EIF2AK2 protein targeted activation of AIM2-mediated PANoptosis promotes sepsis-induced acute kidney injury.

BACKGROUND: Acute kidney injury (AKI) frequently occurs as a complication of sepsis. PANoptosis refers to a type of inflammatory programmed cell death that exhibits key characteristics of apoptosis, necroptosis, and pyroptosis. Here, we evaluated the role of absent in melanoma 2 (AIM2) and eukaryotic translation initiation factor 2 alpha kinase 2 (EIF2AK2) in septic AKI. METHODS: A septic AKI model was created through cecal ligation and puncture (CLP), while an in vitro model was developed using lipopolysaccharide (LPS)-stimulated HK2 cells. Hematoxylin and eosin (HE), Periodic acid-Schiff (PAS), and TUNEL staining were conducted to assess kidney injury in mice. Levels of serum creatinine (Scr) and blood urea nitrogen (BUN) were detected by kits. Gene expression was detected utilizing RT-qPCR, and Western blot was used to test protein levels. Immunofluorescence was employed to measure EIF2AK2 and AIM2 expression in mouse kidney tissue. Lactate dehydrogenase (LDH) activity assay was conducted to evaluate cytotoxicity. Co-immunoprecipitation (Co-IP) was performed to verify the binding relationship between EIF2AK2 and AIM2. RESULTS: AIM2 expression was increased in the renal tissue of mice subjected to CLP. Activation of the inflammasome and PANoptosis were observed in the renal tissue of CLP mice. AIM2 depletion attenuated PANoptosis in LPS-treated HK-2 cells. Additionally, EIF2AK2 could directly target AIM2, leading to a positive regulation of AIM2 expression. Notably, EIF2AK2 induced PANoptosis through upregulating AIM2 in HK-2 cells stimulated by LPS. CONCLUSIONS: Our results revealed the important role of EIF2AK2-induced AIM2 upregulation in the activation of PANoptosis during septic AKI.

Renal tissue from CLP mice exhibited an increase in AIM2 expression.Renal tissue from CLP mice demonstrated inflammasome activation and PANoptosis.AIM2 silencing reduced PANoptosis in LPS-treated HK-2 cells.EIF2AK2 directly targeted AIM2 and positively regulated its expression.EIF2AK2 promoted PANoptosis via AIM2 in LPS-triggered HK-2 cells.

Treatment Options for Signet Ring Cell Carcinoma of the Urinary Bladder: A Population-Based Study.

OBJECTIVES: Signet ring cell carcinoma (SRCC) of the urinary bladder is a rare and highly aggressive form of bladder cancer, with no widely agreed-upon treatment strategy. The aim of this study was to identify important factors influencing patient prognosis and to assess how various treatment approaches affect survival outcomes. METHODS: A retrospective study was conducted using data from the Surveillance, Epidemiology, and End Results (SEER) Program, including patients with bladder primary SRCC who were presented between 2000 and 2017. Univariate and multivariate Cox regression models were used to examine the impact of various factors on cancer-specific survival (CSS) and overall survival (OS). Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were applied to homogenize both groups. The impact of different treatment regimens on patient CSS and OS was analyzed using the Kaplan-Meier method. RESULTS: A total of 33 cases of non-muscular invasive SRCC and 210 cases of muscular invasive SRCC were included in this study. Multivariate analysis identified race, TNM stage, and surgical method as independent variables influencing both OS and CSS. In non-muscle invasive bladder SRCC patients, radical cystectomy showed no CSS benefit compared to transurethral resection of bladder tumors (P = 0.304). For muscle invasive SRCC, patients who underwent partial cystectomy had better OS and CSS compared to those who underwent radical cystectomy (P = 0.019, P = 0.024). However, after conducting a PSM analysis, the differences between the two surgical outcomes were not statistically significant (P = 0.504, P = 0.335). Lymphadenectomy, chemotherapy, and radiation did not show any benefit to the prognosis of patients. CONCLUSION: This study identified race, TNM stage, and surgical approach as significant independent predictors for SRCC outcomes. Simple radical cystectomy and partial cystectomy proved to be effective treatments for SRCC. The optimal treatment option still needs to be supported by a number of prospective research trials.

Dexmedetomidine alleviates acute postoperative anxiety in rats by suppressing the NF-ĸB pathway.

