), and an orthogonal learning strategy (OL). The MGOHBO is compared with eleven famous and improved optimizers on IEEE CEC 2017. The results on benchmark functions indicate that the boosted MGOHBO has several significant advantages in terms of convergence accuracy and speed of the process. Additionally, this article analyzed the diversity and balance of MGOHBO in detail. Finally, the proposed MGOHBO algorithm is utilized to optimize the kernel extreme learning machines (KELM), and a new MGOHBO-KELM is proposed. To validate the performance of MGOHBO-KELM, seven disease diagnostic questions were introduced for testing in this work. In contrast to advanced models such as HBO-KELM and BP, it can be concluded that the MGOHBO-KELM model can achieve optimal results, which also proves that it has practical significance in solving medical diagnosis problems.

The Effects of Bispectral Index-Guided Anesthesia on Postoperative Delirium in Elderly Patients: A Systematic Review and Meta-Analysis.

OBJECTIVE: Postoperative delirium (POD) is a form of delirium that affects patients who have undergone surgical procedures and anesthesia, usually peaking between 1 and 3 days after their operation. The aim of this meta-analysis was to determine whether monitoring of depth of anesthesia may influence the incidence of POD. METHODS: A systematic literature search was conducted on studies that reported POD in elderly patients (>60 years old) who underwent surgery. This meta-analysis was carried out using random-effects model. RESULTS: Compared with control group, intraoperative bispectral index (BIS) monitoring reduced POD (odds ratio 1.32, 95% confidence interval 1.11-1.57, P = 0.001, I2 = 51%). In the mixed-surgery group, compared with the control group, BIS monitoring decreased the incidence of POD (odds ratio 1.24, 95% confidence interval 1.07-1.44, P = 0.004, I2 = 61%). There was also no significant difference in the incidence of POD among patients who underwent cardiac, colon, and orthopedic surgeries. CONCLUSIONS: BIS monitoring during surgery can reduce the incidence of POD in elderly patients. Whether BIS monitoring may reduce the incidence of POD in a single type of surgery needs further study.

The mechanism of sevoflurane post-treatment alleviating hypoxic-ischemic encephalopathy by affecting histone methyltransferase G9a in rats.

Hypoxic-ischemic encephalopathy (HIE) is recognized as the main cause of neonatal death, and efficient treatment strategies remain limited. This study aims to investigate the mechanism of sevoflurane (SF) post-treatment in alleviating HIE in rats. The HIE rat model and oxygen-glucose deprivation (OGD) cell model were established, and adeno-associated virus (AAV)-histone-lysine N-methyltransferase EHMT2 (G9a) was transfected after SF treatment. The learning and memory ability and the levels of nerve growth factor (NGF)/brain-derived neurotrophic factor (BDNF) were evaluated and determined. The levels of G9a/histone H3 lysine 9 dimethylation (H3K9me2) and the enrichment level of H3K9me2 in the promoter region of BDNF gene were analyzed. After SF post-treatment, the neurons in cerebral cortex, the learning and memory skills and the contents of NGF/BDNF were increased, while the apoptosis and G9a/H3K9me2 levels were reduced. After overexpression of G9a in vitro/vivo, the enrichment levels of H3K9me2 in the promoter region of BDNF were increased, the levels of BDNF were decreased, the neurons were damaged and the learning and memory abilities of HIE rats were impaired. The conclusion is that SF post-treatment can promote the expression of BDNF by inhibiting H3K9me2 on the BDNF gene promoter and inhibiting G9a, thus alleviating HIE in rats.

Effects of GLUT4 expression on insulin resistance in patients with advanced liver cirrhosis.

Decreased glucose tolerance and diabetes are frequently observed in advanced liver cirrhosis patients and may be related to insulin resistance. Glucose transporter-4 (GLUT4), one of the most important glucose transporters, plays a key role in the development of type 2 diabetes. In order to study the mechanism of insulin resistance in liver cirrhosis patients, we measured the insulin sensitivity index and determined the GLUT4 protein and mRNA contents of skeletal muscle by Western blotting and reverse transcription-polymerase chain reaction (RT-PCR), respectively, in normal people and liver cirrhosis patients. The results showed that the levels of glucose, insulin, and C-peptide in two liver cirrhosis groups were higher and the insulin sensitivity index lower than those of the normal control group. The sensitivity of insulin may decrease with the decline of liver function. However, the contents of GLUT4 protein and mRNA in patients with advanced liver cirrhosis were similar to those of normal controls. In conclusion, insulin resistance is observed in patients with advanced liver cirrhosis but may not be correlated with the skeletal contents of GLUT4 protein and mRNA.