Nalbuphine in Pediatric Emergence Agitation Following Cochlear Implantation: A Randomized Trial.

Background: To investigate the effects of nalbuphine on emergency agitation (EA), which affects up to 80% of the children following otolaryngology procedures, in children undergoing cochlear implantation. Methods: A prospective double-blinded randomized controlled clinical trial was conducted between November 2020 and October 2022. Eligible children, aged 6 months to 3 years old, were randomly assigned to either 0.1 mg/kg, 0.15 mg/kg, 0.2 mg/kg nalbuphine or 0.9% saline groups. EA was defined by the Pediatric Anesthesia Emergence Delirium (PAED) score ≥10. Extubation time, post-anesthesia care unit (PACU) length of stay, severe EA (PAED ≥ 15), peak PAED score, the Faces, Legs, Activity, Cry, and Consolability (FLACC) scale, Ramsay sedation score, and adverse events were also recorded. Results: A total of 104 children were enrolled, with 26 children in each group. Nalbuphine significantly reduced the EA occurrence from 73.1% in the saline group to 38.5%, 30.8%, and 26.9% in the 0.1 mg/kg, 0.15 mg/kg, and 0.2 mg/kg nalbuphine groups, respectively (P < 0.001), without affecting the extubation time and PACU length of stay. More children (34.6%) in the 0.9% saline group experienced severe EA. Higher dose nalbuphine (0.15 mg/kg, 0.2 mg/kg) showed lower peak PAED score, better analgesia and sedation effect compared with 0.1 mg/kg nalbuphine and saline groups. However, 0.2mg/kg nalbuphine caused undesired over-sedation in two (7.7%) children. No other adverse events were reported. Conclusion: Young children undergoing cochlear implantation surgery were at a high risk of EA and postoperative pain, while 0.2 mg/kg nalbuphine might be an ideal candidate for EA and pain prevention when used under close monitoring. Trial Registration: ChiCTR2000040407.

Dysfunction of astrocytic glycophagy exacerbates reperfusion injury in ischemic stroke.

Glycophagy has evolved from an alternative glycogen degradation pathway into a multifaceted pivot to regulate cellular metabolic hemostasis in peripheral tissues. However, the pattern of glycophagy in the brain and its potential therapeutic impact on ischemic stroke remain unknown. Here, we observed that the dysfunction of astrocytic glycophagy was caused by the downregulation of the GABA type A receptor-associated protein like 1 (GABARAPL1) during reperfusion in ischemic stroke patients and mice. PI3K-Akt pathway activation is involved in driving GABARAPL1 downregulation during cerebral reperfusion. Moreover, glycophagy dysfunction-induced glucosamine deficiency suppresses the nuclear translocation of specificity protein 1 and TATA binding protein, the transcription factors for GABARAPL1, by decreasing their O-GlcNAcylation levels, and accordingly feedback inhibits GABARAPL1 in astrocytes during reperfusion. Restoring astrocytic glycophagy by overexpressing GABARAPL1 decreases DNA damage and oxidative injury in astrocytes and improves the survival of surrounding neurons during reperfusion. In addition, a hypocaloric diet in the acute phase after cerebral reperfusion can enhance astrocytic glycophagic flux and accelerate neurological recovery. In summary, glycophagy in the brain links autophagy, metabolism, and epigenetics together, and glycophagy dysfunction exacerbates reperfusion injury after ischemic stroke.

Differences in the EEG Power Spectrum and Cross-Frequency Coupling Patterns between Young and Elderly Patients during Sevoflurane Anesthesia.

