Hydrogen alleviates impaired lung epithelial barrier in acute respiratory distress syndrome via inhibiting Drp1-mediated mitochondrial fission through the Trx1 pathway.

Acute respiratory distress syndrome (ARDS) is an acute and severe clinical complication lacking effective therapeutic interventions. The disruption of the lung epithelial barrier plays a crucial role in ARDS pathogenesis. Recent studies have proposed the involvement of abnormal mitochondrial dynamics mediated by dynamin-related protein 1 (Drp1) in the mechanism of impaired epithelial barrier in ARDS. Hydrogen is an anti-oxidative stress molecule that regulates mitochondrial function via multiple signaling pathways. Our previous study confirmed that hydrogen modulated oxidative stress and attenuated acute pulmonary edema in ARDS by upregulating thioredoxin 1 (Trx1) expression, but the exact mechanism remains unclear. This study aimed to investigate the effects of hydrogen on mitochondrial dynamics both in vivo and in vitro. Our study revealed that hydrogen inhibited lipopolysaccharide (LPS)-induced phosphorylation of Drp1 (at Ser616), suppressed Drp1-mediated mitochondrial fission, alleviated epithelial tight junction damage and cell apoptosis, and improved the integrity of the epithelial barrier. This process was associated with the upregulation of Trx1 in lung epithelial tissues of ARDS mice by hydrogen. In addition, hydrogen treatment reduced the production of reactive oxygen species in LPS-induced airway epithelial cells (AECs) and increased the mitochondrial membrane potential, indicating that the mitochondrial dysfunction was restored. Then, the expression of tight junction proteins occludin and zonula occludens 1 was upregulated, and apoptosis in AECs was alleviated. Remarkably, the protective effects of hydrogen on the mitochondrial and epithelial barrier were eliminated after applying the Trx1 inhibitor PX-12. The results showed that hydrogen significantly inhibited the cell apoptosis and the disruption of epithelial tight junctions, maintaining the integrity of the epithelial barrier in mice of ARDS. This might be related to the inhibition of Drp1-mediated mitochondrial fission through the Trx1 pathway. The findings of this study provided a new theoretical basis for the application of hydrogen in the clinical treatment of ARDS.

Effect of single intravenous injection of esketamine on postpartum depression after labor analgesia and potential mechanisms: a randomized, double-blinded controlled trial.

BACKGROUND: The study was designed to investigate effects of single intravenous injection of esketamine on the incidence of postpartum depression (PPD) after labor analgesia and explore the potential mechanisms. METHODS: A total of 120 women who underwent labor analgesia by epidural analgesia pump were enrolled and divided into two groups randomly. Esketamine at a dose of 0.2 mg/kg was intravenously injected after fetal disengagement in the test group and placebo was administered in the control group. The occurrence of PPD and side effects after delivery were recorded. Some indicators related to stress and inflammation were measured before labor analgesia and at 24 h, 1 week, and 6 weeks after delivery in this study. Data were analyzed by independent t-test, repeated measures analysis of variance and Chi-square test in SPSS software (version 25.0). It was considered statistically significant since a p value less than 0.05. RESULTS: The incidence of PPD was significantly decreased both for one week and six weeks after delivery by using of esketamine (3.4% vs. 15.3%, p = 0.004 and 5.2% vs. 18.6%, p = 0.006, respectively). There were also significant differences between the stress and inflammation-related indicators in different time points in this study, while the side effects for 48 h after delivery were similar between the two groups. CONCLUSIONS: Single intravenous injection of esketamine after delivery in participants underwent labor analgesia can decrease the occurrence of postpartum depression for one week and six weeks after delivery, while the side effects were not increased. The antidepressant effects of esketamine may be related to the reduction of stress response and inflammation. TRIAL REGISTRATION: The trial was registered at the Chinese Clinical Trial Registry on 5/30/2022 (CTRI registration number-ChiCTR2200060387). URL of registry: https://www.chictr.org.cn/bin/home .

Effect of pre-administration of esketamine intraoperatively on postpartum depression after cesarean section: A randomized, double-blinded controlled trial.

