Dezocine relieves the postoperative hyperalgesia in rats through suppressing the hyper-action of Akt1/GSK-3ß pathway.

The relieving role of dezocine in pain after surgery was previously reported, while the potential mechanism was not completely clear. Therefore, the current research probed into the regulatory mechanism of dezocine in pain after surgery. A postoperative pain model was established by performing plantar incision surgery on the juvenile Sprague-Dawley rats. After the rats were treated with dezocine or SC79 (Akt1 activator), the paw withdrawal threshold and paw withdrawal latency of rats were detected to evaluate the mechanical allodynia and thermal hyperalgesia. After the plantar tissue, dorsal root ganglions, and spinal cord of rats were collected, the expressions of Akt1, p-Akt1, GSK-3ß, and p-GSK-3ß in the tissues were determined by western blot to evaluate the activation state of the Akt1/GSK-3ß pathway. After surgery, the paw withdrawal threshold and paw withdrawal latency of rats were lessened, whereas the ratios of p-Akt1/Akt1 and p-GSK-3ß/GSK-3ß were augmented in rat plantar tissue, dorsal root ganglions, and spinal cord. After treatment with dezocine alone, the paw withdrawal threshold and paw withdrawal latency of postoperative rats were elevated, but ratios of p-Akt1/Akt1 and p-GSK-3ß/GSK-3ß were reduced. After co-treatment with dezocine and SC79, SC79 reversed the effects of dezocine on elevating the paw withdrawal threshold and paw withdrawal latency, and reducing the ratios of p-Akt1/Akt1 and p-GSK-3ß/GSK-3ß in postoperative rats. Dezocine ameliorated the postoperative hyperalgesia in rats via repressing the hyper-action of Akt1/GSK-3ß pathway.

Risk Factors for Fentanyl-Induced Cough Following General Anesthesia in Adults: A Retrospective Study from a Single Center in China.

BACKGROUND Fentanyl-induced cough (FIC) during general anesthesia induction and postoperative nausea and vomiting are common complications, yet the risk factors for FIC remain controversial. This retrospective study was conducted at a single center in China and aimed to investigate the risk factors for fentanyl-induced cough following general anesthesia in adults. MATERIAL AND METHODS A total of 601 adult patients undergoing elective surgery were enrolled, and the incidence of FIC during general anesthesia induction and postoperative adverse events were recorded. The risk factors for FIC during general anesthesia induction and postoperative nausea and vomiting were assessed using multivariate logistic regression analysis. RESULTS The incidence of FIC, nausea, and vomiting were 21.8%, 6.3%, and 4.5%, respectively. The results of multivariate logistic regression analysis indicated that pharyngitis history was associated with an increased risk of FIC during general anesthesia induction (odds ratio [OR]: 2.852; 95% confidence interval [CI]: 1.698-4.792; P<0.001), whereas use of lidocaine could protect against FIC risk (OR: 0.649; 95% CI: 0.557-0.757; P<0.001). However, the characteristics of patients were not associated with the risk of postoperative nausea and vomiting. CONCLUSIONS The findings from this study showed that a history of pharyngitis increased the risk of FIC, while the use of lidocaine was associated with a reduced risk of FIC. The risk of postoperative nausea and vomiting was not affected by fentanyl use or patient characteristics.

Effect of Inhibiting p38 on HuR Involving in ß-AChR Post-transcriptional Mechanisms in Denervated Skeletal Muscle.