Electroencephalography (EEG) is widely used for monitoring the depth of anesthesia in surgical patients. Distinguishing age-related EEG features under general anesthesia will help to optimize anesthetic depth monitoring during surgery for elderly patients. This retrospective cohort study included 41 patients aged from 18 to 79 years undergoing noncardiac surgery under general anesthesia. We compared the power spectral signatures and phase-amplitude coupling patterns of the young and elderly groups under baseline and surgical anesthetic depth. General anesthesia by sevoflurane significantly increased the spectral power of delta, theta, alpha, and beta bands and strengthened the cross-frequency coupling both in young and elderly patients. However, the variation in EEG power spectral density and the modulation of alpha amplitudes on delta phases was relatively weaker in elderly patients. In conclusion, the EEG under general anesthesia using sevoflurane exhibited similar dynamic features between young and elderly patients, and the weakened alteration of spectral power and cross-frequency coupling patterns could be utilized to precisely quantify the depth of anesthesia in elderly patients.

Percutaneous cortical bone trajectory screw fixation versus traditional open pedicle screw fixation for type A thoracolumbar fractures without neurological deficit.

Retrospective matched-cohort comparative study. Cortical bone trajectory screw (CBT) technique is a new insertion technique in terms of fixation strength and less invasiveness. The purposes of this study were to compare the clinical and radiological outcomes of percutaneous CBT fixation (PCBT) with traditional open posterior pedicle screw fixation (OPPS) technique. Between September 2019 and October 2020, patients undergoing posterior stabilization were matched for age, sex, diagnosis, fractured level, and AO classification. 24 control patients with OPPS were identified and appropriately matched to 24 consecutive patients with PCBT technique. Clinical outcomes and radiographic assessments including vertebral wedge angle (VWA) and sagittal index were recorded and compared between the two groups. Incision length, intraoperative blood loss and hospital stay in the PCBT group were significantly better than the OPPS group (P < 0.05). The VAS scores 5 days after operation for PCBT patients were significantly lower than those for OPPS patients (P = 0.003), but these differences lost significance at last follow-up. There was no significant difference in VWA and sagittal index between OPPS and PCBT group (P > 0.05). While no complications were noted in the PCBT group, there were four cases with complications in the traditional OPPS group. The present study showed that PCBT is a safe and feasible method for the treatment of thoracolumbar fractures without neurological deficits. This new surgical treatment was more minimally invasive, yet yielded equivalent or superior clinical and radiographic outcomes compared to the traditional open pedicle screw fixation surgery.

[Effects of Different Treatment Methods on the Contents of Related Growth Factors Released by Platelet Rich Plasma].

OBJECTIVE: To evaluate the effect of sonication, repeated freeze-thaw cycles, calcium salt solution and their combination on the content of related growth factors (GFs) released by platelet rich plasma (PRP). METHODS: Twenty PRPs from healthy blood donors were divided into 9 groups, including sonication group, freeze-thaw group, calcium gluconate group, calcium chloride group, sonication + calcium gluconate group, sonication + calcium chloride group, freeze-thaw + calcium gluconate group, freeze-thaw + calcium chloride group, and sonication + freeze-thaw group. After PRP activated by above 9 methods, the content of transforming growth factor-ß1 (TGF-ß1), vascular endothelial growth factor (VEGF), and platelet-derived growth factor-BB (PDGF-BB) were detected by ELISA. RESULTS: The platelet concentration of the samples was (966.7±202.6)×109/L. The content of TGF-ß1 in sonication + freeze-thaw group was the highest, while the lowest was in freeze-thaw group. The content of VEGF in freeze-thaw + calcium chloride group was the highest, while the lowest was in calcium gluconate group. The content of PDGF-BB in sonication + freeze-thaw group was the highest, while the lowest was in calcium gluconate group. There was no significant differences in the three GFs between calcium gluconate group and calcium chloride group. CONCLUSION: Among the 9 activated methods of PRP, there is no difference between two calcium salt solutions. And the combination of repeated freeze-thaw cycles and sonication may be the best treatment method to promote PRP to release GFs, while calcium gluconate is the weakest way.

Label-free analytical performances of a peptide-based QCM biosensor for trypsin.

