To reduce pain after total hip replacement (THR), researchers are interested in drug-free interventions. However, there is still a lack of consensus on their prevention efficacy. We performed a meta-analysis to evaluate the use of nonpharmaceutical interventions for postoperative pain management after THR. We searched the Cochrane Library, MEDLINE, EMBASE, Web of Science, PEDRO, and ClinicalTrials.gov databases for articles published between and 1991 and 2020. The main outcome measures were postoperative pain, opioid consumption, and quality of life (QoL). In total, 1,942 patients were studied. We found moderate evidence indicating postoperative pain relief measured by the Western Ontario and McMaster Universities Arthritis Index Scale, with mean differences (MDs) of -0.28 (95% confidence interval [CI], -0.49 to -0.07; P=0.01; I2 =0%) within three months, -0.19 (95% CI, -0.40 to 0.02; P=0.07; I2 =0%) between 3-6 months, and -0.13 (95% CI, -0.35 to 0.08; P=0.21; I2 =0%) between 6-12 months. Additionally, we found that acupuncture therapy could reduce opioid analgesic consumption (MD, -0.98; 95% CI, -1.18 to -0.79; fentanyl [mg/h]; P<0.01; I2 =72.2%) and significantly improve pain relief with an MD of 0.90 (95% CI, 0.47 to 1.33; P<0.01; I2 =0%) measured using the visual analog scale. Electrotherapy slightly improved perceived pain with an MD of 0.22 (95% CI, -0.27 to 0.70; P=0.37; I2 =0%). Moreover, moderate evidence has shown that preoperative exercises improve QoL. This meta-analysis suggested that continuous passive motion did not improve pain or QoL. Postoperative exercise was associated with pain relief and improved QoL. Acupuncture therapy after THR has been shown to reduce opioid analgesic consumption.
Background Bioinformatics analysis was performed on gene expression profile microarray data to identify the key genes activated through the TNF-α/TNFR1 signaling pathway in intervertebral disc degeneration (IDD). The common differentially expressed genes (co-DEGs) were calculated in nucleus pulposus (NP) cells and annulus fibrosus (AF) cells under TNF-α treatment or TNFR1 knockdown, which reveals the potential mechanism of TNF-α involvement in IDD and may provide new therapeutic targets for IDD.Methods Differentially expressed genes (DEGs) in TNF-α-treated or TNFR1-knockdown NP cells and AF cells were identified. Further analysis of the gene ontology (GO), signaling pathways and interaction networks of the DEGs or co-DEGs were conducted using the Database for Annotation, Visualization and Integrated Discovery, STRING Database, and Cytoscape software. The relationship between genes and musculoskeletal diseases, including IDD, was assessed with the Comparative Toxicogenomics Database. The predicted microRNAs corresponding to the co-DEGs were also identified by microRNA Data Integration Portal.Results In NP cells, the DEGs (|log2FoldChange|>2, adj.P < 0.01) were identified including 48 DEGs by TNF-α treatment and 74 DEGs by TNFR1 knockdown; in AF cells, correspondingly, 105 DEGs were identified. The co-DEGs between NP cells and AF cells were calculated including CXCL8, ICAM1, BIRC3, RELB, NFKBIA, and TNFAIP3. They may be the hub genes that were significantly associated with both NP cells and AF cells through the TNF-α/TNFR1 signaling pathway. The co-DEGs and corresponding predicted miRNAs may be potential therapeutic targets for IDD.Conclusions CXCL8, ICAM1, BIRC3, RELB, NFKBIA, and TNFAIP3 may have a synergistic effect on TNF-α-induced IDD development.Abbreviations: IDD: Intervertebral disc degeneration; NP: Nucleus pulposus; AF: Annulus fibrosus; co-DEG: Common differentially expressed gene; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; PPI: Protein-protein interaction.
