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OBJECTIVE@#To evaluate the effect of curcumin on renal mitochondrial oxidative stress, nuclear factor-κB/NOD-like receptor protein 3 (NF-κB/NLRP3) inflammatory body signaling pathway and tissue cell injury in rats with acute respiratory distress syndrome (ARDS).@*METHODS@#A total of 24 specific pathogen free (SPF)-grade healthy male Sprague-Dawley (SD) rats were randomly divided into control group, ARDS model group, and low-dose and high-dose curcumin groups, with 6 rats in each group. The ARDS rat model was reproduced by intratracheal administration of lipopolysaccharide (LPS) at 4 mg/kg via aerosol inhalation. The control group was given 2 mL/kg of normal saline. The low-dose and high-dose curcumin groups were administered 100 mg/kg or 200 mg/kg curcumin by gavage 24 hours after model reproduction, once a day. The control group and ARDS model group were given an equivalent amount of normal saline. After 7 days, blood samples were collected from the inferior vena cava, and the levels of neutrophil gelatinase-associated lipocalin (NGAL) in serum were determined by enzyme-linked immunosorbent assay (ELISA). The rats were sacrificed, and kidney tissues were collected. Reactive oxygen species (ROS) levels were determined by ELISA, superoxide dismutase (SOD) activity was detected using the xanthine oxidase method, and malondialdehyde (MDA) levels were determined by colorimetric method. The protein expressions of hypoxia-inducible factor-1α (HIF-1α), caspase-3, NF-κB p65, and Toll-like receptor 4 (TLR4) were detected by Western blotting. The mRNA expressions of HIF-1α, NLRP3, and interleukin-1β (IL-1β) were detected by reverse transcription-polymerase chain reaction (RT-PCR). Renal cell apoptosis was detected by TdT-mediated dUTP nick end labeling (TUNEL). The morphological changes in renal tubular epithelial cells and mitochondria were observed under a transmission electron microscope.@*RESULTS@#Compared with the control group, the ARDS model group exhibited kidney oxidative stress and inflammatory response, significantly elevated serum levels of kidney injury biomarker NGAL, activated NF-κB/NLRP3 inflammasome signaling pathway, increased kidney tissue cell apoptosis rate, and renal tubular epithelial cell damage and mitochondrial integrity destruction under transmission electron microscopy, indicating successful induction of kidney injury. Following curcumin intervention, the injury to renal tubular epithelial cells and mitochondria in the rats was significantly mitigated, along with a noticeable reduction in oxidative stress, inhibition of the NF-κB/NLRP3 inflammasome signaling pathway, and a significant decrease in kidney tissue cell apoptosis rate, demonstrating a certain dose-dependency. Compared with the ARDS model group, the high-dose curcumin group exhibited significantly reduced serum NGAL levels and kidney tissue MDA and ROS levels [NGAL (μg/L): 13.8±1.7 vs. 29.6±2.7, MDA (nmol/g): 115±18 vs. 300±47, ROS (kU/L): 75±19 vs. 260±15, all P < 0.05], significantly down-regulated protein expressions of HIF-1α, caspase-3, NF-κB p65, and TLR4 in the kidney tissue [HIF-1α protein (HIF-1α/β-actin): 0.515±0.064 vs. 0.888±0.055, caspase-3 protein (caspase-3/β-actin): 0.549±0.105 vs. 0.958±0.054, NF-κB p65 protein (NF-κB p65/β-actin): 0.428±0.166 vs. 0.900±0.059, TLR4 protein (TLR4/β-actin): 0.683±0.048 vs. 1.093±0.097, all P < 0.05], and significantly down-regulated mRNA expressions of HIF-1α, NLRP3, and IL-1β [HIF-1α mRNA (2-ΔΔCt): 2.90±0.39 vs. 9.49±1.87, NLRP3 mRNA (2-ΔΔCt): 2.07±0.21 vs. 6.13±1.32, IL-1β mRNA (2-ΔΔCt): 1.43±0.24 vs. 3.95±0.51, all P < 0.05], and significantly decreased kidney tissue cell apoptosis rate [(4.36±0.92)% vs. (27.75±8.31)%, P < 0.05], and significantly increased SOD activity (kU/g: 648±34 vs. 430±47, P < 0.05).@*CONCLUSIONS@#Curcumin can alleviate kidney injury in ARDS rats, and its mechanism may be related to the increasing in SOD activity, reduction of oxidative stress, and inhibition of the activation of the NF-κB/NLRP3 inflammasome signaling pathway.
