Oxycodone vs. tramadol in postoperative parent-controlled intravenous analgesia in children: a prospective, randomized, double-blinded, multiple-center clinical trial.

BACKGROUND: Management of acute postoperative pain is one of the major challenges in pediatric patients. Oral oxycodone has shown good pain relief in postoperative pain relief in children, but no studies have investigated intravenous oxycodone in this context. OBJECTIVE: whether oxycodone PCIA can provide adequate and safe postoperative pain relief, in comparison to tramadol as reference opioid drug. DESIGN: a randomized, double-blind, parallel, multi-center clinical trial. SETTING: five university medical centers and three teaching hospitals in China. PARTICIPANTS: patients aged 3-month-old to 6-year-old undergoing elective surgery under general anesthesia. INTERVENTION: patients were randomly allocated to either tramadol (n = 109) or oxycodone (n = 89) as main postoperative opioid analgesic. Tramadol or oxycodone were administered with a loading dose at the end of surgery (1 or 0.1 mg.kg-1, respectively), then with a parent-controlled intravenous device with fixed bolus doses only (0.5 or 0.05 mg.kg-1, respectively), and a 10-min lockout time. OUTCOMES: the primary outcome was adequate postoperative pain relief, defined as a face, legs, activity, cry, and consolability (FLACC) score < 4/10 in the post-anesthesia care unit (PACU), with no need for an alternative rescue analgesia. FLACC was measured 10 min after extubation then every 10 min until discharge from PACU. Analgesia was currently conducted with the boluses of either tramadol or oxycodone if FLACC was ≥ 3, up to three bolus doses, after what rescue alternative analgesia was administered. RESULTS: tramadol and oxycodone provided a similar level of adequate postoperative pain relief in PACU and in the wards. No significant differences were either noted for the raw FLACC scores, the bolus dose demand in PACU, the time between the first bolus dose and discharge from PACU, analgesic drug consumption, bolus times required in the wards, function activity score, or the parents' satisfaction. The main observed side effects in both groups were nausea and vomiting, with no difference between groups. However, patients in the oxycodone group showed less sedation levels and had a shorter stay in the PACU, compared with the tramadol group. CONCLUSIONS: an adequate postoperative analgesia can be achieved with intravenous oxycodone, this with less side effects than tramadol. It can therefore be a choice for postoperative pain relief in pediatric patients. TRIAL REGISTRATION: The study was registered at www.chictr.org.cn (Registration number: ChiCTR1800016372; date of first registration: 28/05/2018; updated date:06/01/2023).

The role of Bag2 in neurotoxicity induced by the anesthetic sevoflurane.

Sevoflurane is the most commonly used general anesthetic in pediatric patients. But preclinical studies indicate that sevoflurane could have neurotoxicity in newborn and old animals, and this raises concern regarding its safety. In this study, we explored the potential mechanisms of sevoflurane-induced neurotoxicity in human SH-SY5Y neuronal cells. We showed that prolonged exposure to 2% sevoflurane caused a significant increase in the Bag family protein Bag2 in a time- and dose-dependent manner. We investigated the possible role of Bag2 upon exposure to sevoflurane by silencing Bag2 in neuronal cells. Knockdown of Bag2 caused increased overall reactive oxygen species (ROS) and generation of lipid peroxidation products 4-hydroxynonenal (4-HNE). Upon sevoflurane exposure, Bag2-silent cells have reduced glutathione (GSH) and glutathione peroxidase activity. Under the sevoflurane treatment, Bag2-deficient cells have reduced mitochondrial membrane potential (MMP) and adenosine triphosphate (ATP) production, while knockdown cells have less viability and higher lactic dehydrogenase (LDH) release as well as a higher percentage of apoptotic cells. The knockdown cells also had higher levels of mitochondrial cytochrome C release, a higher ratio of Bax/Bcl-2 and increased caspase cleavage by sevoflurane. Overall, our data support an important role of Bag2 in sevoflurane-induced neurotoxicity.

High-Temperature Chlorination of Nickel Oxide Using Calcium Chloride.

