G-Quadruplex/Hemin DNAzyme-Functionalized Silver Nanoclusters with Synergistic Antibacterial and Wound Healing Capabilities for Infected Wound Management.

Systematic management of infected wounds requires simultaneous antiinfection and wound healing, which has become the current treatment dilemma. Recently, a multifunctional silver nanoclusters (AgNCs)-based hydrogel dressing to meet these demands is developed. Here a diblock DNA with a cytosine-rich fragment (as AgNCs template) and a guanine-rich fragment (to form G-quadruplex/hemin DNAzyme, termed G4/hemin) is designed, for G4/hemin functionalization of AgNCs. Inside bacteria, G4/hemin can not only accelerate the oxidative release of Ag+ from AgNCs but also generate reactive oxygen species (ROS) via catalase- and peroxidase-mimic activities, which enhance the antibacterial effect. On the other hand, the AgNCs exhibit robust anti-inflammatory and antioxidative activities to switch M1 macrophages into M2 phenotype, which promotes wound healing. Moreover, the hemin is released to upregulate the heme oxygenase-1, an intracellular enzyme that can relieve oxidative stress, which significantly alleviates the cytotoxicity of silver. As a result, such silver-based dressing achieves potent therapeutic efficacy on infected wounds with excellent biosafety.

Constructing Nano-Interlayer Inhibiting Interfacial Degradation toward High-Voltage PEO-Based All-Solid-State Lithium Batteries.

The interfacial instability between PEO-based solid electrolyte (SPE) and high-voltage cathode materials inhibits the longevity of high-energy-density all-solid-state polymer lithium metal batteries (ASSPLBs). Herein, for the first time it is demonstrated, that contact loss caused by gas generation from interfacial side reactions between the high-voltage cathode and solid polymer electrolyte (SPE) can also arise in ASSPLBs. To alleviate the interfacial side reactions, a LiNb0.6Ti0.5O3 (LNTO) layer is well coated on LiNi0.83Co0.07Mn0.1O2 (NCM83), denoted as (CNCM83). The LNTO layer with low electronic conductivity reduces the decomposition drive force of SPE. Furthermore, Ti and Nb in the LNTO layer spontaneously migrate inside the NCM83 surface to form a strong Ti/Nb─O bond, stalling oxygen evolution in high-voltage cathodes. The interfacial degradation phenomena, including SPE decomposition, detrimental phase transition and intragranular cracks of NCM83, and void formation between cathode and SPE, are effectively mitigated by the LNTO layer. Therefore, the growth rate of interfacial resistance (RCEI) decreases from 37.6 Ω h-0.5 for bare NCM83 to 2.4 Ω h-0.5 for CNCM83 at 4.2 V. Moreover, 4.2 V PEO-based ASSPLBs achieve impressive cyclability with high capacity retention of 135 mAh g-1 (75%) even after 300 cycles at 0.5 C.

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).

Effect of neuromuscular block on surgical conditions during laparoscopic surgery in neonates and small infants: A randomised controlled trial.