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Masculino , Ratos , Animais , Ratos Sprague-Dawley , NF-kappa B , Actinas , Caspase 3 , Curcumina , Lipocalina-2 , Receptor 4 Toll-Like , Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Espécies Reativas de Oxigênio , Solução Salina , Rim , Superóxido DismutaseRESUMO
Vascular cognitive impairment (VCI) is a clinical syndrome with impairment of at least one cognitive domain caused by vascular risk factors or cerebrovascular diseases, and its pathogenesis is not completely clear so far. Microglia are innate immune cells in the brain. They participate in many processes such as neuroinflammation, synaptic pruning, myelin regeneration, neurogenesis and connection. They are associated with the occurrence and development of various neurological diseases such as cerebral infarction, Alzheimer's disease, Parkinson's disease, and autism. Recent studies have shown that microglia play an important role in the development of VCI. This article reviews the role of microglia in VCI.
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BACKGROUND:At present, dexamethasone has been widely used in the perioperative period of major surgery in the orthopedics for reducing postoperative pain and nausea and vomiting, but the study on the application of methylprednisolone to reducing postoperative nausea and vomiting and pain after unilateral total knee arthroplasty is rarely reported.OBJECTIVE:To evaluate the effects and safety assessment of the application of methylprednisolone on postoperative nausea and vomiting and pain after unilateral total knee arthroplasty. METHODS:A total of 86 patients undergoing unilateral total knee arthroplasty were randomly assigned to two groups. Patients in the methylprednisolone group were given methylprednisolone 40 mg in intravenous drip within 24 hours during and after replacement. Patients in the control group were given an equal volume of saline in intravenous drip at the same time. The incidence of postoperative nausea and vomiting was observed and recorded at 0-6 hours, 6-24 hours, 24-48 hours, and 48-72 hours after surgery, as wel as the total incidence was recorded in both groups. Pain visual analogue scale (VAS) score at 6, 24, 48 and 72 hours after replacement, and knee joint scoring system (KSS) score at 3 days after replacement were recorded. C-reactive protein and fasting blood glucose were determined. The occurrence of adverse reactions postoperatively was recorded in 6-month fol ow-up in both groups. RESULTS AND CONCLUSION:(1) The total incidence rate of postoperative nausea and vomiting during 0-72 hours after surgery, and incidence rates of nausea and vomiting at 6 and 24 hours were significantly lower in the methylprednisolone group than in the control group (P0.05). (5) The surgical incision was found to heal in 3-month fol ow-up and no postoperative infection occurred in both groups. (6) Results show that methylprednisolone can obviously reduce postoperative nausea and vomiting and pain in unilateral total knee arthroplasty, and did not increase the incidence of postoperative infection.
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Objective To evaluate the role and mechanism of ifenprodil, which is the selective antagonist of N-methyl-D-aspartic acid subtype receptor NR2B, in soflurane-induced cognitive dysfunction in neonatal rats.Methods Twenty-eight 7-day-old Sprague Dawley rats, weighing 15-18 g, were randomly divided into 4 groups (n=7 each): control group (group C), ifenprodil group (group I), sevoflurane group (group S) and ifenprodil+sevoflurane group (group IS).Normal saline 0.2 ml was injected intraperitoneally in group C.Specific NR2B receptor antagonist ifenprodil 5 mg/kg was injected intraperitoneally at the corresponding time points in group I.Normal saline 0.2 ml was injected intraperitoneally and 2.0% sevoflurane was inhaled for 4 h in group S.Ifenprodil 5 mg/kg was injected intraperitoneally 2 h before sevoflurance inhalation, and 2.0% sevoflurance was inhaled for 4 h in group IS.The rats were then sacrificed 3 weeks after administration, their brains were immediately removed and hippocampal slices were prepared for electrophyisological experiments.The value of population spike amplitude (PSA) and long-term potentiation (LTP) were measured every 10 minutes.Induced LTP was recorded.Results Compared with group C, the values of PSA and rates of induced LTP were significantly decreased in group S (P＜0.01).The values of PSA and rates of induced LTP were significantly increased in group IS than those in group S (P＜0.01).Conclusion NR2B receptor is involved in sevoflurance-induced cognitive dysfunction in the neonatal rats.Pretreatment with ifenprodil 5.0 mg/kg can improve the neurotoxicity and protect the brain.