Attempts have been made to extract nickel from ores and nickel-containing wastes using the chlorination method. However, the use of gaseous chlorinating agents is limited due to their toxicity. High-temperature chlorination of nickel oxide using calcium chloride is analyzed in this study. The volatilization percentage is positively correlated to temperature and CaCl2 dosage and negatively correlated to oxygen partial pressure. The apparent activation energy is calculated to be 142.91 kJ/mol, between 1173 K and 1323 K, which suggests that the high-temperature chlorination of nickel oxide using calcium chloride is controlled by a chemical reaction.

Analgesic Effects and Safety of Dexmedetomidine Added to Nalbuphine or Sufentanil Patient-Controlled Intravenous Analgesia for Children After Tonsillectomy Adenoidectomy.

Tonsillectomy is a frequently performed surgical procedure in children, requiring post-operative analgesia. This study evaluated the efficacy and safety of nalbuphine or sufentanil combined with dexmedetomidine for patient-controlled intravenous analgesia (PCIA) after pediatric tonsillectomy adenoidectomy. A total of 400 patients undergoing tonsillectomy with and without adenoidectomy were included in the study. Patients received a PCIA pump (0.5 mg/kg nalbuphine, 2 µg/kg dexmedetomidine and 0.9% sodium chloride to a total volume of 100 ml) for postoperative pain management were classified into Group ND (n = 200). Patients received a PCIA pump (2 µg/kg sufentanil, 2 µg/kg dexmedetomidine and 0.9% sodium chloride to a total volume of 100 ml) for postoperative pain management were classified into Group SD (n = 200). More stable hemodynamic changes were noted in Group ND than Group SD from 1 h to 48 h after operation. At 6, 12, 24, and 48 h after operation, the children in Group ND had higher Ramsay sedation scores than those in Group SD. The times to push the PCIA button in Group ND and Group SD were 2.44 ± 0.74 and 2.62 ± 1.00, showing significant differences (p = 0.041). The VASR scores of children in Group ND were significantly lower within 6, 12, and 24 h than those in Group SD (p < 0.05). The VASC scores of children in Group ND were significantly lower within four time points (2, 6, 12, and 24 h) than those in Group SD (p < 0.05). At 1st day after surgery, the children in Group ND had lower levels of serum ACTH, IL-6, and COR levels than those in Group SD (p < 0.001). The incidence rates of nausea and vomiting, and pruritus were significantly higher in Group SD than Group ND (5.00% vs. 11.00%, p = 0.028; 1.00% vs. 4.50%, p = 0.032). The total incidence rate of adverse reactions was significantly higher in Group SD than Group ND (15.00% vs. 31.00%, p = 0.0001). The study demonstrated that dexmedetomidine added to nalbuphine PCIA enhanced the analgesic effects, attenuated the postoperative pain, and reduced the stress response after pediatric tonsillectomy adenoidectomy.

A survival analysis based volatility and sparsity modeling network for student dropout prediction.

Student Dropout Prediction (SDP) is pivotal in mitigating withdrawals in Massive Open Online Courses. Previous studies generally modeled the SDP problem as a binary classification task, providing a single prediction outcome. Accordingly, some attempts introduce survival analysis methods to achieve continuous and consistent predictions over time. However, the volatility and sparsity of data always weaken the models' performance. Prevailing solutions rely heavily on data pre-processing independent of predictive models, which are labor-intensive and may contaminate authentic data. This paper proposes a Survival Analysis based Volatility and Sparsity Modeling Network (SAVSNet) to address these issues in an end-to-end deep learning framework. Specifically, SAVSNet smooths the volatile time series by convolution network while preserving the original data information using Long-Short Term Memory Network (LSTM). Furthermore, we propose a Time-Missing-Aware LSTM unit to mitigate the impact of data sparsity by integrating informative missingness patterns into the model. A survival analysis loss function is adopted for parameter estimation, and the model outputs monotonically decreasing survival probabilities. In the experiments, we compare the proposed method with state-of-the-art methods in two real-world MOOC datasets, and the experiment results show the effectiveness of our proposed model.

Elevating miR-378 strengthens the isoflurane-mediated effects on myocardial ischemia-reperfusion injury in mice via suppression of MAPK1.

