Effectiveness and safety of opioids on breathlessness and exercise endurance in patients with chronic obstructive pulmonary disease: A systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Opioids are recommended to treat advanced refractory dyspnoea despite optimal therapy by the American Thoracic Society clinical practice guidelines, while newly published randomised controlled trials of opioids in chronic obstructive pulmonary disease yield conflicting results. AIM: This study aimed to evaluate the effectiveness and safety of opioids for patients with chronic obstructive pulmonary disease. DESIGN: Systematic review and meta-analysis (PROSPERO CRD42021272556). DATA SOURCES: Databases of PubMed, EMBASE and CENTRAL were searched from inception to 2022 for eligible randomised controlled trials. RESULTS: Twenty-four studies including 975 patients, were included. In cross-over studies, opioids improved breathlessness (standardised mean difference, -0.43; 95% CI, -0.55 to -0.30; I2 = 18%) and exercise endurance (standardised mean difference, 0.22; 95% CI, 0.02-0.41; I2 = 70%). However, opioids failed to improve dyspnoea (standardised mean difference, -0.02; 95% CI, -0.22 to 0.19; I2 = 39%) and exercise endurance (standardised mean difference, 0.00; 95% CI, -0.27 to 0.27; I2 = 0%) in parallel control studies that administered sustained-release opioids for more than 1 week. The opioids used in most crossover studies were short-acting and rarely associated with serious adverse effects. Only minor side effects such as dizziness, nausea, constipation and vomiting were identified for short-acting opioids. CONCLUSIONS: Sustained-release opioids did not improve dyspnoea and exercise endurance. Short-acting opioids appeared to be safe, have potential to lessen dyspnoea and improve exercise endurance, supporting benefit in managing episodes of breathlessness and providing prophylactic treatment for exertional dyspnoea.

Effect evaluation of methylprednisolone plus mitochondrial division inhibitor-1 on spinal cord injury rats.

PURPOSE: To investigate the combination effect of methylprednisolone (MP) and mitochondrial division inhibitor-1 (Mdivi-1) on the neurological function recovery of rat spinal cord injury (SCI) model. METHODS: The weight-drop method was used to establish the rat SCI model; then, rats were randomized into sham group, SCI group, MP group, Mdivi-1 group and MP+Mdivi-1 group. Motor function scores were quantified to evaluate locomotor ability; HE staining was used to assess spinal cord histopathology; tissue water content, oxidative stress, tissue mitochondrial function, neurons apoptosis, and apoptosis-related protein expression were detected. RESULTS: From the third day after SCI, BBB score of the MP+Mdivi-1 group was obviously higher than the other experimental groups (p < 0.05). Compared with the SCI group, tissue water content of the Mdivi-1 group and MP+Mdivi-1 group reduced obviously (p < 0.05), mitochondrial membrane potential (MMP) level and ATP content in the Mdivi-1 group and MP+Mdivi-1 group were both higher (p < 0.05). Meanwhile, three kinds of treatment all reduced apoptosis significantly, while MP plus Mdivi-1 exhibited the best inhibition effect on apoptosis (p < 0.05). The expression levels of Drp1, cytochrome c, and caspase-3 were all upregulated obviously; Mdivi-1 could inhibit Drp1 upregulation induced by SCI; for the upregulation of cytochrome c and caspase-3, the inhibition effect of Mdivi-1 approached MP. When MP combined with Mdivi-1, there was the best inhibition effect. CONCLUSIONS: MP combined with Mdivi-1 may produce better neurological function recovery, through improving functional status of mitochondria and inhibiting lipid peroxidation in damaged tissue of SCI rats, and thus alleviating apoptosis.

Efficacy and cerebral mechanisms of acupuncture for chronic obstructive pulmonary disease: study protocol for a multicenter, randomized controlled neuroimaging trial.