Previous studies reported that RNA-binding protein human antigen R (HuR) mediates changes in the stability of AChR ß-subunit mRNA after skeletal muscle denervation; also, p38 pathway regulated the stability of AChR ß-subunit mRNA in C2C12 myotubes. However, the relationship between HuR and p38 in regulating the stability of AChR ß-subunit mRNA have not been clarified. In this study, we wanted to examine the effect of inhibiting p38 on HuR in denervated skeletal muscle. Denervation model was built and 10% DMSO or SB203580 were administered respectively follow denervation. Tibialis muscles were collected in 10% DMSO-administered contralateral (undenervated) leg, 10% DMSO-administered denervated leg, SB203580-administered contralateral (undenervated) leg, and SB203580-administered denervated leg, respectively. P38 protein, ß-AChR mRNA and protein, HuR protein, ß-AChR mRNA stability, and HuR binding with AChR ß-subunit mRNAs were measured. Results demonstrated that the administration of SB203580 can inhibit the increase of ß-AChR protein expression and mRNA expression and stability, and RNA-binding protein human antigen R (HuR) expression, in cytoplasmic and nuclear fractions in skeletal muscle cells following denervation. Importantly, we observed that SB203580 also inhibited the increased level of binding activity between HuR and AChR ß-subunit mRNAs following denervation. Collectively, these results suggested that inhibition of p38 can post-transcriptionally inhibit ß-AChR upregulation via HuR in denervated skeletal muscle.

Neuregulin-1ß attenuates sepsis-induced diaphragm atrophy by activating the PI3K/Akt signaling pathway.

The aim of this study was to investigate the protective effects of neuregulin-1ß (NRG-1ß) on sepsis-induced diaphragm atrophy and the possible underlying mechanisms. Sprague-Dawley rats were randomly divided into sham, sepsis and NRG groups. Sepsis was induced by cecal ligation and puncture (CLP). In the NRG group, rats received tail vein injections of NRG-1ß (10 µg/kg) every 12 h for 72 h after CLP. At 3 days after surgery, diaphragm contractile forces were measured by determining the force-frequency curve and muscle fiber areas by hematoxylin-eosin staining. Moreover, the NRG-1 expression level in the diaphragm was detected by Western blotting. Furthermore, the proteins in the PI3K/Akt signaling pathway and its downstream Akt-mTOR and Akt-FOXO axes were detected by Western blotting analysis. In L6 myotubes treated with lipopolysaccharide (LPS) and NRG-1ß, PI3K/Akt signaling pathway-related protein expression was further determined using the PI3K inhibitor LY294002. Exogenous NRG-1ß could compensate for sepsis-induced diminished NRG-1 in the diaphragm and attenuate the reduction in diaphragm contractile forces and muscle fiber areas during sepsis. Moreover, NRG-1ß treatment could activate the PI3K/Akt signaling pathway in the diaphragm during sepsis. The inhibition of p70S6K and 4E-BP1 on the Akt-mTOR axis and the increased expression of Murf1 on the Akt-FOXO axis were reversed after NRG-1 treatment. In addition, NRG-1ß could activate the PI3K/Akt signaling pathway in L6 myotubes treated with LPS, while the PI3K inhibitor LY294002 blocked the effects of NRG-1ß. NRG-1 expression in the diaphragm was reduced during sepsis, and exogenously administered recombinant human NRG-1ß could attenuate sepsis-induced diaphragm atrophy by activating the PI3K/Akt signaling pathway.

γ-Acetylcholine Receptor Mediating Dynamic Changes of Resistance to Rocuronium in the Denervated Skeletal Muscle.

BACKGROUND/AIMS: Denervation resulted in resistance to non-depolarizing muscle relaxants (NDMRs), the magnitude of which changed after denervation in the skeletal muscle. The aim of this study was to investigate whether changed potencies of rocuronium were due to altered γ-acetylcholine receptor (γ-AChR) expression after skeletal muscle denervation. METHODS: Innervated and denervated muscle cells were used in this study. Patch clamp and Western blotting techniques were separately applied to examine IC50 values of rocuronium and γ-AChR protein expression at different times after denervation. Then, using the linear Pearson correlation analysis, the relationship between IC50 values of rocuronium and γ-AChR expression was tested. RESULTS: Compared with the innervated control, both IC50 values of rocuronium and γ-AChR expression significantly increased at Day 4, 7, and 14 after denervation in the skeletal muscle. Furthermore, γ-AChR protein and IC50 values of rocuronium exibited a significant positive correlation (r = 0.7678, p < 0.0001). CONCLUSION: These above results indicated that dynamic changes of resistance to NDMRs may be due to altered γ-AChR expression after skeletal muscle denervation.

A single dose of dezocine suppresses emergence agitation in preschool children anesthetized with sevoflurane-remifentanil.

