Accepted

Osteoarthritis (OA) reduces the quality of life as a result of the pain caused by continuous joint destruction. Inactivated (LA-1) ameliorated osteoarthritis and protected cartilage by modulating inflammation. In this study, we evaluated the mechanism by which live LA-1 ameliorated OA. To investigate the effect of live LA-1 on OA progression, we administered LA-1 into monosodium iodoacetate (MIA)-induced OA animals. The pain threshold, cartilage damage, and inflammation of the joint synovial membrane were improved by live LA-1. Furthermore, the analysis of intestinal tissues and feces in the disease model has been shown to affect the systems of the intestinal system and improve the microbiome environment. Interestingly, inflammation of the intestinal tissue was reduced, and the intestinal microbiome was altered by live LA-1. Live LA-1 administration led to an increase in the level of which is a short-chain fatty acid (SCFA) butyrate-producing bacteria. The daily supply of butyrate, a bacterial SCFA, showed a tendency to decrease necroptosis, a type of abnormal cell death, by inducing autophagy and reversing impaired autophagy by the inflammatory environment. These results suggest that OA is modulated by changes in the gut microbiome, suggesting that activation of autophagy can reduce aberrant cell death. In summary, live LA-1 or butyrate ameliorates OA progression by modulating the gut environment and autophagic flux. Our findings suggest the regulation of the gut microenvironment as a therapeutic target for OA.

To estimate the prevalence of chronic back pain (CBP) and its associated factors.

Endometriosis (EMS) is a chronic disease that can cause dysmenorrhea, chronic pelvic pain, and infertility, among other symptoms. EMS diagnosis is often delayed compared to other chronic diseases, and there are currently no accurate, easily accessible, and non-invasive diagnostic tools. Therefore, it is important to elucidate the mechanism of EMS and explore potential biomarkers and diagnostic tools for its accurate diagnosis and treatment. In the present study, we comprehensively analyzed the differential expression, immune infiltration, and interactions of EMS-related genes in three datasets. Our results identified 332 differentially expressed genes (DEGs) associated with EMS. Gene ontology analysis showed that these changes mainly focused on the positive regulation of endometrial cell proliferation, cell metabolism, and extracellular space, and EMS involved the integrin, complement activation, folic acid metabolism, interleukin, and lipid signaling pathways. The LASSO regression model was established using immune DEGs with an area under the curve of 0.783 for the internal dataset and 0.656 for the external dataset. Five genes with diagnostic value, , , , , and , were screened from M1 and M2 macrophages, activated mast cells, neutrophils, natural killer cells, follicular T helper cells, CD8, and CD4 cells. A protein-protein interaction network based on the immune DEGs was constructed, and ten hub genes with the highest scores were identified. Our results may provide a framework for the development of pathological molecular networks in EMS.

Fibromyalgia is a chronic pain syndrome characterized by dysfunctional processing of nociceptive stimulation. Neuroimaging studies have pointed out that pain-related network functioning seems to be altered in these patients. It is thought that this clinical symptomatology may be maintained or even strengthened because of an enhanced expectancy for painful stimuli or its forthcoming appearance. However, neural electrophysiological correlates associated with such attentional mechanisms have been scarcely explored. In the current study, expectancy processes of upcoming laser stimulation (painful and non-painful) and its further processing were explored by event-related potentials (ERPs). Nineteen fibromyalgia patients and twenty healthy control volunteers took part in the experiment. Behavioral measures (reaction times and subjective pain perception) were also collected. We manipulated the pain/no pain expectancy through an S1-S2 paradigm (cue-target). S1 (image: triangle or square) predicted the S2 appearance (laser stimulation: warmth or pinprick sensation). Laser stimuli were delivered using a CO laser device. Temporal and spatial principal component analyses were employed to define and quantify the ERP component reliability. Statistical analyses revealed the existence of an abnormal pattern of pain expectancy in patients with fibromyalgia. Specifically, our results showed attenuated amplitudes at posterior lCNV component in anticipation of painful stimulation that was not found in healthy participants. In contrast, although larger P2 amplitudes to painful compared to innocuous events were shown, patients did not show any amplitude change in this laser-evoked response as a function of pain predictive cues (as occurred in the healthy control group). Additionally, analyses of the subjective perception of pain and reaction time indicated that laser stimuli preceded by pain cues were rated as more painful than those signaling non-pain expectancy and were associated with faster responses. Differences between groups were not found. The present findings suggest the presence of dysfunction in pain expectation mechanisms in fibromyalgia that eventually may make it difficult for patients to correctly interpret signs that prevent pain symptoms. Furthermore, the abnormal pattern in pain expectancy displayed by fibromyalgia patients could result in ineffective pain coping strategies. Understanding the neural correlates of pain processing and its modulatory factors is crucial to identify treatments for chronic pain syndromes.