Evidence suggests that surgical procedures can effect the central nervous system and lead to changes in mood and behavior, rarely understood about the role of acute inflammation in promoting acute anxiety postoperatively. This study was designed to explore the possible mechanism of dexmedetomidine (DEX, a2-adrenergic receptor agonist) for reducing acute postoperative anxiety, which may be related to the activation of nuclear factor kappa B (NF-κB) and downstream signal pathway in the hippocampus. Experiments were conducted with rat, the elevated plus-maze and open field test were performed to evaluate anxiety-like behavior. Inhibit DEX with Atipamezole (AT, α2-adrenergic receptor antagonist) and inhibit NF-κB with Pyrrolidinedithiocarbamate (PDTC, inhibit phosphorylation of IκB, prevent the activation of NF-κB), the level of interleukin-6 (IL-6), IL-1ß, IL-10 and Tumor necrosis factor-α (TNF-α); the nuclear translocation of NF-κB in the hippocampus and anxiety-like behavior were measured. Rats exhibited anxiety-like behavior at 6h and 12h after surgery. Preoperative administration of DEX significantly alleviated postoperative anxiety-like behavior. DEX premedication inhibited the nuclear translocation of NF-κB alleviate acute postoperative anxiety. These findings are the first to show that acute postoperative anxiety may be related to NF-κB nuclear translocation in the hippocampus in rats, which can be alleviated by DEX premedication.

Is there any difference in urinary continence between bilateral and unilateral nerve sparing during radical prostatectomy? A systematic review and meta-analysis.

CONTEXT: In men with prostate cancer, urinary incontinence is one of the most common long-term side effects of radical prostatectomy (RP). The recovery of urinary continence in patients is positively influenced by preserving the integrity of the neurovascular bundles (NVBs). However, it is still unclear if bilateral nerve sparing (BNS) is superior to unilateral nerve sparing (UNS) in terms of post-RP urinary continence. The aim of this study is to systematically compare the differences in post-RP urinary continence outcomes between BNS and UNS. METHODS: The electronic databases of PubMed and Web of Science were comprehensively searched. The search period was up to May 31, 2023. English language articles comparing urinary continence outcomes of patients undergoing BNS and UNS radical prostatectomy were included. Meta-analyses were performed to calculate pooled relative risk (RR) estimates with 95% confidence intervals for urinary continence in BNS and UNS groups at selected follow-up intervals using a random-effects model. Sensitivity analyses were performed in prospective studies and robotic-assisted RP studies. RESULTS: A meta-analysis was conducted using data from 26,961 participants in fifty-seven studies. A meta-analysis demonstrated that BNS improved the urinary continence rate compared to UNS at all selected follow-up points. RRs were 1.36 (1.14-1.63; p = 0.0007) at ≤ 1.5 months (mo), 1.28 (1.08-1.51; p = 0.005) at 3-4 mo, 1.12 (1.03-1.22; p = 0.01) at 6 mo, 1.08 (1.05-1.12; p < 0.00001) at 12 mo, and 1.07 (1.00-1.13; p = 0.03) at ≥ 24 mo, respectively. With the extension of the follow-up time, RRs decreased from 1.36 to 1.07, showing a gradual downward trend. Pooled estimates were largely heterogeneous. Similar findings were obtained through sensitivity analyses of prospective studies and robotic-assisted RP studies. CONCLUSION: The findings of this meta-analysis demonstrate that BNS yields superior outcomes in terms of urinary continence compared to UNS, with these advantages being sustained for a minimum duration of 24 months. It may be due to the real effect of saving the nerves involved. Future high-quality studies are needed to confirm these findings.

Enzyme-Responsive Modular Peptides Enhance Tumor Penetration of Quantum Dots via Charge Reversal Strategy.

Quantum dots (QDs) are colloidal semiconductor nanoparticles acting as fluorescent probes for detection, disease diagnosis, and photothermal and photodynamic therapy. However, their performance in cancer treatment is limited by inadequate tumor accumulation and penetration due to the larger size of nanoparticles compared to small molecules. To address this challenge, charge reversal nanoparticles offer an effective strategy to prolong blood circulation time and achieve enhanced endocytosis and tumor penetration. In this study, we leveraged the overexpressed γ-glutamyl transpeptidase (GGT) in many human tumors and developed a library of modular peptides to serve as water-soluble surface ligands of QDs. We successfully transferred the QDs from the organic phase to the aqueous phase within 5 min. And through systematic tuning of the peptide sequence, we optimized the fluorescent stability of QDs and their charge reversal behavior in response to GGT. The resulting optimal peptide stabilized QDs in aqueous solution with a high fluorescent retention rate of 93% after three months and realized the surface charge reversal of QDs triggered by GGT in vitro. The binding between the peptide and QD surface was investigated by using saturation transfer differential nuclear magnetic resonance (STD NMR). Thanks to its charge reversal ability, the GGT-responsive QDs exhibited enhanced cellular uptake in GGT-expressing cancer cells and deeper penetration in the 3D multicellular spheroids. This enzyme-responsive modular peptide can lead to specific tumor targeting and deeper tumor penetration, holding great promise to enhance the treatment efficacy of QD-based theranostics.