BACKGROUND: Neuromuscular block (NMB) is routinely used in paediatric and adult anaesthesia to facilitate endotracheal intubation and optimise surgical conditions. However, there are limited data regarding NMB and optimising the conditions for laparoscopic surgery in neonates and small infants. OBJECTIVE: The goal of this study was to determine the effect of NMB on the conditions for laparoscopic surgery in neonates and small infants. DESIGN: A randomised controlled trial. SETTING: Single-centre Children's Hospital, conducted from November 2021 to December 2022. PATIENTS: One hundred and two ASA I-II neonates and small infants aged up to 60 weeks postmenstrual age who were scheduled to undergo an elective laparoscopic Ladd's procedure were included in the study. INTERVENTIONS: Patients were randomised into three groups: no NMB group, shallow NMB group and moderate NMB group. Each group was given different doses of rocuronium to achieve the target depth of NMB. MAIN OUTCOME MEASURES: The primary outcome was the quality of the surgical conditions evaluated with the Leiden-Surgical Rating Scale (L-SRS) by a blinded surgeon. Secondary outcomes included tracheal intubating conditions and adverse events. RESULTS: The percentage of L-SRS scores of 4 or 5 was similar among the three groups at all the assessment times ( P  > 0.05 for each time interval). The distribution of L-SRS scores was also similar among the three groups. There were no significant differences in operating condition scores between the groups at any time interval ( P  > 0.05 for each time interval). The incidence of adverse events during anaesthesia induction was significantly higher in the no NMB group (51.4%) than in the other two groups (13.6% and 14.7%) (adjusted P  = 0.012 and adjusted P  = 0.003). In particular, clinically unacceptable intubation conditions occurred in 12 patients (34.3%) in the no NMB group, significantly more than in the shallow NMB group (6.1%, adjusted P  = 0.012) and moderate NMB group (2.9%, adjusted P  = 0.003). There was no statistically significant difference in the incidence of adverse events in the PACU among the three groups ( P  = 0.103). CONCLUSIONS: The depth of NMB was not associated with superior surgical conditions during laparoscopic surgery, but it was associated with a reduction in adverse events during induction and maintenance of anaesthesia in neonates and small infants. TRIAL REGISTRATION: Registered at www.chictr.org.cn (ChiCTR2100052296).

NLRP3 inflammasome of microglia promotes A1 astrocyte transformation, neo-neuron decline and cognition impairment in endotoxemia.

Infection, predominantly induced by gram-negative bacteria, is a critical health problem and a leading cause of death worldwide. Advance of techniques, such as antibiotics and life-supporting modality, allows a decreasing death rate of patients with infection in recent decades. Nevertheless, infection-associated complications, in particular cognitive dysfunction, largely influence the mortality of patients and the life quality of survivors. However, the effective medicine is still scant due to the poor interpretion of underlying mechanisms. Herein, we determined multiple cytokines of cerebrospinal fluid in mice challenged with various doses of lipopolysaccharides (LPS)-a pathogenic component of gram-negative bacteria, and found that IL-1ß, the downstream of NLRP3 inflammasome, was boosted to a peak extent after a challenge of LPS in high dose. Genetically knockout of Nlrp3 or the downstreams, such as Asc and Gsdmd, dramatically restored LPS-induced cognitive impairment, which was attributed to inhibiting microglia-induced A1 astrocytes and so-caused neo-neuron decline. Taken together, NLRP3 inflammasome of microglia promotes transformation of A1 astrocytes and consequently exacerbates neo-neuron decline, resulting in cognitive impairment after a challenge of LPS. Our study thus discovers a novel understanding in the pathogenesis of LPS-induced cognitive dysfunction, and indicates that NLRP3 inflammasome would be a promising target in the treatment of the syndrome.

Baicalein attenuates acute liver injury by blocking NLRP3 inflammasome.

Infection and/or drug-mediated acute liver injury, the leading cause of lethal liver failure, is a critical health problem worldwide and lacks effective treatment. Here, we used Lipopolysaccharides (LPS)/D-galactosamine (D-gal)-treated primary hepatocytes to screen a natural library that contains 1130 chemicals. Baicalein in the library showed highest inhibitory effects against LPS/D-Gal-induced liver injury. In-vivo study similarly validated the protection of baicalein against dampened liver function and increased lethality after a challenge of LPS/D-Gal. Using a cytometric bead array, we found that IL-1α and IL-1ß, the downstream of NLRP3, had highest reduction among the plasma inflammatory cytokines in LPS/D-Gal-challenged mice after a treatment of baicalein. To determine the target of baicalein and the underlying mechanism, Nlrp3-/-, Gsdmd-/- or WT mice were treated with or without baicalein, IL-1R antibody or recombinant mouse IL-1ß (rmIL-1ß) prior to a challenge of LPS/D-Gal. Deficiency of Nlrp3 or Gsdmd significantly restored LPS/D-Gal-induced acute liver injury and lethality, and further administration of baicalein did not have additive effects. In addition, the inhibition of the downstream by IL-1R antibody phenocopied the knockout of Nlrp3 or Gsdmd. Moreover, a challenge of rmIL-1ß reversed the improvement in Nlrp3-/- mice or the mice treated with baicalein. Taken together, NLRP3 functions as a pivotal promoter in acute liver injury and baicalein attenuates acute liver injury by inhibiting NLRP3 inflammasome.