BACKGROUND: Emergence agitation (EA) is a common phenomenon in preschool children during emergence from general anesthesia. This study evaluated the safety and efficacy of dezocine for emergence agitation in preschool children anesthetized with sevoflurane-remifentanil. METHODS: A total of 100 preschool children, scheduled for elective laparoscopic repair of an inguinal hernia by high ligation of the hernia sac under sevoflurane-remifentanil anesthesia were randomized into two groups: Group C (n = 50) received Ringer's lactate 10 mL and Group D received Ringer's lactate 10 mL containing dezocine 0.1 mg/kg, postoperatively. RESULTS: Incidence of EA, defined as a score ≥ 3 on Aono's four point scale or Pediatric Anesthesia Emergence Delirium (PAED) score ≥ 10 in the PACU (10% vs. 76%) and the percentage of patients with severe EA (PAED score ≥ 13) (12% vs. 76%) were significantly lower in Group D compared to Group C (P < 0.05). Mean Children and Infants Postoperative Pain Scale (CHIPPS) score was significantly lower in Group D compared to Group C (1.2 ± 0.5 vs. 5.2 ± 0.6; P < 0.05). Patients need for fentanyl (18% vs. 4%) or propofol rescue (20% vs. 0) was significantly greater in Group C compared to Group D. No significant differences in other relative aspects after surgery between groups. CONCLUSION: Administration of dezocine 0.1 mg/kg decreased the incidence and severity of EA in preschool children that had undergone laparoscopic repair of an inguinal hernia by high ligation of the hernia sac under sevoflurane-remifentanil anesthesia. TRIAL REGISTRATION: A single dose of dezocine suppresses emergence agitation in preschool children anesthetized with sevoflurane-remifentanil effectively: A double-blind, prospective, randomized, controlled study, Chinese Clinical Trial Registry (ID: ChiCTR-IOR-16010033), retrospectively registered on November 21, 2016.

[The Role of DNA Double-strain Damage Repairing Mechanisms in Diabetic Atheroscolersis].

OBJECTIVES: To identify the role of DNA double-strain damage repairing pathway in the development of diabetics atherosclerosis. METHODS: Wistar male rats were randomly divided into three groups: control group (group A), balloon injury group (group B) and diabetes + balloon injury group (group C). Streptozotocin (STZ) was injected into rat abdomen to induce diabetes. After stabilizing high glucose, rats in group B and group C were both under aortic balloon injury technique and fed high lipid forage post-operatively. Glucose levels and weight were observed weekly. Segments of aortoa of three groups were taken at 2, 4, 6 and 8 weeks, staining of senescent ß-galactosidase (SA-ß-gal) staining, HE and changes of aorta under light microscope were observed. The area of tunica intima (I) and tunica media (M) in aorta was measured, and their ratio (I/M) were analyzed. Expressions of gamma-histong family 2A variant (γ-H2AX), phosphorylated ataxia telangiectasia mutated (ATM), phosphorylated checkpoint kinasen 2 (CHK2) and phosphorylated P53 were detected by immunohistochemical staining. RESULTS: SA-ß-gal staining positive areas were dotted around in group B and group C [CM(155.3mm]but not in group A at two weeks.At the same time, a slight hyperlasia of aortic neointima was observed in HE staining of group B and group C. SA-ß-gal staining was positive scattered within the tunica intima of aorta of group B and group C at four weeks, and HE staining promted a significantly greater of aortic neointima in the group C than that in the other two group (P<0.05). Positive regions of SA-ß-gal staining were more in group C than group B at six weeks. Typical atherosclerotic plaques were formed, vascular smooth muscle cells were disordered arranged and foam cells were aggregated in the plaques of group C at six weeks post-operatively, and intimal membrane areas increased than group A and group B (P <0.05). At 8 weeks, SA-ß-gal positive areas in group C were greater than in group B. The arteriolar wall was markedly thickened and the lumen was narrowed. The area of intimal membrane and the I/M radio were significantly greater in group C than those in group A and group B (P <0.05). Positive expressed of γ-H2AX, phosphorylated ATM, phosphorylated CHK2 and phosphorylated P53 were observed in typical atherosclerotic foci of group C, and weaker expressed in group B. CONCLUSION: Cellular senescence of vascular edothelium is triggered and DNA double-strain damage is increased in diabetes. The DNA double-strain damage repairing machines may participate in the development of diabetic atherosclerosis.

