Objective  To evaluate the effect of intraoperative multimodal analgesia on the early postoperative quality of recovery in end-stage head and neck cancer patients undergoing open gastrostomy surgery.  Methods  This was a prospective, parallel, randomized controlled study. The research subjects were end-stage head and neck cancer patients who underwent elective open gastrostomy at Beijing Tongren Hospital affiliated to Capital Medical University from November 2022 to May 2023. The patients were randomly divided into local anesthesia group and multimodal analgesia group at a 1∶1 ratio. For local anesthesia group, 0.25% ropivacaine 20-30 mL was administered for local infiltration anesthesia. For multimodal analgesia group, the anesthesia method was nerve block + intravenous analgesia: ultrasound-guided left transverse abdominis plane block (0.25% ropivacaine 0.3 mL/kg)+bilateral rectus abdominis sheath block (0.25% ropivacaine 0.3 mL/kg per side)+intravenous injection of oxycodone 0.1 mg/kg, flurbiprofen 1 mg/kg, and dexamethasone 0.2 mg/kg. The primary outcome measure was the quality of requirements-15 (QoR-15) score at postoperative 24 h, while the secondary outcome measures were the QoR-15 score at postoperative 48 h, the numerical rating scale (NRS) and Bruggemann comfort scale (BCS) scores at different time points after the surgery, the first time of rescue analgesia, the first time of off-bed activity and intestinal exhaust, as well as the incidences of adverse reactions within postoperative 48 h.  Results  A total of 46 patients with end-stage head and neck cancer who underwent open gastrostomy and met the inclusion and exclusion criteria were ultimately enrolled, with 23 patients in multimodal analgesia group and 23 patients in local anesthesia group. There was no statistically significant difference in preoperative QoR-15 scores between the two groups (P > 0.05). Multimodal analgesia group had higher QoR-15 scores at 24 h postoperatively[(81.77±8.91) vs. (71.46±7.61), P < 0.05] and 48 h postoperatively[(86.26±7.92) vs. (80.13±6.98), P < 0.05], and the difference in QoR-15 scores at 24 h postoperatively was clinically significant. Compared with local anesthesia group, at 6 h and 24 h after surgery, the multimodal analgesia group showed a decrease in NRS scores at rest and during exercise, while the comfort BCS score increased (all P < 0.05). Multimodal analgesia group also had a delayed time for the first rescue analgesia, a reduced incidence of rescue analgesia within 48 h after surgery, an earlier time for first postoperative off-bed activity and intestinal exhaust (all P < 0.05). The incidence of adverse reactions in multimodal analgesia group and local anesthesia group was 8.70% and 13.04%, respectively, but the difference was not statistically significant (P > 0.05).  Conclusion  Intraoperative multimodal analgesia can effectively alleviate postoperative pain, increase the comfortable degree, shorten the first time of postoperative off-bed activity and intestinal exhaust, and accordingly improve the quality of early postoperative recovery in patients undergoing open gastrostomy.

Objective To evaluate the effect of remimazolam combined with desflurane and flumazenil antagonism for anesthesia during ophthalmic day surgery.Methods This is a prospective randomized controlled trial.A total of 64 patients undergoing elective general anesthesia with laryngeal mask during ophthalmic day surgery were selected and randomly assigned to propofol group(n = 32)and remimazolam group(n = 32).The propofol group was given propofol anesthesia induction and propofol combined with diflurane anesthesia maintenance;the remazolam group was given remazolam anesthesia induction and remazolam combined with diflurane anesthesia maintenance,and flumazenil antagonism was given intravenously at the end of the operation.Continuous intravenous infusion of remifentanil was administered during surgery in both groups.The primary outcome was emergence time.The secondary outcome included changes in intraoperative hemodynamic parameters,extubation time,time to leaving the operating room,duration of postoperative recovery room(PACU)stay,and the occurrence of other perioperative adverse reactions.Results Emergence time,extubation time,and time to leaving the operating room in remimazolam group were significantly shorter than those in group propofol(P<0.05)[(4.11±1.17)vs.(8.64±2.77)min,(4.61±1.11)vs.(9.90±2.81)min and(6.60±2.01)vs.(11.74±3.11)min,respectively].The incidences of intraopera-tive hypotension and bradycardia in the remimazolam group were significantly lower than that in the propofol group(P<0.05);There was no statistically difference in the duration of PACU stay and the incidence of postoperative complications between the two groups(P>0.05).Conclusion Remimazolam combined with desflurane general anesthesia and flumazenil antagonism for anesthesia management in ophthalmic day surgery could significantly shorten the time of emergence and extubation,help to maintain hemodynamic stability with fewer adverse reactions,and improve the safety of ophthalmic daytime surgery,which is worthy of clinical promotion and application.