The effect of dexmedetomidine premedication on postoperative systemic inflammatory response in children undergoing hernia repair surgery: A randomized controlled trial.

BACKGROUND: Surgery results in systemic inflammation, which can affect the central nervous system, leading to changes in mood, emotion, and behavior. Our previous study has shown that compared to midazolam, dexmedetomidine premedication effectively decreased children's postoperative anxiety. AIM: To investigate whether dexmedetomidine infusion before hernia repair alleviates postoperative systemic inflammation in children and whether postoperative anxiety may be associated with postoperative inflammation. METHODS: This prospective double-blind randomized controlled trial was conducted in 120 children scheduled to undergo elective hernia repair. Before anesthesia induction, all children received an intravenous infusion consisted of dexmedetomidine (n = 40; 0.5 µg/g, group D), midazolam (n = 40; 0.08 mg/kg, group M), or normal saline (n = 40; group C). One-way ANOVA with least significant difference multiple comparison test was used for multigroup comparisons of postoperative plasma levels of inflammatory cytokines and m-YPAS scores. Spearman rank correlation tests were used for analyzing m-YPAS scores with postoperative plasma levels of inflammatory cytokines. RESULTS: Plasma levels of tumor necrosis factor-alpha (7.0 ± 1.6 vs. 8.1 ± 1.6, mean difference [95% CI]: 1.19 [0.26-2.11], p = .008) (pg/ml) and of interleukin-6 (1.8 ± 1.2 vs. 3.3 ± 1.6, mean difference [95% CI]: 1.49 [0.74-2.25], p < .001) (pg/ml) and neutrophils-to-lymphocyte ratio (1.0 ± 0.5 vs. 1.5 ± 0.7, mean difference [95% CI]: 0.48 [0.17-0.78], p < .001) were significantly lower in group D than in group C. Furthermore, compared to group M, group D showed significantly lower plasma tumor necrosis factor-alpha levels (7.0 ± 1.6 vs. 7.9 ± 1.9, mean difference [95% CI]: 0.96 [0.04-1.88], p = .04) (pg/ml) and interleukin-6 levels (1.8 ± 1.2 vs. 2.9 ± 1.5, mean difference [95% CI]: 1.06 [0.31-1.81], p = .004) (pg/ml), and neutrophil-to-lymphocyte ratio (1.0 ± 0.5 vs. 1.5 ± 0.6, mean difference [95% CI]: 0.42 [0.11-0.72], p = .004). Anxiety scores at postoperative 2 and 4 h in the three groups positively correlated with plasma levels of proinflammatory cytokines. CONCLUSION: A single preoperative intravenous dexmedetomidine dose in children undergoing same-day surgery reduces postoperative systemic inflammation.

The comparison of dexmedetomidine and midazolam premedication on postoperative anxiety in children for hernia repair surgery: A randomized controlled trial.