Slowed relaxation of diaphragm in septic rats is associated with reduced expression of sarco-endoplasmic reticulum CA2+ -ATPase genes SERCA1 and SERCA2.

INTRODUCTION: The aim of this study was to study the effects of sepsis on diaphragm relaxation properties and the associated expression of sarco-endoplasmic reticulum Ca2+ -ATPase genes SERCA1 and SERCA2. METHODS: Rats were randomized to undergo either sham surgery or cecal ligation and puncture (CLP). Diaphragm isometric relaxation parameters were measured after 24 h. The mRNA expression and protein content of SERCA1 and SERCA2 in diaphragm muscles were determined. RESULTS: Both diaphragm maximal twitch and tetanus relaxation rates were reduced. Twitch half-relaxation time was prolonged after normalization to half of peak twitch tension. The mRNA expression and protein content of SERCA1 and SERCA2 were decreased. CONCLUSIONS: Slowed relaxation of the diaphragm in septic rats was associated with reduced expression of SERCA1 and SERCA2. Muscle Nerve 54: 1108-1113, 2016.

Beneficial effects of dantrolene on sepsis-induced diaphragmatic dysfunction are associated with downregulation of high-mobility group box 1 and calpain-caspase-3 proteolytic pathway.

BACKGROUND: Intracellular calcium overload is a major contributing factor to diaphragmatic dysfunction triggered by sepsis. In this study, the possible role of dantrolene, a ryanodine receptor inhibitor, in preventing the release of calcium from the sarcoplasmic reticulum in diaphragmatic dysfunction and weakness was explored. METHODS: A middle-grade severity sepsis rat model was established for the effects of treatment with dantrolene, on diaphragm harvested 24 h after cecal ligation and puncture (CLP), and analyzed using functional, histologic, and biomarker assays. RESULTS: It was found that in septic rats, treatment with dantrolene significantly improved the contractility, relaxation, and fatigue index of the diaphragm in a dose-dependent manner. The benefits are associated with improvement in ultrastructural changes of Z band integrity and myofilament arrangements along with increases both in the ratio of slow-twitch type composition. Moreover, dantrolene effectively inhibits the overexpression of high-mobility group box 1 and reduces the calpain-1-caspase-3 proteolytic activity. CONCLUSIONS: Dantrolene can effectively attenuate the dysfunction of diaphragm in septic rats; Furthermore, the beneficial effects were associated with downregulation of high-mobility group box 1 and calpain-1-caspase-3 proteolytic activity.

Receptor analysis of differential sensitivity change to succinylcholine induced by nerve injury in rat gastrocnemius.

BACKGROUND: Urgent tracheal intubation is common in intensive care units and the emergency room, and succinylcholine is a first-line neuromuscular blocker used in these situations. Paraplegic or critically ill patients may be at a high risk of receiving succinylcholine because the denervation stage changes nicotinic receptors, which affect the efficacy and safety of succinylcholine. The objective of this study was to determine the receptor subtypes associated with changes in the pharmacodynamics of succinylcholine and its time-line trend. METHODS: Denervated gastrocnemius was collected from tibial nerve transected rats. To determine the 50% effective dose of succinylcholine and rocuronium at 0 (control), 1, 3, 7, 14, and 28 d after denervation, action potential amplitude was monitored by an intracellular recording method. Subunits α1, α7, ε, and γ of the acetylcholine receptor (AChR) were quantified by real-time polymerase chain reaction. Receptor amount and pharmacodynamic changes were analyzed by correlation and regression analysis. RESULTS: The pharmacodynamic change in succinylcholine was a dynamic process, and at the same time α7, ε, and γ-nicotinic AChR genes in denervated muscle were significantly changed but only α7 was closely correlated with the action of succinylcholine. Subunit γ and α7 were related to pharmacodynamic change in the nondepolarizing neuromuscular agent, rocuronium. CONCLUSIONS: Nerve injury may alter nicotinic AChR subtypes in skeletal muscle at different stages, which probably affected the pharmacodynamics of neuromuscular blockers in different ways. Denervation time and stage and the type of neuromuscular blocker and dosage should be taken into consideration when using these drugs in patients with nerve injury.