Background::Renal ischemia-reperfusion (R-I/R) injury is the most prevalent cause of acute kidney injury, with high mortality and poor prognosis. However, the underlying pathological mechanisms are not yet fully understood. Therefore, this study aimed to investigate the role of N-myc downstream-regulated gene 2 ( Ndrg2) in R-I/R injury. Methods::We examined the expression of Ndrg2 in the kidney under normal physiological conditions and after R-I/R injury by immunofluorescence staining, real-time polymerase chain reaction, and western blotting. We then detected R-I/R injury in Ndrg2-deficient ( Ndrg2-/-) mice and wild type ( Ndrg2+/+) littermates in vivo, and detected oxygen and glucose deprivation and reperfusion (OGD-R) injury in HK-2 cells. We further conducted transcriptomic sequencing to investigate the role of Ndrg2 in R-I/R injury and detected levels of oxidative stress and mitochondrial damage by dihydroethidium staining, biochemical assays, and western blot. Finally, we measured the levels of mitophagy in Ndrg2+/+ and Ndrg2-/- mice after R-I/R injury or HK-2 cells in OGD-R injury. Results::Ndrg2 was primarily expressed in renal proximal tubules and its expression was significantly decreased 24 h after R-I/R injury. Ndrg2-/- mice exhibited significantly attenuated R-I/R injury compared to Ndrg2+/+ mice. Transcriptomics profiling showed that Ndrg2 deficiency induced perturbations of multiple signaling pathways, downregulated inflammatory responses and oxidative stress, and increased autophagy following R-I/R injury. Further studies revealed that Ndrg2 deficiency reduced oxidative stress and mitochondrial damage. Notably, Ndrg2 deficiency significantly activated phosphatase and tensin homologue on chromosome ten-induced putative kinase 1 (PINK1)/Parkin-mediated mitophagy. The downregulation of NDRG2 expression significantly increased cell viability after OGD-R injury, increased the expression of heme oxygenase-1, decreased the expression of nicotinamide adenine dinucleotide phosphate oxidase 4, and increased the expression of the PINK1/Parkin pathway. Conclusion::Ndrg2 deficiency might become a therapy target for R-I/R injury by decreasing oxidative stress, maintaining mitochondrial homeostasis, and activating PINK1/Parkin-mediated mitophagy.

Objective:To evaluate the effect of gender factors on the potency of oxycodone inhibiting responses to laryngeal mask airway (LMA) insertion in patients.Methods:American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ patients, aged 18-59 yr, with a body mass index of 18-28 kg/m 2, scheduled for elective surgery with general anesthesia using LMA, were divided into 2 groups according to gender: male group (group M) and female group (group F). The dose of oxycodone was determined by using modified Dixon′s up-and-down method. Oxycodone 0.1 mg/kg was intravenously infused in the first patient of each group, and propofol 3 μg/ml was simultaneously given by target-controlled infusion. When bispectral index value ≤60 after the equilibration between effect-site concentration and plasma concentration was achieved, cisatracurium 0.2 mg/kg was intravenously injected, and 3 min later the LMA was inserted. When the response to LMA insertion was positive, the dose of oxycodone was increased in the next patient, otherwise the dose was decreased, and the ratio between the two successive doses was 1.1. The process was repeated until the 7th turning point occurred. The positive response to LMA insertion was defined as an increase in the maximum heart rate or in the maximum mean arterial pressure >20% of the baseline value with 2 min after insertion. The median effective dose (ED 50) and 95% confidence interval of oxycodone inhibiting responses to LMA insertion were calculated by the probit analysis. Results:Twenty-eight cases were finally included in M group and 25 cases in F group. The ED 50 (95% confidence interval) of oxycodone was 0.105 (0.091-0.115) mg/kg in group M and 0.087 (0.082-0.094) mg/kg in group F. The ED 50 of oxycodone was significantly higher in group M than in group F ( P<0.001). Conclusions:The effect of oxycodone inhibiting responses to nociceptive stimulation induced by LMA insertion is related to gender factors, with increased potency in females.