BACKGROUND: To evaluate the effect of pre-administration of esketamine intraoperatively on the occurrence of postpartum depression after cesarean section under combined spinal-epidural anesthesia. METHODS: A total of 120 women aged 24 to 36 years undergoing cesarean section by spinal-epidural anesthesia with American Society of Anesthesiologists physical status II were enrolled. According to the intraoperative use of esketamine, all participants were randomly divided into 2 groups: test group (group E) and control group (group C). Esketamine was administered intravenously at a dose of 0.2 mg/kg after the infant was delivered in group E and equal volume of normal saline was given in group C. The incidence of postpartum depression was recorded at 1 week and 6 weeks after the operation. The occurrence of adverse reactions such as postpartum bleeding, nausea and vomiting, drowsiness, and nightmares were also recorded at 48 hours after surgery. RESULTS: Compared with group C, the incidence of postpartum depression was significantly lower at 1 week and 6 weeks after surgery in group E (P < .01). There was no significant difference of the adverse effects at 48 hours after the operation between the 2 groups. CONCLUSION: Intravenous infusion of 0.2 mg/kg esketamine in women during cesarean section can significantly reduce the incidence of postpartum depression at 1 week and 6 weeks after surgery without increasing related adverse effects.

Effects of esketamine on analgesia and postpartum depression after cesarean section: A randomized, double-blinded controlled trial.

BACKGROUND: The aim of this randomized double-blind placebo controlled clinical trial was to investigate the effects of different doses of esketamine combined with sufentanil for postoperative intravenous controlled analgesia after cesarean section and the incidence of postpartum depression. METHODS: One hundred and sixty patients undergoing elective cesarean section, with a singleton term pregnancy and American Society of Anesthesiologists physical status II were selected. All patients were treated by a combined epidural with spinal anesthesia. They were randomly divided into 4 groups according to patient controlled intravenous analgesia formula. The consumption of sufentanil, times of effective press and remediate analgesia at 48 hours after cesarean section, incidence of postpartum depression (PPD) at 1 week and 6 weeks after the operation were recorded. RESULTS: Comparison of cumulated dosage of sufentanil, times of effective press and rescue analgesia at 48 hours after operation: Group H was significantly lower than Group M, Group L, and Group C (P < .05), Group M significantly lower than group L and Group C (P < .05), and Group L significantly lower than Group C (P < .05). Comparison of the incidence of PPD at 1 week and 6 weeks later: Group H was significantly lower than Group M, Group L, and Group C (P < .01), Group M significantly lower than Group L and Group C (P < .01) and Group L significantly lower than Group C (P < .01). Compared with Group C, the incidence of nausea and vomiting was significantly reduced in Group H, Group M, and Group L (P < .05). CONCLUSION: Esketamine combined with sufentanil used for patient controlled intravenous analgesia after elective cesarean section can reduce the consumption of sufentanil, improve postoperative analgesia, decrease the incidence of PPD at 1 week and 6 weeks and postoperative nausea and vomiting.

Biological evaluation of a novel bilirubin adsorbent and its therapeutic effect on animal models of hyperbilirubinemia.

Hyperbilirubinemia caused severe hepatobiliary diseases with various causes, especially hepatic fibrosis and cirrhosis caused by end-stage hepatitis B and C. Plasma adsorption perfusion (PP) has a tremendous advantage in treating patients with hyperbilirubinemia and liver failure, wherein, a safe and effective adsorbent is the key to filter out bilirubin successfully in PP. In this work, a simple engineering strategy, a new porous polymer adsorption resin ERM-0100 based on the homopolymer predispersion system, is proposed to produce high-performance bilirubin adsorbents. Preliminary experimental results show that ERM-0100 exhibits a large surface area and uniformly porous structure. Experimental results verify that ERM-0100 has high biocompatibility and bilirubin adsorption efficiency (TBIL:35%, direct bilirubin [DBIL]:30%, IBIL:87%) that is significantly higher than most of the reported adsorbents. Animal experiments prove that ERM-0100 has high bilirubin adsorption efficiency and can improve the liver function of animals. The combination of high biocompatibility and high adsorption capacity positions the ERM-0100 as a promising candidate for bilirubin removal.

Hydrogen Attenuates Endotoxin-Induced Lung Injury by Activating Thioredoxin 1 and Decreasing Tissue Factor Expression.

Endotoxin-induced lung injury is one of the major causes of death induced by endotoxemia, however, few effective therapeutic options exist. Hydrogen inhalation has recently been shown to be an effective treatment for inflammatory lung injury, but the underlying mechanism is unknown. In the current study we aim to investigate how hydrogen attenuates endotoxin-induced lung injury and provide reference values for the clinical application of hydrogen. LPS was used to establish an endotoxin-induced lung injury mouse model. The survival rate and pulmonary pathologic changes were evaluated. THP-1 and HUVECC cells were cultured in vitro. The thioredoxin 1 (Trx1) inhibitor was used to evaluate the anti-inflammatory effects of hydrogen. Hydrogen significantly improved the survival rate of mice, reduced pulmonary edema and hemorrhage, infiltration of neutrophils, and IL-6 secretion. Inhalation of hydrogen decreased tissue factor (TF) expression and MMP-9 activity, while Trx1 expression was increased in the lungs and serum of endotoxemia mice. LPS-stimulated THP-1 and HUVEC-C cells in vitro and showed that hydrogen decreases TF expression and MMP-9 activity, which were abolished by the Trx1 inhibitor, PX12. Hydrogen attenuates endotoxin-induced lung injury by decreasing TF expression and MMP-9 activity via activating Trx1. Targeting Trx1 by hydrogen may be a potential treatment for endotoxin-induced lung injury.