A label-free biosensor was fabricated for the detection of trypsin by using a peptide-functionalized quartz crystal microbalance gold electrode. The synthetized peptide chains were immobilized tightly on the QCM electrode via a self-assembly method, which formed a thin and approximate rigid layer of peptides. The detection signal was achieved by calculating the mass changes on the QCM electrode because the peptide chains could be specifically cleaved in the carboxyl terminuses of arginine and lysine by trypsin. When gold nanoparticles were coupled to the peptide chains, the sensing signal would be amplified 10.9 times. Furthermore, the sensor interface shows a lower resonance resistance change when the peptide chain is immobilized horizontally. Independent detections in parallel on different electrodes have a wide linear range. Under the optimum conditions, the signal-amplified biosensor allowed the measurement of trypsin over the range of 0-750 ng mL-1 with a detection limit of 8.6 ng mL-1. Moreover, for screening the inhibitor of trypsin, the IC50 values were obtained to be 1.85 µg mL-1 for benzamidine hydrochloride and 20.5 ng mL-1 for the inhibitor from soybean.

Surgery Under General Anesthesia Alleviated the Hyperactivity but Had No Effect on the Susceptibility to PND in ADHD Rats.

Background: Attention-deficit hyperactivity disorder (ADHD) is a typical neuropsychiatric disorder characterized by inattention, impulsivity, and hyperactivity, particularly in children. Recent studies demonstrated a close relationship between the development of ADHD and surgery under general anesthesia. However, few studies illustrated if ADHD symptoms changed after surgery. Meanwhile, whether these individuals with natural neural impairment were sensitive to postoperative neurocognitive disorder (PND) still remain unclear. Methods: Spontaneously hypertensive rats (SHR) were utilized as spontaneous ADHD animal model and Wistar-Kyoto (WKY) rats as non-ADHD animal model. We evaluated the variation of neurocognitive function and locomotor activity of the rats undergoing experimental laparotomy with general anesthesia by isoflurane. Neurocognitive function was assessed by fear conditioning test for contextual memory and Morris water maze (MWM) for spatial memory. Depressive-like behavior after surgery was detected by forced swim test, and open-field test and elevated plus maze test were utilized to evaluate locomotor activities and anxiety. Furthermore, we compared electroencephalogram (EEG) signal in ADHD and WKY rats under free-moving conditions. Afterward, c-Fos staining was also utilized to detect the excitatory activity of neurons in these rats to explore the neural mechanism. Results: Locomotor activity of SHR assessed by average speed and number of line crossings in the open-field test decreased 1 week after surgery under general anesthesia, but there was no difference concerning anxiety levels between SHR and WKY rats after surgery. This phenomenon was also paralleled with the change in EEG signal (delta band 0∼3 Hz). Surgery under general anesthesia had no effect on spatial and contextual memory, while it improved spontaneous depression in SHR. The expression of c-Fos was downregulated for at least 1 week in the nucleus accumbens (NAc) area of ADHD rats' brain after surgery. Conclusion: ADHD rats were not sensitive to PND. Surgery with general anesthesia could partly improve the hyperactivity symptom of ADHD rats. This mechanism was related to the suppression of neural activity in the cerebral NAc of ADHD rats induced by general anesthetics.

Hyperhomocysteinemia is key for increased susceptibility to PND in aged mice.

BACKGROUND: Postoperative neurocognitive disorder (PND) is a severe postoperative complication with no effective therapy that affects up to 19-52% of senior patients. Age and surgery type have been identified as risk factors. However, what caused the increased risk in the elderly is poorly understood. METHODS: We utilized a PND model in aged mice undergoing experimental laparotomy with general anesthesia to evaluate the causal relationship between hyperhomocysteinemia and increased PND susceptibility. PND was assessed by Novel Object Tasks, Fear Conditioning Tests, and Barnes Maze Tests. Serum homocysteine (Hcy) as well as vitamin B12 and folate acid levels were tested before, immediately after surgery and from day 1 to day 29 after surgery by ELISA. The effectiveness of preventative strategy including diet supplementation of vitamin B12 + folic acid (Vit B12 + FA) and S-adenosylmethionine (SAM) injection targeting hyperhomocysteinemia were also tested. RESULTS: PND in aged mice lasted for at least 2 weeks after experimental laparotomy, which was not observed in young adult mice. Serum Hcy results indicated a significant correlation between postoperative cognitive performance and perioperative Hcy level. Preoperative supplementation with VB12 and folic acid (FA) in the diet or S-adenosylmethionine (SAM) injection reduced perioperative serum Hcy level and inhibited the development of PND in aged mice. CONCLUSIONS: Serum homocysteine accumulation is a fundamental cause for increased susceptibility of PND in aged mice. Preoperative diet supplementation of VitB12 + FA can effectively reduce PND in aged mice, which may be a promising prophylaxis treatment in clinical settings.