OBJECTIVE: Myocardial ischemia reperfusion (MI/RI) stresses the pathological process of progressive aggravation of tissue damage in ischemic myocardium. Isoflurane (ISO) is cardioprotective in MI/RI. Thus, this work aimed to identify the mechanism of isoflurane (ISO) post-treatment in MI/RI by regulating microRNA-378 (miR-378) and mitogen-activated protein kinase 1 (MAPK1). METHODS: A MI/RI model was established by ligating the left anterior descending coronary artery in mice. The modeled mice were injected with ISO or miR-378 or MAPK1 to define their roles in hemodynamics, myocardial injury, cell apoptosis and inflammatory infiltration of mice. CD45, miR-378 and MAPK1 levels were detected. Dual luciferase reporter gene assay was utilized for detection of the targeting connection of miR-378 and MAPK1. RESULTS: Reduced miR-378 and elevated MAPK1 existed in MI/RI. ISO elevated miR-378 to target MAPK1. ISO improved hemodynamics and myocardial injury, reduced apoptosis rate and inflammatory infiltration in MI/RI mice. Up-regulated miR-378 further enhanced the protective effect of ISO on MI/RI mice. Depleting MAPK1 reversed the effects of suppressed miR-378 on MI/RI. CONCLUSION: This study highlights that elevating miR-378 strengthens the isoflurane-mediated effects on MI/RI in mice via suppressing MAPK1, which provides a potential treatment for MI/RI.

The autophagy-related genes Beclin1 and LC3 in the prognosis of pancreatic cancer.

PURPOSE: To investigate the role of the autophagy-related genes Beclin1 and LC3 in the prognosis of pancreatic cancer. METHODS: A total of 86 pancreatic cancer tissues and 84 paired, adjacent normal pancreatic tissues were collected from 86 patients who underwent pancreatic resection surgery in our hospital from January 2009 to August 2011. Demographic data including age, gender, family cancer history, and clinic-pathological characteristics, including tumor diameter, differential, TNM staging and lymphatic metastasis were collected. The expressions of Beclin1 and LC3 were determined using both immunohistochemistry (IHC) and RT-qPCR. RESULTS: The expression levels of both Beclin1 and LC3 mRNA and proteins were significantly up-regulated in the tumor tissues compared with the normal tissues. Higher expressions of Beclin1 and LC3 were found in the tumor tissues of patients with TNM stages III~IV, patients with lymphatic metastasis, and patients who died. Meanwhile Beclin1 and LC3 correlated with TNM stage, differential condition, and the patients' lymphatic metastasis rates. A survival analysis showed that patients with low expressions of Beclin1 and LC3 had longer survival times, and both the Beclin1 and LC3 genes were independent risk factors for 5-year mortality in pancreatic cancer patients. CONCLUSION: The Beclin1 and LC3 genes correlate with the tumor stage, metastasis conditions, and pancreatic cancer patients' mortality.

High-Level Production of DNA-Specific Endonuclease AsEndI with Synonymous Codon and its Potential Utilization for Removing DNA Contamination.

Endonuclease I is a widely distributed periplasmic or extracellular enzyme. A method for the high-level production of recombinant AsEndI (endonuclease I from Aliivibrio salmonicida) in Escherichia coli with secretion expression is investigated. The coding sequence of AsEndI gene was assembled according to the E. coli codon usage bias, and AsEndI was expressed in the periplasm of E. coli TOP10 with a C-terminal 6× His-tagged fusion. The recombinant AsEndI (His-AsEndI) was purified by Ni-NTA resin with a yield of 1.29 × 107 U from 1-L LB medium. His-AsEndI could be classified into Ca2+/Mg2+-dependent nucleases and showed highest nuclease activity to dsDNA at pH 8.0 and 37 °C. His-AsEndI is highly active in a broad range of salt concentration range up to 1.0 M with optimal NaCl concentration at 0.4 M. His-AsEndI can effectively remove DNA contamination in RNA sample or in PCR reagents to the level that cannot be detected by highly sensitive nested PCR and without adverse effects on the subsequent PCR reaction. His-AsEndI can remove DNA contamination at high salt conditions, especially for the DNA that may be shielded by DNA-binding protein at low salt conditions.

Effects of dexmedetomidine post­treatment on BDNF and VEGF expression following cerebral ischemia/reperfusion injury in rats.