The effect of infraorbital nerve block on emergence agitation in children undergoing cleft lip surgery under general anesthesia with sevoflurane.

BACKGROUND: Sevoflurane is widely used in pediatric anesthesia. However, a high incidence of emergence agitation (EA) after general anesthesia with sevoflurane has been reported and pain has been regarded as a significant contributing factor. The objective of this prospective randomized, placebo-controlled trial was to determine whether infraorbital nerve block reduces EA in children undergoing repair of cleft lip after sevoflurane. METHODS: In this randomized, placebo-controlled trial, we enrolled 110 children (5 months to 6 years of age), who were scheduled for cleft lip surgery, and randomized them to the following two groups: Group S and Group B, where 1.5 ml saline (Group S) or 1.5 ml 0.25% bupivacaine (Group B) were administered in the infraorbital foramen. Emergence behavior was assessed in the postanesthesia care unit using the Pediatric Anesthesia Emergence Delirium (PAED) scale and a 5-point scale described by Cole. Pain was evaluated using the Children and Infants Postoperative Pain Scale (CHIPPS). RESULTS: One-hundred children (n = 50 per group) completed the study. The endtidal concentration of sevoflurane in Group B was lower than that in Group S. The incidence of EA was 16% in Group B and 42% in Group S (P = 0.008). The PAED scale score in Group B (mean [95% CI] 9 [8-12]) was lower than that in Group S (11.5 [9.8-15]). The duration of EA in Group B was shorter than that in Group S. CHIPPS score in postanesthetic care unit were lower in Group B (mean [95% CI] 3 [2-3.3]) compared with that in Group S (5 [4-6]). CONCLUSION: In children undergoing cleft lip repair surgery, infraorbital nerve block at the beginning of surgery significantly decreased the incidence of EA and the duration of EA, and provided satisfactory postoperative analgesia without delaying the time to extubation with sevoflurane anesthesia.

Denervation stage differentially influences resistance to neuromuscular blockers in rat gastrocnemius.

BACKGROUND: Muscle denervation was common in clinical surgery patients, which was mostly caused by trauma, paraplegia, and other factors. Denervated muscle in patients could lead to significant differential reaction to neuromuscle blockers due to the time of denervation and affected muscle area. We tested the hypothesis that resistance to non-depolarizing muscle relaxants (NDMRs) changes with time, and is related to the expression of immature and total acetylcholine receptors (AChRs). MATERIALS AND METHODS: The study evaluated the effect change of neuromuscular blockers in tibial nerve transected rat model. To determine 50% effective dose of NDMRs and succinycholine at 1, 7, 14, 28, and 35 days after denervation, action potential amplitude was monitorted by intracellular recording method. The messenger DNA that encodes the AChR-γ and AChR-ε subunits and the protein of the -γ and -ε subunits were quantified in the gastrocnemius by reverse transcription-polymerase chain reaction and western blotting respectively. Receptor number and pharmacodynamic changes was analyzed by correlation and regression analysis. RESULTS: Increased AChR-γ correlated with total AChRs, suggesting that the up-regulated AChRs may contain the immature isoform. The 50% effective dose of vecuronium and atracurium increased 1.2- to 1.5-fold at all time periods and correlated significantly with AChRs and AChR-γ. CONCLUSIONS: After denervation, resistance to NDMRs occurred earlier, was more marked from 14 days, and changes in resistance to NDMRs in skeletal muscle after nerve injury is dependent on the level of expression of immature and total AChRs. Denervation time should be of concern when such patients undergo surgery.

Cerebral protective effect of nicorandil premedication on patients undergoing liver transplantation.