An in vitro study of coagulation properties in refrigerated whole blood and reconstituted whole blood.

OBJECTIVE: Fresh whole blood (WB) has been used in military applications and cardiac surgery. We undertook a study of the coagulation properties of refrigerated WB stored for 21 days and compared them with the properties of reconstituted WB. STUDY DESIGN AND METHODS: Ten WB units were obtained from healthy volunteer donors and stored at 4 ± 2°C. Samples were obtained on Days 1, 2, 4, 6, 8, 10, 14 and 21 from the WB units. Ten units of reconstituted WB were prepared with a ratio of red cells, platelets and plasma of 1:1:1. Tests included complete blood count, electrolyte, routine coagulation, blood coagulation factor and thromboelastography. RESULTS: There was a progressive decline in Hb, WBC, PLT, sodium and coagulation factors but a progressive increase in APTT, PT and potassium in WB. The concentrations of factor (F)V and FVIII as well as FII and FX of WB were higher before Days 4, 2, 8 and 14, respectively, compared with the concentrations of reconstituted WB. The concentrations of FVII, FIX, FXI and FXII in WB were found to be equal to or higher than those in reconstituted WB throughout the course of 21 days. TEG variables in all WB units were normal throughout the course of 10 days. The mean PT and APTT of WB were lower than those of reconstituted WB before Days 14 and 10, respectively. CONCLUSION: This study suggests that the coagulation properties of refrigerated WB were equal to or superior to those of reconstituted WB for a minimum of 10 days.

Improving systemic circulation of paclitaxel nanocrystals by surface hybridization of DSPE-PEG2000.

This paper aims to improve the systemic circulation of paclitaxel (PTX) by modifying nanocrystals with DSPE-PEG 2000. PTX nanocrystals (PNCs) were prepared by an anti-solvent method and DSPE-PEG 2000 was inserted into PNCs by hybridization. The average size of DSPE-PEG-PNCs did not change obviously compared to the naked PNCs, but the negative charge increased after hybridization. The saturated attachment ratio of DSPE-PEG 2000 was 0.4%. In vitro release rate of DSPE-PEG-PNCs was significantly slower than that of PTX solution and the naked PNCs, which indicated that DSPE-PEG 2000 hindered the release of PTX. Moreover, pharmacokinetics results showed that DSPE-PEG-PNCs achieved a higher area-under-the-curve (AUC, 4.43 ±â€¯0.19 mg/L*h) and lower clearance rate (1.08 ±â€¯0.16 L/h/kg) compared to PNCs with an AUC of 2.48 ±â€¯0.18 mg/L*h and a clearance rate of 1.89 ±â€¯0.15 L/h/kg. Therefore, DSPE-PEG-PNCs could have a significant potential in clinical use by improving the systemic circulation of the drug.

Amplified QCM biosensor for type IV collagenase based on collagenase-cleavage of gold nanoparticles functionalized peptide.