Abstract An imbalance between matrix synthesis and degradation is the hallmark of intervertebral disc degeneration while inflammatory cytokines contribute to the imbalance. Bromodomain and extra‐terminal domain (BET) family is associated with the pathogenesis of inflammation, and inhibition of BRD4, a vital member of BET family, plays an anti‐inflammatory role in many diseases. However, it remains elusive whether BRD4 plays a similar role in nucleus pulposus (NP) cells and participates in the pathogenesis of intervertebral disc degeneration. The present study aims to observe whether BRD4 inhibition regulates matrix metabolism by controlling autophagy and NLRP3 inflammasome activity. Besides, the relationship was investigated among nuclear factor κB (NF‐κB) signaling, autophagy and NLRP3 inflammasome in NP cells. Here, real‐time polymerase chain reaction, western blot analysis and adenoviral GFP‐LC3 vector transduction in vitro were used, and it was revealed that BRD4 inhibition alleviated the matrix degradation and increased autophagy in the presence or absence of tumor necrosis factor α. Moreover, p65 knockdown or treatment with JQ1 and Bay11‐7082 demonstrated that BRD4 inhibition attenuated NLRP3 inflammasome activity through NF‐κB signaling, while autophagy inhibition by bafilomycin A1 promoted matrix degradation and NLRP3 inflammasome activity in NP cells. In addition, analysis of BRD4 messenger RNA expression in human NP tissues further verified the destructive function of BRD4. Simply, BRD4 inhibition alleviates matrix degradation by enhancing autophagy and suppressing NLRP3 inflammasome activity through NF‐κB signaling in NP cells.
Abstract Intestinal ischemia-reperfusion (II/R) injury is an urgent clinical disease with high incidence and mortality, and impaired intestinal barrier function caused by excessive apoptosis of intestinal cells is an important cause of its serious consequences. Tripartite motif-containing protein 65 (TRIM65) is an E3 ubiquitin ligase that is recently reported to suppress the inflammatory response and apoptosis. However, the biological function and regulation of TRIM65 in II/R injury are totally unknown. We found that TRIM65 was significantly decreased in hypoxia-reoxygenation (H/R) induced intestinal epithelial cells and II/R-induced intestine tissue. TRIM65 knockout mice markedly aggravated intestinal apoptosis and II/R injury. To explore the molecular mechanism of TRIM65 in exacerbating II/R-induced intestinal apoptosis and damage, thymocyte selection-associated high mobility group box factor 4 (TOX4) was screened out as a novel substrate of TRIM65 using the yeast two-hybrid system. TRIM65 binds directly to the N-terminal of TOX4 through its coiled-coil and SPRY structural domains. Immunofluorescence confocal microscopy showed that they can co-localize both in the cytoplasm and nucleus. Furthermore, TRIM65 mediated the K48 ubiquitination and degradation of TOX4 depending on its E3 ubiquitin ligase activity. In addition, TRIM65 inhibits H/R-induced intestinal epithelial apoptosis via TOX4. In summary, our results indicated that TRIM65 promotes ubiquitination and degradation of TOX4 to inhibit apoptosis in II/R. These findings provide a promising target for the clinical treatment of II/R injury.
TCF7L2, a key transcription factor in the canonical Wnt pathway, plays a vital role in the matrix degradation of chondrocytes. However, it is unknown whether TCF7L2 is important in the matrix metabolism of inner gel-like nucleus pulposus (NP) cells; thus, the aim of this study was to explore the effect and mechanism of TCF7L2 in this process.Western blotting and immunofluorescence analyses were used to observe TCF7L2 expression in rat and human NP tissues. Real-time PCR and western blotting were performed to detect the expression of TCF7L2 stimulated by inflammatory cytokines. Dual luciferase reporter assay, real-time PCR, western blotting and knockdown experiments were performed to demonstrate the role of NF-κB signaling in matrix regulation by TCF7L2 and the regulation of TCF7L2 by miR-155 in intervertebral disc degeneration.TCF7L2 is present in rat and human NP tissues and is expressed in the nucleus of NP cells. TCF7L2 is refractory to stimulation of rat and human NP cells with the inflammatory cytokines TNF-α and IL-1β, in contrast to the results in other cell types. Loss-of-function experiments using TCF7L2 siRNA or lentiviral shTCF7L2 showed that TCF7L2 knockdown suppresses matrix degradation through p65/NF-κB signaling in the absence and presence of TNF-α. In addition, TCF7L2 expression is repressed by miR-155 overexpression and promoted by miR-155 inhibition.Overall, these results demonstrate that the suppression of TCF7L2, which is modulated by miR-155, inhibits matrix degradation through p65/NF-κB signaling. TCF7L2 suppression may have therapeutic potential in intervertebral disc degeneration.