Brain­derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) serves a significant role in neural protection by activating the phosphatidylinositol 3­kinase (PI3K)/Akt signaling pathway, which also was associated with the neuroprotective the treatment with dexmedetomidine (DEX). The present study aimed to further explore whether treatment with DEX post­IR increased the expression level of BDNF and VEGF in the rat brain. A total of 30 healthy, clean male Wistar rats were randomly divided into 3 experimental groups: Control group, ischemia/reperfusion (I/R) group and DEX treatment group. Subsequently, BDNF and VEGF mRNA and protein expression levels were analyzed. The results indicated that the mRNA expression levels of BDNF and VEGF were higher in the I/R and DEX groups compared with expression levels in the Control group at 6 h and 1 day post­treatment; the levels of BNDF mRNA expression were higher in the DEX group compared with the I/R group. The levels of BDNF and VEGF protein expression in the I/R and DEX groups were also significantly higher compared with those in the Control group. I/R surgery significantly increased the expression of BDNF and VEGF protein DEX group at 6 h, day 1 and day 3 compared with expression levels in the I/R group. Results from the present study indicated that post­surgical treatment with DEX may increase the expression of BDNF and VEGF following I/R, which may serve a role in nerve protection.

Polyunsaturated fatty acids and acetoacetate downregulate the expression of the ATP-binding cassette transporter A1.

Low HDL cholesterol is a frequent cardiovascular risk factor in diabetes. Because of its pivotal role for the regulation of HDL plasma levels, we investigated in vivo and in vitro regulation of the ATP-binding cassette transporter A1 (ABCA1) by insulin and metabolites accumulating in diabetes. Compared with euglycemic control mice, ABCA1 gene expression was severely decreased in the liver and peritoneal macrophages of diabetic mice. Treatment with insulin restored this deficit. Incubation of cultivated HepG2 hepatocytes and RAW264.7 macrophages with unsaturated fatty acids or acetoacetate, but not with insulin, glucose, saturated fatty acids, or hydroxybutyrate, downregulated ABCA1 mRNA and protein. The suppressive effect of unsaturated fatty acids and acetoacetate became most obvious in cells stimulated with oxysterols or retinoic acid but was independent of the expression of the thereby regulated transcription factors liver-X-receptor alpha (LXRalpha) and retinoid-X-receptor alpha (RXRalpha), respectively. Unsaturated fatty acids and acetoacetate also reduced ABCA1 promotor activity in RAW264.7 macrophages that were transfected with a 968-bp ABCA1 promotor/luciferase gene construct. As the functional consequence, unsaturated fatty acids and acetoacetate inhibited cholesterol efflux from macrophages. Downregulation of ABCA1 by unsaturated fatty acids and acetoacetate may contribute to low HDL cholesterol and increased cardiovascular risk of diabetic patients.

Effect of orthodontic force on inflammatory periodontal tissue remodeling and expression of IL-6 and IL-8 in rats.

OBJECTIVE: To investigate effect of orthodontic force on inflammatory periodontal tissue remodeling and expression of IL-6 and IL-8 in rats. METHODS: Eighty SD rats were randomly divided into 4 groups, blank control group (group A) with 5 rats, treatment normal group (group B) with 25 rats, inflammation control group (group (group C) with 25 rats, inflammation treatment group (group D) with 25 rats. Immunohistochemistry and histomorphometric analysis was performed to measure the expression of IL-6, IL-8 and the first molar to the recent movement in the distance. RESULTS: The expression of IL-8 reached a maximum on day 5 and declined thereafter in group B; the expression of IL-6 reached a maximum on day 5 in group B. The expression of IL-6 and IL-8 was gradually weakened with time in group C. The expression of IL-6 and IL-8 were high, and reached a maximum on day 5 and declined thereafter in group D. AD of positive cells in group D were higher than group B at each time point (P<0.05). The time which 0.49 N orthodontic force was loaded was longer, orthodontic tooth movement distance was greater. Movement distance in group D were longer than group B (P<0.05). CONCLUSIONS: Orthodontic force as well as inflammatory stimulus can evoke the expression of IL-6 and IL-8. Under the combined effects of inflammation and orthodontic force, the expression of IL-6, IL-8 will increase.