BACKGROUND: Posttraumatic stress disorder (PTSD) and depression are highly comorbid. Psilocybin exerts substantial therapeutic effects on depression by promoting neuroplasticity. Fear extinction is a key process in the mechanism of first-line exposure-based therapies for PTSD. We hypothesized that psilocybin would facilitate fear extinction by promoting hippocampal neuroplasticity. METHODS: First, we assessed the effects of psilocybin on percentage of freezing time in an auditory cued fear conditioning (FC) and fear extinction paradigm in mice. Psilocybin was administered 30 min before extinction training. Fear extinction testing was performed on the first day; fear extinction retrieval and fear renewal were tested on the sixth and seventh days, respectively. Furthermore, we verified the effect of psilocybin on hippocampal neuroplasticity using Golgi staining for the dendritic complexity and spine density, Western blotting for the protein levels of brain derived neurotrophic factor (BDNF) and mechanistic target of rapamycin (mTOR), and immunofluorescence staining for the numbers of doublecortin (DCX)- and bromodeoxyuridine (BrdU)-positive cells. RESULTS: A single dose of psilocybin (2.5 mg/kg, i.p.) reduced the increase in the percentage of freezing time induced by FC at 24 h, 6th day and 7th day after administration. In terms of structural neuroplasticity, psilocybin rescued the decrease in hippocampal dendritic complexity and spine density induced by FC; in terms of neuroplasticity related proteins, psilocybin rescued the decrease in the protein levels of hippocampal BDNF and mTOR induced by FC; in terms of neurogenesis, psilocybin rescued the decrease in the numbers of DCX- and BrdU-positive cells in the hippocampal dentate gyrus induced by FC. CONCLUSIONS A single dose of psilocybin facilitated rapid and sustained fear extinction; this effect might be partially mediated by the promotion of hippocampal neuroplasticity. This study indicates that psilocybin may be a useful adjunct to exposure-based therapies for PTSD and other mental disorders characterized by failure of fear extinction.
Humans ; Mice ; Animals ; Psilocybin/metabolism* ; Fear ; Extinction, Psychological ; Brain-Derived Neurotrophic Factor/metabolism* ; Bromodeoxyuridine/pharmacology* ; Hippocampus/metabolism* ; Neuronal Plasticity ; TOR Serine-Threonine Kinases/metabolism*

Humans ; Heparin/therapeutic use* ; Extracorporeal Membrane Oxygenation ; Respiratory System ; Respiratory Insufficiency

Objective:To observe the occurrence of residual neuromuscular blockade (RNMB) in post anesthesia care unit (PACU) in patients undergoing selective laryngeal surgery under general anesthesia and provide reference for improving the safety of muscle relaxants during the perioperative period.Methods:The adult patients who underwent laryngeal surgery in Beijing Tongren Hospital, Capital Medical University from July 2020 to March 2021 were collected. According to the muscle relaxants used in the surgery, the patients were divided into rocuronium bromide group, mivacurium chloride group, and cisatracurium group. The general information of patients in the different groups [age, body mass index, American Society of Anesthesiologists (ASA) classification, etc.], duration of surgery, anesthesia time, stay time in PACU, and recovery of neuromuscular function (expressed using train of four ratio, abbreviated as TOFr) were recorded and analyzed. The ability to speak and raise one′s head in PACU, as well as the occurrence of adverse events such as gastroesophageal reflux, aspiration, and dyspnea were also recorded.Results:A total of 320 patients were enrolled in the study, including 188 males (58.8%) and 132 females (41.2%), with a mean age of (50±13) years. The duration of surgery was (38.6±30.1) minutes, anesthesia time was (57.2±32.8) minutes, and stay time in PACU was (34.6±11.4) minutes. There were 115, 141, and 64 patients in the rocuronium bromide, mivacurium chloride, and cisatracurium groups, respectively. The differences in age, body mass index, and