Demographic characteristics and prognosis of HHV8-positive diffuse large B-cell lymphoma, not otherwise specified: Insights from a population-based study with a 10-year follow-up.

HHV8-positive diffuse large B-cell lymphoma, not otherwise specified (HDN) is a subtype of lymphoma that usually arises in association with HHV8-positive multicentric Castleman disease. However, the epidemiology, treatment patterns, and survival outcomes of HDN are poorly understood. A retrospective analysis was performed for 67 patients with HDN diagnosed from 2011 to 2020 using the SEER database. The demographic characteristics, treatment modalities, and survival outcomes of HDN patients were evaluated. Kaplan-Meier analysis and Cox regression analysis were employed to identify prognostic factors for overall survival (OS) and disease-specific survival (DSS). The age-adjusted incidence rate of HDN was 0.010 per 100,000 person-years. The median age at diagnosis was 51.8 years with male predominance. The primary site distribution was mainly nodal (79.1%), while the extranodal sites were rarely involved (20.9%). The majority of patients were white (65.7%). Only 3.0% of patients received radiotherapy, while 55.2% received chemotherapy. The 1-year, 3-year, and 5-year OS was 67.4%, 65.6%, 58.4%, and 56.3%, respectively, and the corresponding DSS was 73.1%, 73.1%, and 67.8%, respectively. The diagnosis year group of 2016-2020 had a significantly worse OS than the diagnosis year group of 2011-2015 (P = .040), but not for DSS (P = .074). No significant survival improvement was observed in patients underwent chemotherapy. Age and marital status were independent prognostic factors for OS, and age was an independent prognostic factor for DSS. In conclusion, HDN is a rare and aggressive disease, our study provides a comprehensive overview of the epidemiology, treatment patterns and survival outcomes of HDN patients for the first time. We revealed that older age and marital status of single were associated with worse survival of HDN, while chemotherapy was not associated with improved survival outcomes in HDN patients.

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).

Effect of epidural block on surgical conditions during pediatric subumbilical laparoscopic surgery involving a supraglottic airway: a randomized clinical trial.

Background: Few studies have examined the effect of epidural block on surgical conditions during pediatric subumbilical laparoscopic surgery involving a supraglottic airway (SGA). This study investigated the surgical condition scores for such procedures in cases where neuromuscular block, epidural block, or neither was used. Methods: A total of 150 patients aged 3-12 years undergoing laparoscopic orchiopexy with a ProSeal SGA device were randomly allocated to one of three groups: the control group (did not receive neuromuscular block and epidural block), the NMB group [received a neuromuscular block (train-of-four 1-2 twitches) using rocuronium], or the EDB group (received an epidural block using ropivacaine). The primary outcome was the quality of surgical conditions evaluated with the Leiden-Surgical Rating Scale by the blinded surgeon. The secondary outcome measures included intraoperative hemodynamic data (including mean arterial pressure and heart rate), the SGA device removal time, the PACU discharge time, the pain score in the PACU and intraoperative adverse events (including bradycardia, hypotension, peak airway pressure > 20 cmH2O, and poor or extremely poor surgical conditions occurred during the operation). Statistical analysis was performed with one-way analysis of variance, the Kruskal-Wallis test, the chi-square test or Fisher's exact test. Bonferroni corrections for multiple comparisons were made for primary and secondary outcomes. Results: Surgical condition scores were significantly higher in the NMB and EDB groups than in the control group (median difference: 0.8; 95% confidence interval [CI], 0.5-1.0; p < 0.0001; and median difference: 0.7; 95% CI, 0.5-0.8; p < 0.0001, respectively). Blood pressure and heart rate were significantly lower in the EDB group than in the other two groups (p < 0.0001 and p = 0.004). Patients in the EDB group had significantly lower pain scores during PACU than those in the other two groups (p < 0.0001). The sufentanil dose was lower in the EDB group than in the other two groups (p = 0.001). Conclusion: Epidural block can improve surgical conditions during pediatric subumbilical laparoscopic surgery involving a SGA to a degree comparable to that with moderate neuromuscular block.