The present study develops a rapid, simple and efficient method for the determination of type IV collagenase by using a specific peptide-modified quartz crystal microbalance (QCM). A small peptide (P1), contains a specific sequence (Pro-Gly) and a terminal cysteine, was synthetized and immobilized to the surface of QCM electrode via the reaction between Au and thiol of the cysteine. The peptide bond between proline and glycine can be specific hydrolyzed cleavage by type IV collagenase, which enabled the modified electrode with a high selectivity toward type IV collagenase. The cleaving process caused a frequency change of QCM to give a signal related to the concentration of type IV collagenase. The morphologies of the modified electrodes were characterized by scanning electron microscope (SEM) and the specific hydrolyzed cleavage process was monitored by QCM. When P1 was modified with gold nanoparticles (P1-Au NPs), the signal could be amplified to further enhance the sensitivity of the designed sensor due to the high-mass of the modified Au NPs. Compared the direct unamplified assay, the values obtained for the limit of detection for type IV collagenase was 0.96 ng mL-1, yielding about 6.5 times of magnitude improvement in sensitivity. This signal enhanced peptide based QCM biosensor for type IV collagenase also showed good selectivity and sensitivity in complex matrix.

A novel signal-on photoelectrochemical immunosensor for detection of alpha-fetoprotein by in situ releasing electron donor.

A signal-on photoelectrochemical (PEC) immunosensor was constructed for detecting tumor marker in this work. α-fetoprotein (AFP) was chosen as a model analyte to investigate the prepared procedure and the analytical performance of the exploited sensor. In order to construct the sensor, CdSe QDs were used as photoactive material, biotin conjugated AFP antibody (Bio-anti-AFP) as detecting probe, streptavidin (SA) as signal capturing unit, biotin functionalized apoferritin encapsulated ascorbic acid (Bio-APOAA) as amplification unit, which were assembled onto the electrodes. The sensing strategy was based on in situ enzymatic hydrolysis of Bio-APOAA to release ascorbic acid (AA) as sacrificial electron donor to produce photocurrent. The photocurrent from the immunosensor was monitored as a result of AFP concentrations. The constructed sensing platform displayed high selectivity and good sensitivity for detecting AFP. Under optimal conditions, a wide linear range from 0.001 to 1000ng/mL and a low detection limit of 0.31pg/mL were obtained. The developed immunosensor is expected to be used to determine AFP and other tumor markers in human plasma in clinical laboratories either for pre-cancer screening or cancer monitoring. Moreover, this sensing platform further has the potential to use for the detection of trypsin activity and the corresponding inhibitor-screening.

Quartz crystal microbalance aptasensor for sensitive detection of mercury(II) based on signal amplification with gold nanoparticles.

We show that a short mercury-specific aptamer (MSA) along with gold nanoparticles (Au-NPs) can be used to determine Hg(II) ion by a combination of a QCM-based sensor and a flow system. The MSA binds specifically to Hg(II), and the Au-NPs can amplify the signal to enhance sensitivity. Specifically, the short thiolated MSAs are immobilized on the surface of the QCM as the capture probe, and the MSAs are linked to the Au-NPs as the linking probe. The two components can form a sandwich structure of the T-Hg(II)-T type in the presence of Hg(II) ions. This leads to change in the mass on the QCM and a change in the resonance frequency. Hg(II) can be determined with a detection limit of 0.24 ± 0.06 nM which is better by three orders of magnitude than previous methods. The sensor can be regenerated by disrupting the T-Hg(II)-T base pairs with a solution of cysteine.

The nano-Au self-assembled glassy carbon electrode for selective determination of epinephrine in the presence of ascorbic acid.

Gold nanoparticles were self-assembled to the modified glassy carbon electrode (GC) with cysteamine (CA) to prepare the nano-Au/CA/GC modified electrode. The electrochemical behavior of epinephrine (EP) on the modified electrode was explored with cyclic voltammetry (CV) and differential pulse voltammetry (DPV). Epinephrine gave a pair of redox peaks at E(pa)=0.190 mV and E(pc)=-0.224 mV (versus SCE), respectively. The nano-Au/CA/GC modified electrode shows an excellent electrocatalytic activity for the oxidation of EP. The modified electrode could be used to determine EP in the presence of ascorbic acid (AA). The response of catalytic current with EP concentration shows a linear relation in the range of 1.0 x 10(-7) to 5.0 x 10(-4) mol L(-1) with the correlation coefficient of 0.998. The detection limit is 4.0 x 10(-8) mol L(-1). The modified electrode exhibited a good reproducibility, sensitivity and stability for the determination of EP injection.