BACKGROUND: Perioperative anxiety is common in pediatric patients undergoing surgery. AIMS: The aim of this study was to determine whether an infusion of dexmedetomidine prior to hernia repair in children provides better postoperative anxiety outcomes that a preoperative infusion of midazolam. METHODS: Ninety 6-11-year-old children, who were scheduled to undergo elective hernia repair, were enrolled for this double-blind, randomized controlled trial. Group D (n = 45) received an intravenous infusion of dexmedetomidine (0.5 µg/kg) and Group M (n = 45) received an intravenous infusion of midazolam (0.08 mg/kg) in 20 mL of normal saline for 10 minutes before the induction of anesthesia. Pre- and postoperative scores on the modified Yale Preoperative Anxiety Scale were the main outcomes. Secondary outcomes included systolic blood pressure, diastolic blood pressure, heart rate, and postoperative pain measured on a visual analogue scale and patient satisfaction using a numerical rating scale. RESULTS: Postoperative anxiety in Group D was significantly lower than preoperative anxiety (2 hours postoperatively mean difference [95% CI]: 2.83 [0.87-4.79], P = 0.036, 4 hours postoperatively mean difference [95% CI]: 3.29 [1.39-5.20], P = 0.005). Preoperative and postoperative anxiety in Group M was similar. Anxiety scores in Group D were also significantly lower than anxiety in Group M 2 hours (mean difference [95% CI]: 1.89 [0.52-3.26], P = 0.01) and 4 hours (mean difference [95% CI]: 3.32 [1.98-4.66], P < 0.001) postoperatively. Systolic blood pressure, diastolic blood pressure and heart rate were lower in Group D than in Group M after administration of sedative drugs until children left PACU (SBP mean difference [95% CI]: 13.87 [10.30-17.43], P < 0.001, DBP mean difference [95% CI]: 5.96[3.80-8.11], P < 0.001, HR mean difference [95% CI]: 10.36 [7.58-13.13], P < 0.001). Pain was also significantly lower in Group D than in Group M at 2 hours (median difference [95% CI]: 1 [0.26-1.34], P = 0.004), 4 hours (median difference [95% CI]: 1 [0.31-1.02], P = 0.003), and 1 day (median difference [95% CI]: 0 [0.22-0.76], P = 0.003) postoperatively. Patient satisfaction scores were significantly higher in Group D than in Group M 1 day (median difference [95% CI]: 0 [-0.83 to -0.24], P = 0.006) and somewhat higher 1 week (median difference [95% CI]: 0 [-0.67 to -0.04], P = 0.06) postoperatively. CONCLUSION: Compared with midazolam, a single preoperative intravenous dose of dexmedetomidine appears to provide better postoperative anxiolytic effects for children undergoing same-day surgery.

A Systematic Review of the Measurement Properties of Face, Legs, Activity, Cry and Consolability Scale for Pediatric Pain Assessment.

Purpose: We performed this systematic review to summarize the psychometric properties of Face, Legs, Activity, Cry and Consolability (FLACC) scale in pediatric patients in different settings. Methods: Two investigators independently searched PubMed, EMBASE, OVID and China National Knowledge Infrastructure (CNKI) for eligible studies through July 2021. We assessed the psychometric properties using the modified critical appraisal tool (CAT). Finally, we systematically reviewed the results of the included studies. Results: A total of 15 studies were eventually included. The overall quality of each eligible study was low to moderate. The FLACC scale has been available in different versions and in different settings. Although eligible studies have demonstrated significant clinical benefit in assessing postoperative pain in pediatric patients aged 0 to 10 years from post-anesthetic care unit (PACU), pediatric intensive care unit (PICU) and inpatient unit, and in assessing procedural pain in pediatric patients aged 0.5 to 7 years from emergency unit, immunization center and PICU, mostly without test-retest analysis. Conclusion: Although the absence of a gold standard of pain assessment, the currently available data support the usefulness of the FLACC from the perspective of criterion validity. Therefore, the FLACC scale can be considered for measuring observational pain in infants and children. However, further studies are still needed to provide more robust evidence.

Global research trends of nanotechnology for pain management.