Multi-Stimuli-Responsive Nanoparticles Formed of POSS-PEG for the Delivery of Boronic Acid-Containing Therapeutics.

Polymeric vehicles often exhibit batch-to-batch variations due to polydispersity, limiting their reproducibility for biomedical applications. In contrast, polyhedral oligomeric silsesquioxane (POSS) has emerged as an attractive candidate for drug delivery due to its precise chemical structure and rigid molecular shape. A promising strategy to enhance drug efficacy while reducing systemic toxicity is the development of multi-stimuli-responsive delivery systems capable of targeted drug release at a disease site. Herein, we developed a drug delivery platform based on POSS-polymer conjugates. By functionalizing the POSS with amino groups and establishing B-N coordination with boronic acids, the nanoparticles (NPs) exhibit responsive behavior to stimuli, including adenosine-5'-triphosphate (ATP), acidic pH, and nucleophilic reagents. We successfully encapsulated two boronic acid-containing molecules: tetraphenylethylene (TPE), serving as a fluorescent probe, and bortezomib (BTZ), an anticancer drug. The TPE@NPs were employed to visualize the cellular uptake of NPs by tumor cells, while the BTZ@NPs exhibited increased cytotoxicity in tumor cells compared with normal cells. This POSS-PEG conjugate offers a nanoparticle platform for encapsulating versatile boronic acid-containing molecules, thereby enhancing drug efficacy while minimizing systemic toxicity. Given the wide-ranging applications of boronic acid-containing molecules in biomedicine, our platform holds significant promise for the development of intelligent drug delivery systems for diagnostics and therapeutics.

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).

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.

Uridine alleviates high-carbohydrate diet-induced metabolic syndromes by activating sirt1/AMPK signaling pathway and promoting glycogen synthesis in Nile tilapia (Oreochromis niloticus).

Carbohydrates have a protein sparing effect, but long-term feeding of a high-carbohydrate diet (HCD) leads to metabolic disorders due to the limited utilization efficiency of carbohydrates in fish. How to mitigate the negative effects induced by HCD is crucial for the rapid development of aquaculture. Uridine is a pyrimidine nucleoside that plays a vital role in regulating lipid and glucose metabolism, but whether uridine can alleviate metabolic syndromes induced by HCD remains unknown. In this study, a total of 480 Nile tilapia (Oreochromis niloticus) (average initial weight 5.02 ± 0.03 g) were fed with 4 diets, including a control diet (CON), HCD, HCD + 500 mg/kg uridine (HCUL) and HCD + 5,000 mg/kg uridine (HCUH), for 8 weeks. The results showed that addition of uridine decreased hepatic lipid, serum glucose, triglyceride and cholesterol (P < 0.05). Further analysis indicated that higher concentration of uridine activated the sirtuin1 (sirt1)/adenosine 5-monophosphate-activated protein kinase (AMPK) signaling pathway to increase lipid catabolism and glycolysis while decreasing lipogenesis (P < 0.05). Besides, uridine increased the activity of glycogen synthesis-related enzymes (P < 0.05). This study suggested that uridine could alleviate HCD-induced metabolic syndrome by activating the sirt1/AMPK signaling pathway and promoting glycogen synthesis. This finding reveals the function of uridine in fish metabolism and facilitates the development of new additives in aquatic feeds.

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.

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 preoperative pulmonary artery pressure on the prognosis of end-stage heart failure patients after heart transplantation.

OBJECTIVE: To evaluate the effect of preoperative pulmonary artery pressure on perioperative outcome of end-stage heart failure patients undergoing heart transplantation. METHODS: Retrospective analysis was undertaken on the clinical data of patients receiving heart transplantation in the Department of Cardiovascular Surgery of our hospital from March 2017 to March 2022. A ROC curve analysis was developed between mean pulmonary artery pressure (mPAP) and postoperative mortality using mPAP as diagnostic criteria. Patients were divided into groups based on this threshold to determine the best mPAP threshold value for predicting postoperative nosocomial mortality, and the differences in preoperative and intraoperative data, postoperative complications, and clinical prognosis of patients in the two groups were compared. Patients were followed up to draw the survival curve of patients in the two groups. RESULTS: The study enlisted the participation of 105 patients. ROC curve research revealed that preoperative pulmonary artery pressure was substantially linked with death following heart transplantation, with mPAP = 30.5mmHg being the best threshold. The group with mPAP ≥ 30.5mmHg had a greater incidence of postoperative ECMO support (28.2% vs. 10.6%, P = 0.021) and a higher incidence of in-hospital mortality (15.4% vs. 1.5%, P = 0.019) than the group with mPAP < 30.5mmHg. The postoperative survival rates of 105 patients were 91.3%, 88.7%, 81.6%, and 77.5% at 1, 2, 3, and 4 years, respectively, however, there was no significant difference between the two groups of patients in the postoperative intermediate-far survival rate (P = 0.431). CONCLUSIONS: Preoperative pulmonary artery pressure in patients with end-stage heart failure is intimately correlated with perioperative prognosis of heart transplant recipients. The optimal cut-off mPAP value in predicting perioperative prognosis of heart transplant recipients is 30.5mmHg. In the high mPAP group, perioperative ECMO support rate and perioperative mortality rate are high, which do not affect the medium and long-term prognosis of the recipients undergoing heart transplantation.