ASA grade in patients among the 3 groups were not significant (all P>0.05). The anesthesia time and duration of surgery in patients of the mivacurium chloride group were shorter than those of the rocuronium bromide and cisatracurium groups [(43.53±23.90) minutes vs. (67.54±37.72) minutes and (68.84±29.34) minutes; (26.87±22.18) minutes vs. (47.16±34.83) minutes and (48.84±27.57) minutes], and the differences were statistically significant (all P<0.01). The difference in stay time in PACU among the 3 groups was not statistically significant ( P>0.05). At the moment of entering PACU, 272 (88.6%) of 320 patients had TOFr<0.9, of which 105 (32.8%) had TOFr<0.7; when leaving PACU, the TOFr of all patients was>0.9. Except the time point of leaving PACU, TOFr in the rocuronium bromide group at the other time points were higher than those in the cisatracurium group (all P<0.01). Except the 2 time points of the moment of entering and leaving PACU, TOFr in the mivacurium chloride group was higher than those in the cisatracurium group (all P<0.01). At the moment of entering PACU and 5 minutes after entering PACU, TOFr in the mivacurium chloride group was lower than those in the rocuronium bromide group (all P<0.05). When entering PACU, 79 of 320 patients had saturation of pulse oximetry (SpO 2)<0.95 and the difference in SpO 2 among the 3 groups was statistically significant ( P=0.029), of which 4 cases (6.25%) had SpO 2<0.90 in the cisatracurium group, and the incidence of hypoxemia was higher than that in the other 2 groups. The differences in ability of speach and head lifting of patients among the 3 groups when entering PACU were statistically significant ( P=0.036, P<0.001). No adverse events such as reflux, or aspiration, dyspnea occurred in patients in PACU. Conclusions:The incidence of RNMB in patients undergoing laryngeal surgery entering PACU immediately is high and the degree of RNMB is more severe, with TOFr gradually increasing and RNMB decreasing over time. The patients who receive cisatracurium have a high incidence and severity of postoperative RNMB. Routine monitoring and neuromuscular monitoring in PACU are beneficial for patients′ perioperative safety.

Objective:To observe the occurrence of residual neuromuscular blockade (RNMB) in post anesthesia care unit (PACU) in patients undergoing selective laryngeal surgery under general anesthesia and provide reference for improving the safety of muscle relaxants during the perioperative period.Methods:The adult patients who underwent laryngeal surgery in Beijing Tongren Hospital, Capital Medical University from July 2020 to March 2021 were collected. According to the muscle relaxants used in the surgery, the patients were divided into rocuronium bromide group, mivacurium chloride group, and cisatracurium group. The general information of patients in the different groups [age, body mass index, American Society of Anesthesiologists (ASA) classification, etc.], duration of surgery, anesthesia time, stay time in PACU, and recovery of neuromuscular function (expressed using train of four ratio, abbreviated as TOFr) were recorded and analyzed. The ability to speak and raise one′s head in PACU, as well as the occurrence of adverse events such as gastroesophageal reflux, aspiration, and dyspnea were also recorded.Results:A total of 320 patients were enrolled in the study, including 188 males (58.8%) and 132 females (41.2%), with a mean age of (50±13) years. The duration of surgery was (38.6±30.1) minutes, anesthesia time was (57.2±32.8) minutes, and stay time in PACU was (34.6±11.4) minutes. There were 115, 141, and 64 patients in the rocuronium bromide, mivacurium chloride, and cisatracurium groups, respectively. The differences in age, body mass index, and ASA grade in patients among the 3 groups were not significant (all P>0.05). The anesthesia time and duration of surgery in patients of the mivacurium chloride group were shorter than those of the rocuronium bromide and cisatracurium groups [(43.53±23.90) minutes vs. (67.54±37.72) minutes and (68.84±29.34) minutes; (26.87±22.18) minutes vs. (47.16±34.83) minutes and (48.84±27.57) minutes], and the differences were statistically significant (all P<0.01). The difference in stay time in PACU among the 3 groups was not statistically significant ( P>0.05). At the moment of entering PACU, 272 (88.6%) of 320 patients had TOFr<0.9, of which 105 (32.8%) had TOFr<0.7; when leaving PACU, the TOFr of all patients was>0.9. Except the time point of leaving PACU, TOFr in the rocuronium bromide group at the other time points were higher than those in the cisatracurium group (all P<0.01). Except the 2 time points of the moment of entering and leaving PACU, TOFr in the mivacurium chloride group was higher than those in the cisatracurium group (all P<0.01). At the moment of entering PACU and 5 minutes after entering PACU, TOFr in the mivacurium chloride group was lower than those in the rocuronium bromide group (all P<0.05). When entering PACU, 79 of 320 patients had saturation of pulse oximetry (SpO 2)<0.95 and the difference in SpO 2 among the 3 groups was statistically significant ( P=0.029), of which 4 cases (6.25%) had SpO 2<0.90 in the cisatracurium group, and the incidence of hypoxemia was higher than that in the other 2 groups. The differences in ability of speach and head lifting of patients among the 3 groups when entering PACU were statistically significant ( P=0.036, P<0.001). No adverse events such as reflux, or aspiration, dyspnea occurred in patients in PACU. Conclusions:The incidence of RNMB in patients undergoing laryngeal surgery entering PACU immediately is high and the degree of RNMB is more severe, with TOFr gradually increasing and RNMB decreasing over time. The patients who receive cisatracurium have a high incidence and severity of postoperative RNMB. Routine monitoring and neuromuscular monitoring in PACU are beneficial for patients′ perioperative safety.

Background::Acute kidney injury (AKI) is a common complication in patients, especially elderly patients, who undergo cardiac surgery with cardiopulmonary bypass. Studies have indicated a protective role of autophagy in AKI. However, the mechanisms underlying the regulatory effect of autophagy in AKI among patients undergoing cardiac surgeries are poorly understood. In this study, we aimed to test the hypothesis that exosomal microRNAs (miRNAs) regulate autophagy in tubular epithelial cells after AKI.Methods::Plasma exosomal RNA was extracted from young and elderly AKI patients undergoing cardiac surgery, and the miRNAs expression during the perioperative period were analyzed using next-generation sequencing. The screened miRNAs and their target genes were subjected to gene oncology function and Kyoto Encyclopedia of Genes and Genome enrichment analyses. Renal tubular epithelial cell line (HK-2 cells) was cultured and hypoxia/reoxygenation (H/R) model was established, which is an in vitro renal ischemia/reperfusion (I/R) model. We used Western blot analysis, cell viability assay, transfection, luciferase assay to investigate the mechanisms underlying the observed increases in the levels of renal I/R injury-mediated exosomal miRNAs and their roles in regulating HK-2 cells autophagy. Results::miR-590-3p was highly enriched in the plasma exosomes of young AKI patients after cardiac surgery. Increased levels of miR-590-3p led to the increases in the expression of autophagy marker proteins, including Beclin-1 and microtubule associated protein 1 light chain 3 beta (LC3II), and prolonged the autophagic response in HK-2 cells after H/R treatment. These effects were achieved mainly via increases in the exosomal miR-590-3p levels, and the tumor necrosis factor receptor-associated factor 6 protein was shown to play a key role in I/R injury-mediated autophagy induction.Conclusion::Exosomes released from HK-2 cells after renal I/R injury regulate autophagy by transferring miR-590-3p in a paracrine manner, which suggests that increasing the miR-590-3p levels in HK-2 cell-derived exosomes may increase autophagy and protect against kidney injury after renal I/R injury.