Background: Nanotechnology has been increasingly used in healthcare during recent years. However, the systematic evaluation of research on nanotechnology for pain management is lacking. In this study, we employed a bibliometric approach to examine the status of the research and global trends of nanotechnology in relation to pain management. Methods: We selected relevant papers published in the Web of Science Core Collection database between 2013 and 2022 using search terms related to nanotechnology and pain management. Subsequently, the following bibliographic information was collected: publication year, originating country/region, affiliated authors and institutions, published journal, references cited, citation frequency, and keywords. The bibliometric software programs VOSViewer and CiteSpace were employed to obtain bibliometric statistics and perform visual analysis. Results: A total of 2680 papers were retrieved. The number of publications in the field of nanotechnology for pain management has been increasing annually since 2013. China had the highest number of published papers, whereas the United States led in total citations. The Chinese Academy of Sciences was the most prolific institution, while the Tehran University of Medical Sciences had the highest overall citations. Furthermore, De Paula was the most prolific author. Papers associated with nanotechnology for pain management were mainly published in the International Journal of Pharmaceutics, Pharmaceutics, and the International Journal of Nanomedicine. Keyword analysis showed that "in-vitro" and "drug-delivery" appeared most frequently, with the top 10 common keywords comprising nanoparticles, pain, in-vitro, drug-delivery, delivery, release, inflammation, neuropathic pain, formulation, and expression. Lastly, the latest emerging keyword was "electrochemical sensor". Conclusion: Research on applying nanotechnology for pain management is growing steadily. China is the top country in terms of number of publications, with institutions under the Chinese Academy of Sciences making significant contributions to this field. "In-vitro" and "drug-delivery" are the current hotspots in this area, with "electrochemical sensor" as the latest topic at the research forefront. However, national and inter-institutional collaborations should be strengthened to enable patients with pain disorders to benefit from nanotechnology implementation in pain management.

Application of wireless ultrasound for guided caudal anesthesia in children undergoing concealed penis surgery.

Caudal anesthesia alleviates the strong pain endured by children during surgical treatment for concealed penis. In the traditional method, anesthesiologists identify the puncture point using the 'blind probe' method, which leads to anesthesia induction failure in children. Ultrasound has recently gained wide attention for its guidance in peripheral nerve block analgesia. However, the clinical significance of wireless ultrasound - guided caudal anesthesia technology in children remains unexplored. This study investigated the clinical value of wireless ultrasound - guided caudal anesthesia in children undergoing concealed penis surgery. From April 2022 to August 2022, 120 pediatric patients aged 3-10 years were selected for concealed penis surgery. They were divided into the wireless ultrasound - guided sacral block group (group A) and the traditional sacral block group (group B), with 60 children in each group. Children in group A and group B underwent wireless ultrasound - guided caudal anesthesia and traditional caudal anesthesia, respectively. The success rates of the first puncture and total punctures, time taken for the punctures, and number of punctures were compared between the groups. The success rates of the first puncture (95% vs 68.3%) and total puncture (100% vs 90%) were significantly higher in group A than in group B (P<0.05). The average puncture time and the average number of punctures were, respectively, significantly shorter and lesser in group A than in group B (both P<0.05). Compared with the traditional method, wireless ultrasound visualization technology can effectively improve the success rate of sacral block puncture and reduce puncture time, which is worthy of clinical application.

The optimal induction dose of ciprofol combined with low-dose rocuronium in children undergoing daytime adenotonsillectomy.

Adenotonsillectomy is the most common daytime surgery performed on children. Anesthesiologists must select the optimal combination of drugs to ensure effective anesthesia effect and prompt recovery in children. The optimal induction dose of ciprofol in children is unclear. In this study, we aim to investigate the effect of different doses of ciprofol on anesthesia induction in children undergoing daytime adenotonsillectomy and provide a reference for clinical use. 144 children aged 3-12 years, ASA I-II, undergoing daytime adenotonsillectomy, were included in this clinical trial. The children were randomly divided into three groups and given 0.4 mg/kg (C4), 0.6 mg/kg (C6), or 0.8 mg/kg (C8) of ciprofol for anesthesia induction. The primary outcome was intubation conditions. Vital signs and injection pain were also recorded. The rates of unacceptable intubation conditions were 30.6%, 8.7%, and 8.2% in the C4, C6, and C8 groups (P value < 0.0167). The overall incidence of reported injection pain was 3.5%. The heart rate and mean arterial pressure did not differ between the groups at the same time points. We found that combining 0.6 mg/kg of ciprofol with low-dose rocuronium could provide optimal intubation conditions in pediatric daytime adenotonsillectomy patients. This combination resulted in stable circulation and BIS values. This study is registered at the Chinese Clinical Trial Registry (Registration number: ChiCTR2200063144, Date of Registration: 31/08/2022).