Introduction: Although acupuncture is recommended by chronic obstructive pulmonary disease (COPD) treatment guidelines owing to its effects on dyspnea, the underlying neurobiological mechanisms of these effects remain unclear. This study aims to evaluate the efficacy of acupuncture in patients with stable COPD and explore the possible involvement of specific brain regions. Methods: This is a prospective, multicenter, single-blind, randomized controlled trial. A total of 90 participants will be recruited from three centers and will be randomly assigned in a 1:1 ratio to undergo acupuncture at acupoints on the disease-affected meridian (DAM) or non-acupoints on the non-affected meridian (NAM), in addition to routine pharmacological treatments. All participants will undergo 30 min of acupuncture three times a week for 8 weeks and will be followed up for 12 months. The primary outcome will be the severity of dyspnea, as measured using the Borg Dyspnea Scale and a visual analog scale at rest and after exercise. The secondary outcomes will include the multidimensional profile of dyspnea using Dyspnea-12, the modified Medical Research Council Dyspnea Scale, and the COPD assessment test; quality of life assessments using St George's Respiratory Questionnaire and the Hospital Anxiety and Depression Scale; and additional measurements of exacerbation frequency, pulmonary function, and the 6-min walking distance. Magnetic resonance imaging (MRI) will be performed before and after exercise to explore the potential neurobiological mechanisms of exertional dyspnea. Anxiety and depression will be measured and analyzed for their correlation with the activation of specific brain areas involved in dyspnea. Discussion: This randomized controlled trial aims to use a multidimensional evaluation of the efficacy of acupuncture in relieving dyspnea in patients with COPD in terms of emotion and quality of life and explore the neurobiological mechanisms underlying the effects of acupuncture on dyspnea from an imaging perspective. It is expected to provide strong evidence to support the use of acupuncture in relieving dyspnea in patients with COPD and those with aother diseases involving dyspnea. Additionally, it provides novel insights into the central mechanisms of acupuncture intervention and dyspnea. Trial registration: Chinese Clinical Trial Registry (https://www.chictr.org.cn/): ChiCTR2300071725.

[Progress of researches on anti-inflammatory mechanism of acupuncture underlying amelioration of chronic respiratory diseases].

In recent years, acupuncture has gained great progress in the treatment of chronic respiratory diseases (CRD), and the clinical effect is remarkable, but its underlying mechanisms are relatively complex, with the anti-inflammatory effect being the primary aspect. Based on the literature both at home and abroad, we found that the anti-inflammatory mechanism of acupuncture mainly involves chemokines, kinase-related pathways, helper T cells, epigenetic modification, autophagy, vagal-mediated cholinergic anti-inflammatory pathway, etc. The researches on some anti-inflammatory mechanisms are still in the initial stage, the relationship among various pathways, and the key factors affecting the effect of acupuncture, such as acupoint selection, stimulation intensity and needling depth, etc. warrant further exploration in the future.

[Effect of propofol on the transcription activity of endothelial nitric oxide synthase gene promoter in human umbilic vein endothelial cells induced by lipopolysaccharide].

OBJECTIVE: To observe the effect of propofol on the transcription activity of endothelial nitric oxide synthase (heNOS) gene promoter in human umbilic vein endothelial cells (HUVECs) induced by lipopolysaccharide (LPS). METHODS: heNOS gene promoter sequence (from-1 to -1600 bp) was subcloned into the Bgl II/Hind III sites of the firefly luciferase reporter gene vector, pGL2-Basic, to obtain the recombinant plasmid peNOS-Luc. peNOS-Luc, pGL2-Basic and pCMV-beta were cotransfected into HUVECs, which were treated subsequently with LPS, LPS+propofol and LPS+transforming growth factor beta1 (TGF beta 1), respectively. The relative activities (Luc/beta-gal) were determined in the cell lysates to evaluate the activity of heNOS gene promoter. RESULTS: Double restriction enzyme digestion and sequencing both confirmed successful construction of the recombinant plasmid peNOS-Luc, which could be effectively expressed in HUVECs. Upon LPS stimulation, the luciferase activity was obviously decreased, contrary to the effects of propofol and TGFb1 treatment, and between the latter two agents, TGF beta 1 produced higher transcription activity. CONCLUSION: Propofol can up-regulate the activity of heNOS gene promoter in HUVECs and affect the nitrogen monoxide production and release at the transcriptional level, which is probably one of mechanisms for propofol to ameliorate LPS-induced inflammatory reaction.