BACKGROUND: Neurological injury is a common complication in the early period after liver transplantation, posing an enormous obstacle to treatment efficiency and patient survival. Nicorandil is a mitochondrial ATP-sensitive potassium channel (mitoKATP) opener. It has been reported to be effective in reducing brain injury in recent studies. However, it is still unclear whether nicorandil has cerebral protective effect in patients undergoing liver transplantation. METHODS: Fifty patients scheduled for liver transplantation were randomly divided into a nicorandil group (group N) (n=25), in which patients received 10 mg nicorandil through a nasogastric tube 30 minutes before induction of anesthesia, and a control group (group C) (n=25) who received 10 mL normal saline. The Mini-Mental State Examination (MMSE) was performed before anesthesia (day 0), and on days 3 and 7 after surgery. Blood samples were obtained before induction of anesthesia (T1), and at 12 (T2) and 36 hours (T3) after surgery for determination of serum neuron-specific enolase (NSE) and S100ß protein (S100ß) concentrations. RESULTS: During surgery, 5 patients in each group were eliminated due to severe reperfusion or renal insufficiency. Therefore, 20 patients remained in each group. The MMSE scores after operation were significantly lower than those before operation in group C. However, there was no difference at days 3 and 7 compared with day 0 in group N. Serum NSE concentrations after surgery were significantly higher than baseline (at T1) in both groups, except at T3 in group N. Serum S100ß concentration after surgery was significantly higher than baseline (at T1) in both groups. The MMSE scores at days 3 and 7 in group N were significantly higher than those in group C. The concentrations of serum NSE and S100ß at T2 and T3 in group N were significantly lower than those in group C. CONCLUSIONS: Oral nicorandil, as a premedication before liver transplantation, improves postoperative MMSE scores. It also attenuates the increase of NSE and S100ß in blood, indicating its cerebral protective effect.

Synthesis, Biological Evaluation, and Molecular Docking Studies of Hydrazones as Novel Xanthine Oxidase Inhibitors.

A series of hydrazones, 2-cyano-N'-(4-diethylamino-2-hydroxybenzylidene)acetohydrazide (1), N'-(5-bromo-2-hydroxy-3-methoxybenzylidene)-3-chlorobenzohydrazide monohydrate (2·H2O), N'-(2-hydroxy-3-methylbenzylidene)-4-nitrobenzohydrazide (3), and N'-(2-hydroxy-3-trifluoromethoxybenzylidene)-4-nitrobenzohydrazide (4), were prepared and structurally characterized by elemental analysis, IR and 1H NMR spectra, and single crystal X-ray determination. Xanthine oxidase inhibitory activities of the compounds were studied. Among the compounds, 2-cyano-N'-(4-diethylamino-2-hydroxybenzylidene)acetohydrazide shows the most effective activity. Docking simulation was performed to insert the compounds into the crystal structure of xanthine oxidase at the active site to investigate the probable binding modes.

Magnesium sulfate enhances non-depolarizing muscle relaxant vecuronium action at adult muscle-type nicotinic acetylcholine receptor in vitro.

AIM: To investigate the effect of magnesium sulfate and its interaction with the non-depolarizing muscle relaxant vecuronium at adult muscle-type acetylcholine receptors in vitro. METHODS: Adult muscle-type acetylcholine receptors were expressed in HEK293 cells. Drug-containing solution was applied via a gravity-driven perfusion system. The inward currents were activated by brief application of acetylcholine (ACh), and recorded using whole-cell voltage-clamp technique. RESULTS: Magnesium sulfate (1-100 mmol/L) inhibited the inward currents induced ACh (10 µmol/L) in a concentration-dependent manner (IC(50)=29.2 mmol/L). The inhibition of magnesium sulfate was non-competitive. In contrast, vecuronium produced a potent inhibition on the adult muscle-type acetylcholine receptor (IC(50)=8.7 nmol/L) by competitive antagonism. Magnesium sulfate at the concentrations of 1, 3, and 6 mmol/L markedly enhanced the inhibition of vecuronium (10 nmol/L) on adult muscle-type acetylcholine receptors. CONCLUSION: Clinical enhancement of vecuronium-induced muscle relaxation by magnesium sulfate can be attributed partly to synergism between magnesium sulfate and non-depolarizing muscle relaxants at adult muscle-type acetylcholine receptors.