Activation of the Akt Attenuates Ropivacaine-Induced Myelination Impairment in Spinal Cord and Sensory Dysfunction in Neonatal Rats.

Prolonged exposure to local anesthetics (LAs) or intrathecal administration of high doses of LAs can cause spinal cord damage. Intraspinal administration of LAs is increasingly being used in children and neonates. Therefore, it is important to study LA-related spinal cord damage and the underlying mechanism in developmental models. First, neonatal Sprague-Dawley rats received three intrathecal injections of 0.5% ropivacaine, 1% ropivacaine, 2% ropivacaine or saline (90-min interval) on postnatal day 7. Electron microscopy, luxol fast blue staining and behavioral tests were performed to evaluate the spinal neurotoxicity caused by ropivacaine at different concentrations. Western blot analysis and immunostaining was performed to detect the expression changes of p-Akt, Akt, myelin gene regulatory factor (MYRF) and myelin basic protein (MBP) in the spinal cord treated with different concentrations of ropivacaine. Our results showed that 1% or 2% ropivacaine impaired myelination in the spinal cord and induced sensory dysfunction, but 0.5% ropivacaine did not. Moreover, 1% or 2% ropivacaine decreased the expression of p-Akt, MYRF and MBP in the spinal cord. Then, in order to further explore the role of these proteins in this model, the Akt-specific activator (SC79) was intraperitoneally injected 30 min before 2% ropivacaine treatment. Interestingly, SC79-mediated activation of Akt partly rescued ropivacaine-induced myelination impairments and sensory dysfunction. Overall, the results showed that ropivacaine caused spinal neurotoxicity in a dose-dependent manner in neonatal rats and that activation of the Akt partly rescued ropivacaine-induced these changes. These data provide insight into the neurotoxicity to the developing spinal cord caused by LAs.

Evaluation of the effect of perioperative administration of S(+)-ketamine hydrochloride injection for postoperative acute pain in children: study protocol for a prospective, multicenter, randomized, open-label, parallel-group, pragmatic clinical trial.

BACKGROUND: Inadequate postoperative pain management increases the risk of adverse events after the surgery and aggressive perioperative pain prevention has both short-term and long-term benefits. S(+)-ketamine is an N-methyl-D-aspartic acid (NMDA) receptor antagonist with a strong analgesic effect and can significantly relieve postoperative acute pain and reduce opioid consumption. However, for children, it still needs to be confirmed by large sample clinical studies. METHODS: This is a pragmatic, randomized controlled trial which will evaluate the effect of perioperative administration of S(+)-ketamine hydrochloride injection for postoperative acute pain in children in a pragmatic clinical setting. A total of 3000 children (≤17 years old) undergoing surgery will be included in this protocol. Subjects will be randomized 2:1 to either receive S(+)-ketamine hydrochloride injection or conventional therapy without S(+)-ketamine during the entire perioperative period. The primary endpoints are the area under the receiver operating characteristic (ROC) curve of Face Legs Activity Cry and Consolability (FLACC, 0-7 years old) scale score or Numerical Rating Scale (NRS, 8-17 years old) score within 48 h after surgery, and the consumption of opioids within 48 h after surgery. The secondary endpoints include the time of first use of rescue analgesics after surgery, rescue analgesia rate within 48 h after surgery, anesthesia recovery time, incidence of emergency delirium (for 0-7 years old), changes of anxiety and depression scale scores at 48 h after surgery (for 8-17 years old), incidence of intraoperative adverse events (AEs), and incidence of postoperative AEs and pharmacoeconomic indicators. AEs and serious AEs were recorded to evaluate safety. DISCUSSION: This trial will be the first pragmatic clinical trial to prospectively assess the effect of perioperative administration of S(+)-ketamine hydrochloride injection for postoperative acute pain in children, which is of great significance to the continuous optimization of clinical anesthesia and analgesia programs for children. TRIAL REGISTRATION: This trial was registered in the U.S. National Institutes of Health ClinicalTrials.gov database ( http://clinicaltrials.gov ; Registration number: NCT04834427). Registered on 8 April 2021.