Effect of pre-administration with aminophylline on the occurrence of post-dural puncture headache in women undergoing caesarean section by combined spinal-epidural anaesthesia.

OBJECTIVE: To investigate the effect of the pre-administration with aminophylline on the occurrence of post-dural puncture headache (PDPH) in women undergoing caesarean section by combined spinal-epidural anaesthesia (CSEA). METHODS: The study enrolled women undergoing elective caesarean sections with CSEA and randomly allocated them into two groups; for 30 min immediately after the infant was delivered, group A received 250 mg aminophylline intravenously and group B received an equal volume of normal saline. Demographic data, operation time, intraoperative blood loss, intraoperative transfusion volume and the occurrence of PDPH during the first 7 days after the operation were recorded. Side-effects such as hypersensitivity, convulsion and arrhythmia were also recorded in the patients and infants in group A within 24 h after aminophylline administration. RESULTS: A total of 120 patients aged 24-38 years (pregnancy range, 38-42 weeks) were randomly allocated into two groups ( n = 60). The incidence of PDPH in group A was significantly lower than group C (two of 59 [3.4%] versus 10 of 58 [17.2%], respectively). There were no related side-effects within 24 h after aminophylline administration in group A. CONCLUSIONS: Intraoperative intravenous infusion of 250 mg aminophylline reduced the incidence of PDPH after caesarean section under CSEA with no side-effects.

Efficacy of phosphocreatine pre-administration on XIAP and Smac in ischemic penumbra of rats with focal cerebral ischemia reperfusion injury.

PURPOSE: To observe the efficacy of phosphocreatine pre-administration (PCr-PA) on X-linked inhibitor of apoptosis protein (XIAP), the second mitochondia-derived activator of caspase (Smac) and apoptosis in the ischemic penumbra of rats with focal cerebral ischemia-reperfusion injury (CIRI). METHODS: A total of 60 healthy male Sprague Dawley (SD) rats were randomly divided into three groups (n=20): group A (the sham operation group), group B <intraperitoneally injected with 20 mg/kg (10 mg/ml) of saline before preparing the ischemia-reperfusion (IR) model>, and group C <intraperitoneally injected with 20 mg/kg (10 mg/ml) of PCr immediately before preparing the IR model>. After 24 h for reperfusion, the neurological function was evaluated and the tissue was sampled to detect expression of XIAP, Smac and caspase-3 positive cells in the ischemic penumbra so as to observe the apoptosis. RESULTS: Compared with group B, neurological deficit scores, numbers of apoptotic cells, expression of Smac,caspase-9 and the numbers of Caspase-3 positive cells were decreased while expression of XIAP were increased in the ischemic penumbra of group C. CONCLUSIONS: Phosphocreatine pre-administration may elicit neuroprotective effects in the brain by increasing expression of X-linked inhibitor of apoptosis protein, reducing expression of second mitochondia-derived activator of caspase, and inhibiting the apoptosis in the ischemic penumbra.

Oxycodone for prevention of etomidate-induced myoclonus: a randomized double-blind controlled trial.

Objective This study was performed compare the effectiveness of oxycodone and fentanyl in reducing the incidence and severity of etomidate-induced myoclonus. Methods In total, 162 patients with an American Society of Anesthesiologists physical status of I or II were assigned at random to three groups. Patients assigned to Group O received 0.1 mg/kg of oxycodone (n = 54), those assigned to Group F were given 1 µg/kg of fentanyl (n = 54), and those assigned to Group S were given an equal volume of saline intravenously 2 minutes prior to administration of 0.3 mg/kg of etomidate (n = 54). The incidence and severity of myoclonus was evaluated 2 minutes after etomidate administration. The patients' vital signs, coughing, nausea, dizziness, and other related adverse reactions were also recorded. Results The incidence of myoclonus was significantly lower in Group O (0.0%) than in Group F (31.5%) and Group S (72.2%); the intensity was also lowest in Group O. All patients in each group had stable cardiovascular profiles. Conclusions Intravenous injection of 0.1 mg/kg of oxycodone 2 minutes prior to etomidate is more effective in preventing etomidate-induced myoclonus during general anesthesia than is 1 µg/kg of fentanyl.

