[Curcumin alleviates nuclear factor-κB/NOD-like receptor protein 3 mediated renal injury caused by acute respiratory distress syndrome through reducing mitochondrial oxidative stress].

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-1ß (IL-1ß) 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/ß-actin): 0.515±0.064 vs. 0.888±0.055, caspase-3 protein (caspase-3/ß-actin): 0.549±0.105 vs. 0.958±0.054, NF-κB p65 protein (NF-κB p65/ß-actin): 0.428±0.166 vs. 0.900±0.059, TLR4 protein (TLR4/ß-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-1ß [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-1ß 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.

Efficacy of Internal Heat Acupuncture Combined with High-Voltage Long-Duration Pulsed Radiofrequency on Subacute Postherpetic Neuralgia: A Retrospective Study.

Objectives: This study aims at investigating the internal heat acupuncture (IHA) combined with the high-voltage long-duration pulsed radiofrequency (PRF) therapeutic effect on subacute postherpetic neuralgia (PHN). Methods: This retrospective study comprised 81 cases with PHN. They were divided into three groups: IHA combined with the high-voltage long-duration PRF group (IHA-PRF), intradermal injection combined with the high-voltage long-duration PRF group (II-PRF), and the high-voltage long-duration PRF group. The pain numerical rating score (NRS), IL-6, Gal-3, and blood glucose levels were recorded before and after treatment. Results: Compared with before treatment, NRS scores of the three groups were all decreased at each time point. NRS scores of the IHA-PRF group patients decreased significantly in comparison to the PRF group at 1, 4, 8, and 12 weeks following treatment, while group II-PRF only decreased significantly at one week following treatment. Compared with groups II-PRF and PRF, respectively, IL-6 and Gal-3 levels in plasma of patients in group IHA-PRF were significantly decreased at 4 and 12 weeks after treatment. The effective rate of group IHA-PRF was 88.9%, which was considerably more than the other groups, II-PRF (63.0%) and PRF (63.0%). Compared with group II-PRF, patients' blood glucose levels in IHA-PRF and PRF groups significantly decreased three days and one week after treatment. Conclusion: Internal heat acupuncture combined with high-voltage long-duration pulsed radiofrequency has a satisfactory therapeutic effect on subacute PHN and has no obvious adverse reactions, which is especially suitable for patients with poor blood glucose control.

CT-guided Chemical Lumbar Sympathectomy in the Treatment of Cold Hypersensitivity in the Hands and Feet.

BACKGROUND: Cold hypersensitivity in the hands and feet is a common clinical symptom in Asian women. Currently, treatment of cold hypersensitivity in the hands and feet is still limited to traditional Chinese medicine, mainly herbal medicine. However, many patients with cold hypersensitivity in the hands and feet in China are not satisfied with the therapeutic effect of herbal medicine, and took medication for a longer time. Chemical lumbar sympathectomy is widely used in the treatment of plantar hyperhidrosis, diabetic foot, recalcitrant erythromelalgia, and other diseases. OBJECTIVES: This study was conducted to evaluate the short-term as well as long-term efficacy, complications, and patient satisfaction of chemical lumbar sympathectomy during treatment cold hypersensitivity in the hands and feet. STUDY DESIGN: A retrospective, observational study. SETTING: Department of Anesthesiology and Pain Medicine, Jiaxing, China. METHODS: A retrospective study of 72 patients with cold hypersensitivity in the hands and feet who received chemical lumbar sympathectomy treatment in our hospital from January 2015 to October 2018 was conducted. The heart rate, non-invasive blood pressure, oxygen saturation, visual analog scale, perfusion index, and plantar temperature were monitored and recorded in before treatment (T1) and after treatment (T2) groups. The patients were followed up on day 1, at week 1, 1 month, 3 months, 6 months, one year, and 2 years after operation for satisfaction, complications, and recurrence. RESULTS: There were no significant differences in heart rate, non-invasive blood pressure, and oxygen saturation between T1 and T2 groups (P > 0.05). Perfusion index and plantar temperature in T2 group were remarkably higher than T1 group, and the difference was statistically significant (P < 0.01). The visual analog scale score of the T2 group was significantly reduced (P < 0.01). Of all the patients who underwent chemical lumbar sympathectomy, the postoperative therapeutic effect was effective in 63 cases (87.5%) and ineffective in 9 cases (12.5%). Among the effective patients, the postoperative curative effect was shown to be excellent in 47 cases and improved in 16 cases. According to the follow-up results at day 1, 1 week, 1 month, 3 months, 6 months, 1 year, and 2 years after operation, the satisfaction rate was 87.5%, 87.5%, 81.9%, 61.1%, 52.7%, 41.6%, and 34.7%, respectively. There were no serious complications observed and 23 patients relapsed after two years. Multivariate logistic regression analysis results showed that the effect of visual analog scale (OR = 7.312, 95% CI: 1.598 - 33.646, P = 0.011) and plantar temperature (OR = 0.470, 95% CI: 0.288 - 0.766, P = 0.002) on therapeutic effect showed has statistical significance; the effect of gender (OR = 0.654, 95% CI: 0.134 - 3.181, P = 0.599), age (OR = 0.975, 95% CI: 0.916 - 1.039, P = 0.441), perfusion index (OR = 0.710, 95% CI: 0.367 - 1.375, P = 0.310), and disease course (OR = 1.019, 95% CI: 0.997 - 1.042, P = 0.088) on therapeutic effect showed no statistical significance. The effect of gender (OR = 0.451, 95% CI 0.131 - 1.554, P = 0.207), age (OR = 0.961, 95% CI 0.912 - 1.013, P = 0.141), and course of disease (OR = 1.006, 95% CI 0.997 - 1.015, P = 0.203) on postoperative recurrence showed no statistical significance. LIMITATIONS: The nonrandomized, single-center, small sample size, retrospective design is a major limitation of this study. CONCLUSIONS: Chemical lumbar sympathectomy is a valid treatment option for cold hypersensitivity in hands and feet, and computed tomography-guided percutaneous puncture chemical lumbar sympathectomy has the advantages of high success rate, less invasion, less complications, and repeatablity.

Enhanced NMDA receptor NR1 phosphorylation and neuronal activity in the arcuate nucleus of hypothalamus following peripheral inflammation.

UNLABELLED: AbstractAim:To investigate the role of glutamate and N-methyl-D-aspartate (NMDA) receptors in central sensitization following peripheral inflammation in the arcuate nucleus (ARC) of the mediobasal hypothalamus. METHODS: Mediobasal hypothalamic slices were prepared from rats undergoing peripheral inflammation, which was induced by a unilateral injection of complete Freund's adjuvant (CFA) into hind paw. Neuronal activation levels in the ARC were monitored by recording extracellular unit discharges. The NMDA receptor NR1 subunit (NR1) was measured using Western blot analysis. RESULTS: Enhanced NR1 phosphorylation was observed in the ARC of CFA-inflamed rats. Compared with the control rats, the firing rate of spontaneous discharges in ARC neurons of inflamed rats was significantly higher, and it was significantly reduced both by an NMDA receptor antagonist (MK-801, 300 µmol/L) and by a non-NMDA receptor antagonist (CNQX, 30 µmol/L). Application of exogenous glutamate (200 µmol/L) or NMDA (25 µmol/L) resulted in increased neuronal discharges for ARC neurons, which was enhanced to a greater extent in inflamed rats than in control rats. CONCLUSION: Glutamate receptor activation in the hypothalamic ARC plays a crucial role in central sensitization associated with peripheral inflammation.