Objective. To investigate the clinical efficacy of this combined treatment for chronic pelvic pain syndrome (CPPS) by meta-analysis. Methods. Relevant articles were retrieved from PubMed, CNKI, Wanfang Data, Web of Science, and Embase, including randomized controlled trials on acupuncture combined with rehabilitation for CPPS in females. Results. A total of 224 articles were retrieved in this study, and 14 studies were finally identified for inclusion. Among them, the treatment group was treated with acupuncture combined with pelvic floor rehabilitation therapy, while the control group was treated with acupuncture or pelvic floor rehabilitation therapy. Meta-analysis showed that the treatment effective rate in the treatment group was significantly higher than that in the control group (OR = 6.54; 95% CI: 4.20, 10.21; P < 0.05). After treatment, compared with the control group, the treatment group showed lower incidences of adverse reactions (OR = 0.16; 95% CI: 0.09, 0.27; P < 0.05), bladder prolapse (OR = 0.36; 95% CI: 0.18, 0.73; P < 0.05), cervical prolapse (OR = 0.22; 95% CI: 0.10, 0.49; P < 0.05), and pelvic peritoneal hernia (OR = 0.14; 95% CI: 0.05, 0.38; P < 0.05); in addition, the treatment group was also associated with lower pain score (SMD = −4.05; 95% CI: −6.75, −1.34; P < 0.05) and pelvic dysfunction score (SMD = -4.35; 95% CI: -5.37, -3.34; P < 0.05). Conclusion. Acupuncture combined with rehabilitation is effective for CPPS in females, which can significantly reduce the pain intensity and improve pelvic dysfunction of patients.
The inhibitory effect of nanoscale silicate platelets modified with different surfactants, i.e., NSS1450 and NSS3150 was evaluated for spore germination and mycelial growth of azoxystrobin-resistant (AR) and -sensitive (AS) Botrytis cinerea isolates from strawberry. The treatments with NSS1450 at the concentration of more than 50 mg/L significantly reduced spore germination by 99.2-100.0% for AR isolates and by 100.0% for AS isolates. In contrast, NSS3150 failed to show an inhibition for the spore germination of AR B. cinerea isolates. In another test, NSS1450 at concentrations higher than 500 mg/L could reduce mycelial growth by 60.2-100.0% and 93.8- 100.0% for AR and AS isolates, respectively, while NSS3150 showed similar inhibition on the spore germination. Further, NSS1450 at the concentrations between 500 to 1000 mg/L and accompanied with a fungicide, azoxystrobin, demonstrated high inhibitory rate 93.8 to 100.0% inhibition) in AR and AS isolates of B. cinerea. Under scanning electron microscope, the NSS1450 at the concentration of 1000 mg/L affected the morphologies of spores and mycelia in shrinking. The disease severity on strawberry leaves was 8.3% after 13 days incubation when treated with NSS1450 at 24 h after the pathogen inoculation. Moreover, spraying the mixture solution of 100 mg/L NSS1450 and 100 mg a.i./L azoxystrobin at 24 h after or before pathogen inoculation showed significantly efficacy compared with inoculation pathogen only. The results indicated that the silicate nanoplatelets after modification by a proper surfactant or NSS1450 had the potentials for treating gray mold disease although further studies are still needed under greenhouse and field conditions.
Background Many studies have investigated the efficacy of acupuncture in treating depression, but the mechanism of acupuncture for depression is still controversial and there is a lack of meta-analysis of mechanisms. Consequently, we investigated acupuncture’s efficacy and mechanism of depression. Methods We searched the Cochrane Library, PubMed, EMBASE, Web of Science. The SYRCLE Risk of Bias Tool was used to assess bias risk. Meta-analysis was performed using Stata 15.0 for indicators of depression mechanisms, body weight and behavioral tests. Results A total of 22 studies with 497 animals with depressive-like behaviors were included. Meta-analysis showed that acupuncture significantly increased BDNF [SMD = 2.40, 95% CI (1.33, 3.46); I 2 = 86.6%], 5-HT [SMD = 2.28, 95% CI (1.08, 3.47); I 2 = 87.7%] compared to the control group ( p < 0.05), and significantly reduced IL-1β [SMD = −2.33, 95% CI (−3.43, −1.23); I2 = 69.6%], CORT [SMD = −2.81, 95% CI (−4.74, −0.87); I 2 = 86.8%] ( p < 0.05). Acupuncture improved body weight [SMD = 1.35, 95% CI (0.58, 2.11); I 2 = 84.5%], forced swimming test [SMD = −1.89, 95% CI (−2.55, −1.24); I 2 = 76.3%], open field test (crossing number [SMD = 3.08, 95% CI (1.98, 4.17); I 2 = 86.7%], rearing number [SMD = 2.53, 95% CI (1.49, 3.57); I 2 = 87.0%]) ( p < 0.05) compared to the control group. Conclusion Acupuncture may treat animals of depressive-like behaviors by regulating neurotrophic factors, neurotransmitters, inflammatory cytokines, neuroendocrine system. Systematic review registration https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023403318 , identifier (CRD42023403318).
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