Osteoarthritis (OA) is the most prevalent chronic joint disease which increases in frequency with age eventually impacting most people over the age of 65. OA is the leading cause of disability and impaired mobility, yet the pathogenesis of OA remains unclear. Treatments have focused mainly on pain relief and reducing joint swelling. Currently there are no effective treatments to slow the progression of the disease and to prevent irreversible loss of cartilage. Here we demonstrate that stable expression of RORβ in cultured cells results in alteration of a gene program that is supportive of chondrogenesis and is protective against development of OA. Specifically, we determined that RORβ alters the ratio of expression of the FGF receptors FGFR1 (associated with cartilage destruction) and FGFR3 (associated with cartilage protection). Additionally, ERK1/2-MAPK signaling was suppressed and AKT signaling was enhanced. These results suggest a critical role for RORβ in chondrogenesis and suggest that identification of mechanisms that control the expression of RORβ in chondrocytes could lead to the development of disease modifying therapies for the treatment of OA.

Trigeminal neuralgia is a condition confined to the trigeminal nerve, causing one or more branches of facial nerve pain. Surgical treatment options for trigeminal neuralgia include microvascular decompression(MVD), percutaneous balloon compression (PBC), radiofrequency thermocoagulation(RF), percutaneous retrogasserian glycerol rhizotomy(PRGR), gamma knife, etc. Of these treatments, PBC is increasingly being used by clinicians for trigeminal neuralgia. PBC is a simple surgical operation performed to treat trigeminal neuralgia. Owing to its advantages, PBC is favored by many clinicians. In this study, we aimed to emphasize the need to analyze the shape of the balloon, position, compression time, and pressure, as these factors can affect the efficacy of PBC. The relief of pain by balloon compression is related to the shape of the balloon on X-ray, which is the key to the operation. Owing to continued progress and advances in current imaging technologies, clinicians revealed that the precise positioning of the foramen ovale is no longer an intraoperative problem. Instead, the anatomy of Meckel's cave and the shape of the balloon must be the focus to achieve the best treatment effect. For clinicians, PBC is simple and is associated with a short operation time. PBC also has other advantages, such as low cost and immediate postoperative pain relief. The recurrence rate of pain post-PBC is low, despite the occurrence of facial numbness post-op. However, this side effect is reversible and does not affect daily life of the patient. In fact, the patient can be discharged 1-2 days after surgery. Overall, PBC can be considered as one of the preferred surgical methods for the treatment of primary trigeminal neuralgia. In this paper, we explain the main points of PBC operation in detail in terms of Meckel's cave, surgical procedure, complications, discussion of the focus and new progress, etc.

Post-traumatic osteoarthritis is a special type of osteoarthritis and a common disease, with few effective treatments available. α2-Macroglobulin (α2M) is important to chondral protection in post-traumatic osteoarthritis. However, its injection into xenogeneic joint cavities involves safety hazards, limiting clinical applications. Exploring serum α2M-enriching strategies and the therapeutic effect and mechanism of α2M-rich serum (α2MRS) autologous joint injection to treat post-traumatic osteoarthritis has significant value. In the present study, a unique filtration process was used to obtain α2MRS from human and mini pig serum. We evaluated the potential of α2MRS in protecting against post-surgery cartilage degeneration. We identify the potential of α2MRS in reducing the expression of inflammatory cytokines and factors that hasten cartilage degeneration in post-operative conditions leading to post-traumatic osteoarthritis. The potential of α2MRS was analyzed in interleukin-1β induced human chondrocytes and mini pig models. In the chondrocyte model, α2MRS significantly promoted human chondrocyte proliferation and reduced apoptosis and chondrocyte catabolic cytokine gene transcription and secretion. The anterior cruciate ligament autograft reconstruction model of mini pigs was randomized into groups, operated on, and injected with α2MRS or saline. The results showed that α2MRS injection significantly suppressed the levels of inflammatory factors, improved gait, and showed significantly lower cartilage degeneration than the groups that did not receive α2MRS injections. This study highlights the chondroprotective effects of α2MRS, elucidated its potential applications against cartilage degeneration, and could provide a basis for the clinical translation of α2MRS.