Identification of independent risk factors for intraoperative gastroesophageal reflux in adult patients undergoing general anesthesia.

BACKGROUND: Gastroesophageal reflux (GER) affects up to 20% of the adult population and is defined as troublesome and frequent symptoms of heartburn or regurgitation. GER produces significantly harmful impacts on quality of life and precipitates poor mental well-being. However, the potential risk factors for the incidence and extent of GER in adults undergoing general anesthesia remain unclear. AIM: To explore independent risk factors for the incidence and extent of GER during general anesthesia induction. METHODS: A retrospective study was conducted, and 601 adult patients received general anesthesia intubation or laryngeal mask surgery between July 2016 and January 2019 in Shanghai General Hospital of Nanjing Medical University. This study recruited a total of 601 adult patients undergoing general anesthesia, and the characteristics of patients and the incidence or extent of GER were recorded. The potential risk factors for the incidence of GER were explored using multivariate logistic regression, and the risk factors for the extent of GER were evaluated using multivariate linear regression. RESULTS: The current study included 601 adult patients, 82 patients with GER and 519 patients without GER. Overall, we noted significant differences between GER and non-GER for pharyngitis, history of GER, other digestive tract diseases, history of asthma, and the use of sufentanil (P < 0.05), while no significant differences between groups were observed for sex, age, type of surgery, operative time, body mass index, intraoperative blood loss, smoking status, alcohol intake, hypertension, diabetes mellitus, psychiatric history, history of respiratory infection, history of surgery, the use of lidocaine, palliative strategies, propofol, or rocuronium bromide, state anxiety inventory, trait anxiety inventory, and self-rating depression scale (P > 0.05). The results of multivariate logistic regression indicated that female sex [odds ratio (OR): 2.702; 95% confidence interval (CI): 1.144-6.378; P = 0.023], increased age (OR: 1.031; 95%CI: 1.008-1.056; P = 0.009), pharyngitis (OR: 31.388; 95%CI: 15.709-62.715; P < 0.001), and history of GER (OR: 11.925; 95%CI: 4.184-33.989; P < 0.001) were associated with an increased risk of GER, whereas the use of propofol could protect against the risk of GER (OR: 0.942; 95%CI: 0.892-0.994; P = 0.031). Finally, age (P = 0.004), operative time (P < 0.001), pharyngitis (P < 0.001), history of GER (P = 0.024), and hypertension (P = 0.017) were significantly associated with GER time. CONCLUSION: This study identified the risk factors for GER in patients undergoing general anesthesia including female sex, increased age, pharyngitis, and history of GER.

Potency of nondepolarizing muscle relaxants on muscle-type acetylcholine receptors in denervated mouse skeletal muscle.

AIM: to investigate the changing resistance to nondepolarizing muscle relaxants (NDMRs) during the first month after denervation. METHODS: the denervated and innervated skeletal muscle cells were examined on days 1, 4, 7, 14, 21, and 28 after denervation. Individual denervated and innervated cells were prepared from the flexor digitorum brevis of the surgically denervated and contralateral hind feet, respectively. Nicotinic acetylcholine receptors (nAChRs) in the cells were activated with 30 micromol/L acetylcholine, either alone or in combination with various concentrations of vecuronium. Currents were recorded using a whole-cell patch-clamp technique. RESULTS: the concentrations of vecuronium resulting in half-maximal inhibitory responses (IC(50)) increased 1.2- (P>0.05), 1.7-, 3.7-, 2.5-, 1.9-, and 1.8-fold (P<0.05) at Days 1, 4, 7, 14, 21, and 28 after denervation, respectively, compared to the innervated control. Resistance to vecuronium appeared at Day 4, peaked at Day 7, and declined at Day 14 after denervation. Nevertheless, IC(50) values at Day 28 remained significantly higher than those for the innervated control, suggesting that the resistance to vecuronium had not disappeared at Day 28. CONCLUSION: The NDMR doses required to achieve satisfactory clinical effects differ at different times after muscle denervation.