Transversus Abdominis Plane Block With Liposomal Bupivacaine vs. Regular Anesthetics for Pain Control After Surgery: A Systematic Review and Meta-Analysis.

Background: Transverse abdominal plane (TAP) blocks are used to provide pain relief after abdominopelvic surgeries. The role of liposomal bupivacaine (LB) for TAP blocks is unclear. Therefore, this study aimed to synthesize evidence on the efficacy of LB vs. regular anesthetics in improving outcomes of TAP block. Methods: PubMed, Science Direct, Embase, Springer, and CENTRAL databases were searched up to July 24, 2020. Studies comparing LB with any regular anesthetic for TAP block for any surgical procedure and reporting total analgesic consumption (TAC) or pain scores were included. Results: Seven studies including five randomized controlled trials (RCTs) were reviewed. LB was compared with regular bupivacaine (RB) in all studies. A descriptive analysis was conducted for TAC due to heterogeneity in data presentation. There were variations in the outcomes of studies reporting TAC. Meta-analysis of pain scores indicated statistically significant reduction of pain with the use of LB at 12 h (MD: -0.89 95% CI: -1.44, -0.34 I2 = 0% p = 0.01), 24 h (MD: -0.64 95% CI: -1.21, -0.06 I2 = 0% p = 0.03), 48 h (MD: -0.40 95% CI: -0.77, 0.04 I2 = 0% p = 0.03) but not at 72 h (MD: -0.37 95% CI: -1.31, 0.56 I2 = 57% p = 0.43). Pooled analysis indicated no difference in the duration of hospital stay between LB and RB (MD: -0.18 95% CI: -0.49, 0.14 I2 = 61% p = 0.27). LB significantly reduced the number of days to first ambulation postsurgery (MD: -0.28 95% CI: -0.50, -0.06 I2 = 0% p = 0.01). Conclusions: Current evidence on the role of LB for providing prolonged analgesia with TAP blocks is unclear. Conflicting results have been reported for TAC. LB may result in a small reduction in pain scores up to 48 h but not at 72 h. Further, high-quality homogenous RCTs are needed to establish high-quality evidence.

Inhibiting RIPK1 Limits Neuroinflammation and Alleviates Postoperative Cognitive Impairments in D-Galactose-Induced Aged Mice.

Neuroinflammation plays a critical role in the pathogenesis of postoperative cognitive dysfunction (POCD) of the elderly patients. Receptor-interacting protein kinase1 (RIPK1) is a key molecular switch modulating inflammation, apoptosis and necroptosis. Here, we investigated whether inhibiting RIPK1 by necrostatin-1 (Nec-1) could limit neuroinflammation and attenuate POCD in D-Galactose (D-Gal)-induced aged mice. The mice were subjected to anesthesia and partial hepatectomy, and necrostatin-1 was administered intraperitoneally 1 h prior to anesthesia and surgery. Cognitive function and movement were tested 24 h after surgery by open field, Barnes maze and puzzle box. The hippocampal tissues were collected to detect the following: neuroinflammation (Iba-1, IL-1α, IL-1ß, TNF-α), Necroptosis (Propidium Iodide (PI) labeling, RIPK1, nuclear transcription factor kappa B (NF-κB) and neuroplasticity (doublecortin (DCX), NR2B, GluA1, GluA2). We found that anesthesia and surgery induced a significant deficit in spatial memory acquisition and impairment of executive function and memory to simple task in D-Galactose-induced aged mice. Inhibiting RIPK1 by necrostatin-1 strikingly mitigated cognitive impairment and alleviated postoperative amplified neuroinflammation, necroptosis and GluA1 loss in hippocampus. These suggest that targeting RIPK1 by necrostatin-1 may serve as a promising therapeutics for prevention of POCD in elderly patients.