Gelatin-based anticancer drug delivery nanosystems: A mini review.

Drug delivery nanosystems (DDnS) is widely developed recently. Gelatin is a high-potential biomaterial originated from natural resources for anticancer DDnS, which can effectively improve the utilization of anticancer drugs and reduce side effects. The hydrophilic, amphoteric behavior and sol-gel transition of gelatin can be used to fulfill various requirements of anticancer DDnS. Additionally, the high number of multifunctional groups on the surface of gelatin provides the possibility of crosslinking and further modifications. In this review, we focus on the properties of gelatin and briefly elaborate the correlation between the properties and anticancer DDnS. Furthermore, we discuss the applications of gelatin-based DDnS in various cancer treatments. Overall, we have summarized the excellent properties of gelatin and correlated with DDnS to provide a manual for the design of gelatin-based materials for DDnS.

Effectiveness of prophylactic antimicrobial levofloxacin against postureteroscopic lithotripsy infection: A multicenter prospective open-label randomized controlled trial.

BACKGROUND: To verify the appropriate prophylactic agent to prevent ureteroscopic lithotripsy infection, which is safe, effective, convenient, reasonable, and with best pharmacoeconomic benefit ratio, to provide evidence for clinical practice. METHODS: This study is a multicenter, open-label, randomized, positive drug-controlled trial design. From January 2019 to December 2021, patients with ureteral calculi who were going to undergo retrograde flexible ureteroscopic lithotripsy were selected from urology departments in 5 research centers. The patients enrolled were randomly divided into the experimental group and the control group according to the random number table by blocking randomization. In the experimental group (Group A), 0.5 g levofloxacin was given 2 to 4 hours before surgery. In the control group (Group B), cephalosporin was injected 30 minutes before surgery. The infectious complications, the incidence of adverse drug reactions and the economic benefit ratio were compared between the 2 groups. RESULTS: A total of 234 cases were enrolled. There was no statistically significant difference between the 2 groups at baseline. Postoperative infection complications were 1.8% in the experimental group, which was significantly lower than 11.2% in control group. The type of infection complication in both groups was asymptomatic bacteriuria. The cost of drugs in the experimental group was 19.89 ± 13.11 yuan, which was significantly lower than cost of drugs in the control group of 41.75 ± 30.12 yuan. The levofloxacin application had favorable cost-effectiveness ratio. The difference in safety between 2 groups was not significant. CONCLUSION: The application of levofloxacin is safe, effective, and low-cost regimen for postureteroscopic lithotripsy infection prevention.

X-Ray-triggered Carbon Monoxide and Manganese Dioxide Generation based on Scintillating Nanoparticles for Cascade Cancer Radiosensitization.

Carbon monoxide (CO) is an endogenous signaling molecule with broad therapeutic effects. Here, a multifunctional X-ray-triggered carbon monoxide (CO) and manganese dioxide (MnO2 ) generation nanoplatform based on metal carbonyl and scintillating nanoparticles (SCNPs) is reported. Attributed to the radioluminescent characteristic of SCNPs, UV-responsive Mn2 (CO)10 is not only indirectly activated to release CO by X-ray but can also be degraded into MnO2 . A high dose of CO can be used as a glycolytic inhibitor for tumor suppression; it will also sensitize tumor cells to radiotherapy. Meanwhile MnO2 , as the photolytic byproduct of Mn2 (CO)10 , has both glutathione (GSH) depletion and Fenton-like Mn2+ delivery properties to produce highly toxic hydroxyl radical (⋅OH) in tumors. Thus, this strategy can realize X-ray-activated CO release, GSH depletion, and ⋅OH generation for cascade cancer radiosensitization. Furthermore, X-ray-activated Mn2+ in vivo demonstrates an MRI contrast effect, making it a potential theranostic nanoplatform.