Different magnitude of resistance to nondepolarizing muscle relaxants in the denervated mouse skeletal muscle.

AIM: To test the hypothesis that different magnitude of resistance of denervated skeletal muscle to nondepolarizing muscle relaxants (NDMRs) is related to their varying potencies at epsilon-AChR and gamma-AChR. METHODS: Both innervated and denervated mouse muscle cells, and human embryonic kidney 293 (HEK293) cells expressing epsilon-AChR or gamma-AChR were used. The effects of NDMRs on nAChR were explored using whole-cell patch clamp technique. RESULTS: NDMRs vecuronium (VEC), atracurium (ATR) and rocuronium (ROC) produced reversible, dose-dependent inhibition on the currents induced by 30 micromol/L acetylcholine both in innervated and denervated skeletal muscle cells. Compared to those obtained in innervated skeletal muscle cells, denervation shifted the concentration-response curves rightward and significantly increased the 50% inhibitory concentration (IC(50)) values (VEC: from 11.2 to 39.2 nmol/L, P<0.01; ATR: from 24.4 to 129.0 nmol/L, P<0.01; ROC: from 37.9 to 101.4 nmol/L, P<0.01). In HEK293 cell expression system, ATR was less potent at gamma-AChR than epsilon-AChR (IC(50) values: 35.9 vs 22.3 nmol/L, P<0.01), VEC was equipotent at both receptor subtypes (IC(50) values: 9.9 vs 10.2 nmol/L, P>0.05), while ROC was more potent at gamma-AChR than epsilon-AChR (IC(50) values: 22.3 vs 33.5 nmol/L, P<0.05). CONCLUSION: Magnitude differences of resistance to different NDMRs caused by denervation are associated with distinct potencies of NDMRs at nAChR subtypes.

Neuregulin-1ß Protects the Rat Diaphragm during Sepsis against Oxidative Stress and Inflammation by Activating the PI3K/Akt Pathway.

Sepsis-induced diaphragm dysfunction (SIDD) which is mainly characterized by decrease in diaphragmatic contractility has been identified to cause great harms to patients. Therefore, there is an important and pressing need to find effective treatments for improving SIDD. In addition, acetylcholinesterase (AChE) activity is a vital property of the diaphragm, so we evaluated both diaphragmatic contractility and AChE activity. Though neuregulin-1ß (NRG-1ß) is known to exert organ-protective effects in some inflammatory diseases, little is known about the potential of NRG-1ß therapy in the diaphragm during sepsis. Our study was aimed at exploring the effects of NRG-1ß application on diaphragmatic contractility and AChE activity during sepsis. Proinflammatory cytokines, muscle injury biomarkers in serum, contractile force, AChE activity, proinflammatory cytokines, oxidative parameters, histological condition, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, and expression of phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB/Akt) signaling proteins in the diaphragm were measured and compared between nonseptic and septic groups with or without NRG-1ß treatment. In vitro, the effects of NRG-1ß on reactive oxygen species (ROS) production in the lipopolysaccharide- (LPS-) stimulated L6 rat muscle skeletal cells with or without the Akt inhibitor MK-2206 were detected. NRG-1ß inhibited proinflammatory cytokine release and muscle injury biomarkers soaring in serum and improved the sepsis-induced diaphragm dysfunction and AChE activity decrease significantly during sepsis. Meanwhile, the inflammatory response, oxidative stress, pathological impairment, and cell apoptosis in the diaphragm were mitigated by NRG-1ß. And NRG-1ß activated the PI3K/Akt signaling in the diaphragm of septic rats. Elevated ROS production in the LPS-stimulated L6 rat skeletal muscle cells was reduced after treatment with NRG-1ß, while MK-2206 blocked these effects of NRG-1ß. In conclusion, our findings underlined that NRG-1ß could reduce circulating levels of proinflammatory cytokines in rats with sepsis, adjust diaphragmatic proinflammatory cytokine level, mitigate diaphragmatic oxidative injury, and lessen diaphragm cell apoptosis, thereby improving diaphragmatic function, and play a role in diaphragmatic protection by activating PI3K/Akt signaling.