Efficacy of phosphocreatine pre-administration on XIAP and Smac in ischemic penumbra of rats with focal cerebral ischemia reperfusion injury

Abstract Purpose: To observe the efficacy of phosphocreatine pre-administration (PCr-PA) on X-linked inhibitor of apoptosis protein (XIAP), the second mitochondia-derived activator of caspase (Smac) and apoptosis in the ischemic penumbra of rats with focal cerebral ischemia-reperfusion injury (CIRI). Methods: A total of 60 healthy male Sprague Dawley (SD) rats were randomly divided into three groups (n=20): group A (the sham operation group), group B <intraperitoneally injected with 20 mg/kg (10 mg/ml) of saline before preparing the ischemia-reperfusion (IR) model>, and group C <intraperitoneally injected with 20 mg/kg (10 mg/ml) of PCr immediately before preparing the IR model>. After 24 h for reperfusion, the neurological function was evaluated and the tissue was sampled to detect expression of XIAP, Smac and caspase-3 positive cells in the ischemic penumbra so as to observe the apoptosis. Results: Compared with group B, neurological deficit scores, numbers of apoptotic cells, expression of Smac,caspase-9 and the numbers of Caspase-3 positive cells were decreased while expression of XIAP were increased in the ischemic penumbra of group C. Conclusions: Phosphocreatine pre-administration may elicit neuroprotective effects in the brain by increasing expression of X-linked inhibitor of apoptosis protein, reducing expression of second mitochondia-derived activator of caspase, and inhibiting the apoptosis in the ischemic penumbra.

Effect of creatine phosphate sodium on bispectral index and recovery quality during the general anaesthesia emergence period in elderly patients: A randomized, double-blind, placebo-controlled trial.

Objective To evaluate the effect of creatine phosphate sodium on bispectral index (BIS) and recovery quality during the general anaesthesia emergence period in elderly patients. Methods This randomized, double-blind, placebo-controlled study enrolled patients undergoing transabdominal cholecystectomy under general anaesthesia. Patients were randomly assigned to receive either creatine phosphate sodium (1.0 g/100 ml 0.9% saline; group P) or 100 ml 0.9% saline (group C) over 30 minutes during surgical incision. The BIS values were recorded at anaesthesia induction (T0), skin incision (T1), cutting the gallbladder (T2), suturing the peritoneum (T3), skin closure (T4), sputum suction (T5), extubation (T6) and 1 min (T7), 5 min (T8), 10 min (T9), and 15 min (T10) after extubation. The anaesthesia duration, operation time, waking time, extubation time, consciousness recovery time, time in the postanaesthesia care unit (PACU), and the Steward recovery scores at T7, T8, T9 and T10 were recorded. Results A total of 120 elderly patients were randomized equally to the two groups. Compared with group C, the BIS values were significantly higher in group P at T5, T6, T7 and T8; and the Steward recovery scores at T7 and T8 were significantly higher in group P. The waking time, extubation time, consciousness recovery time and time in the PACU were significantly shorter in group P compared with group C. Conclusion Creatine phosphate sodium administered during transabdominal cholecystectomy can improve BIS values and recovery following general anaesthesia in elderly patients.

The abnormality of thyroid hormones in patients with type A hepatic encephalopathy.

Abnormality of thyroid hormones in liver diseases is common, but data is lacking in patients with type A hepatic encephalopathy (HE). The present study was aimed to determine whether there was an abnormality in thyroid hormones among patients with type A HE. We measured the levels of thyroid hormones in 36 acute liver failure (ALF) patients with type A HE and in 29 acute liver injury patients (international normalized ratio, INR ≥ 1.5) without encephalopathy as control. The clinical parameters associated with abnormality of thyroid hormones were evaluated. ALF patients with type A HE exhibited decreased TSH levels compared to patients without encephalopathy (0.17 vs 1.08 µIU/mL, P < 0.001). There was no difference in T3 and T4 levels (both total and free) between the two groups. The logistic regression analysis identified type A HE as an independent related factor for the occurrence of low TSH (Odds Ratio = 12.32) in patients with ALF. Correlation analysis showed that there was an inverse correlation between TSH level and the grade of encephalopathy (r = -0.795). Furthermore, patients with low TSH depicted poor survival rate than those with normal TSH level (29.3% vs 44.1%, P = 0.003). Patients with type A HE exhibited subclinical central hypothyroidism, and had significant decreased TSH level, which had inverse correlation with the grade of encephalopathy. The reduced TSH was associated with poor survival rate.