Accepted

Migraine is a neurovascular disease with a high disability rate. Acupuncture treatment has emerged as a safe and viable alternative prophylactic therapy that can effectively alleviate the duration and frequency of migraine attacks. However, the therapeutic mechanisms underlying the effects of acupuncture are yet to be systematically elucidated. In this study, we enrolled female patients with migraine without aura ( = 20) and healthy controls ( = 10). Patients received acupuncture treatment on DU20, DU24, bilateral GB13, GB8, and GB20, applied three times per week over the course of 4 weeks for 12 sessions in total. Blood samples were collected from the median cubital vein before and after acupuncture treatment. Proteomic and metabolomic profiling was performed using liquid chromatography-mass spectrometry to determine the characteristics of differentially expressed molecules and expression of their corresponding biological pathways as well as to elucidate the pathogenesis of migraine and the biological effects underlying the treatment of migraine with acupuncture. Proteomic and metabolomic profiling of plasma samples from patients with migraine without aura before and after acupuncture treatment revealed enrichment of immune-related pathway functions and the arginine synthesis pathway. Joint pathway analyses revealed significant enrichment of the pentose phosphate and glycolysis/gluconeogenesis pathways in patients with migraine. The glycolysis/gluconeogenesis and riboflavin metabolism pathways were significantly enriched after acupuncture treatment. The expression levels of various key proteins and metabolites, including α-D-glucose, flavin adenine dinucleotide, biliverdin reductase B, and L-glutamate, were significantly differentially expressed before and after acupuncture treatment in patients with migraine without aura. Treatment of migraine with acupuncture was associated with significant changes in key molecules and pathways, indicative of physiological changes in the trigeminovascular system, glutamate neurotoxicity, and other migraine-related physiological changes. Overall, our comprehensive analysis using proteomic and metabolomic profiling demonstrates that energy metabolism may serve as a key correlative link in the occurrence of migraine and the therapeutic effects of acupuncture treatment. Our findings may facilitate the identification of diagnostic and therapeutic modalities in the ongoing search for effective treatments for migraine attacks.

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.

Ankle sprain occurs by a sudden and extreme inversion and plantarflexion at the ankle joint to cause ligamentous injuries. A portion of ankle sprain patients experience recurrent ankle sprains and develop chronic ankle instability (CAI). The present CAI animal models are single events with severe ligamentous injury using surgical transection of ligaments or manually overextending the ankle. To simulate the mechanical and recurrent sprain injuries in CAI patients, we established a new ankle instability model with multiple ankle injuries using a self-designed machine to sprain the ankle with a controlled inversion angle and speed. Male C57BL/6J mice were used and respectively subjected to a sham operation, calcaneofibular ligament (CFL) transection, and mechanical ankle sprains. Three mechanical sprains were performed on the 13th and 185th day after the initial mechanical ankle sprain. The first mechanical sprain and CFL transection induced ankle injury as indicated by an average of a 62% decrease in ankle pressure pain threshold and a 114% increase in the ankle thickness compared with the contralateral untreated ankle. The second and third mechanical sprains induced recurrent ankle injuries. The foot slips during beam tests were increased after mechanical ankle sprains but not after CFL transection, indicating the induction of motor balance deficits. Multiple mechanical ankle sprains induced significant gait changes in longer duration of stance (an average of 194% increase), swing (134%), and step cycle (147%) compared with CFL transection or sham operation, and slower walking speed (78% reduction) and shorter step distance (91%) after the third sprain. These results elucidate that multiple mechanical sprains, which induce recurrent ankle injuries, balance deficits, and gait changes, are a good model for investigating the mechanisms of CAI induced by recurrent sprain injuries.