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Objective To investigate the efficacy of high frequency jet ventilation via the nasopha?ryngeal catheter in assissting ventilation in patients with obstructive sleep apnea hypopnea syndrome ( OS?AHS) undergoing gastroscopy. Methods Eighty patients with OSAHS of both sexes, aged 40-64 yr, weighing 65-99 kg, of American Society of Anesthesiologists physical status Ⅰ or Ⅱ, with an apnea?hy?popnea index 20-40 events∕h, scheduled for elective painless gastroscopy, were divided into control group and test group using a random number table, with 40 patients in each group. In control group, a nasopha?ryngeal catheter 6.0-7.0 mm in internal diameter was inserted, and oxygen was inhaled at 4 L∕min through the catheter. In test group, a nasopharyngeal catheter 4.0 mm in internal diameter was inserted, and a high frequency jet ventilator was connected ( inspiratory∕expiratory ratio 1. 0 ∶ 1. 5, frequency 150 bpm, peak pressure 0.4 kPa, tidal volume 180 ml) . Anesthesia was maintained with propofol in both groups. The oc?currence of hypoxemia during ventilation, and peak value of partial pressure of end?tidal CO2 before induc?tion of anesthesia and during ventilation, and occurrence of chin lift, mask ventilation, and epistaxis after insertion of the catheter during operation were recorded. Results Compared with control group, the inci?dence of hypoxemia, peak value of partial pressure of end?tidal CO2 during ventilation, and incidence of chin lift, mask ventilation and epistaxis during operation were significantly decreased in test group ( P<0.05) . Conclusion High frequency jet ventilation via the nasopharyngeal catheter can be safely and effec?tively used to assisst ventilation in patients with OSAHS undergoing gastroscopy.
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Objective To evaluate the role of gamma-aminobutyric acid A (GABAA) receptor in isoflurane-induced cognitive dysfunction in neonatal rats.Methods Twenty-eight 7-day-old Sprague Dawley rats,weighing 16-18 g,were randomly divided into 4 groups (n =7 each):control group (group Con),securinine group (group See),isoflurane group (group Iso) and securinine + isoflurane group (group Sec + Iso).Normal saline 0.2 ml was injected intraperitoneally in group Con.Specific GABAA receptor antagonist securinine 30 mg/kg was injected intraperitoneally at the corresponding time points in group Sec.Normal saline 0.2 ml was injected intraperitoneally and 1.4％ isoflurane was inhaled for 6 h in group Iso.Securinine 30 mg/kg was injected intraperitoneally at 30 min before isoflurane inhalation and 3 h of inhalation,and 1.4％ isoflurane was inhaled for 6 h in group Sec + Iso.The rats were then sacrificed at 3 weeks after administration,their brains were immediately removed and hippocampal slices were prepared for electrophysiological experiments.The value of population spike amplitude (PSA) and long-term potentiation (LTP) were measured every 5 min.The successful LTP induction was recorded.Results Compared with group Con,the values of PSA and rates of successful LTP induction were significantly decreased in group Iso (P ＜ 0.01),and no significant change was found in the parameters mentioned above in groups Sec and Sec + Iso (P ＞ 0.05).The values of PSA and rates of successful LTP induction were significantly higher in group Sec + Iso than in group Iso (P ＜ 0.01).Conclusion GABAA receptor is involved in isoflurane-induced cognitive dysfunction in the neonatal rats.
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Objective To investigate the possibility, effect and safety of intracoronary autologous moronuclear bone marrow cell (MBMC) transplantation in patients with ischemia heart failure (IHF). Methods 41 patients with IHF were enrolled in this prospective nonrandomized study. 14 patients were transplanted with autologous MBMC via a balloon catheter placed into the infarct-related artery during balloon dilatation by highpressure infusion, which was performed 6-8 times for 2 minutes each. 13 patients were transplanted via selective the infarct-related arteries by highpressure infusion. Results There were no major periprocedural complications. Two patients had limited premature ventricular contractions during cell infusion forseveral seconds. Two patients felt cold after 15-30 minutes infusing cell and got better several minutes later. There were no new onset of arrhythmias found on 48 h ECG monitoring. After 3 months of follow up, the symptoms and cardiac function were significantly improved in the transplantation group. FDG-PET analysis revealed a significant increase in myocardial metabolism (23.94?7.28)% (P=0.015). Plasma BNP lever decreased significatly at 3 days and 7 days after transplantation than before transplantation (P