Targeting Forkhead box O1-aquaporin 5 axis mitigates neuropathic pain in a CCI rat model through inhibiting astrocytic and microglial activation.

Forkhead box O1 (FoxO1) is a critical molecule in modulating cell growth, differentiation and metabolism, acting as a vital transcription factor. This study explored the role of FoxO1 in chronic constriction injury (CCI)-induced neuropathic pain (NP). Microglial and astrocyte activation was achieved with lipopolysaccharide (LPS, 100 ng/mL) to establish an in-vitro NP model. Morphological alterations in LPS-induced microglia and astrocytes were assayed by light microscopy. The levels of inflammatory cytokines and proteins in microglia and astrocytes were gauged by enzyme-linked immunosorbent assay (ELISA), and Western blot (WB). The CCI-induced NP rat model was constructed for investigating the FoxO1-AQP5 axis in NP. LPS markedly expanded the expression of inflammatory factors and boosted the expression of FoxO1 and AQP5 in microglia and astrocytes. Inhibition of FoxO1 or AQP5 dramatically decreased the LPS-induced inflammation in microglia and astrocytes. In vivo, CCI exacerbated the inflammatory response and NP symptoms and substantially raised the contents of FoxO1 and AQP5 in rats' spinal cord tissues. Intrathecal administration of the Sirt1 agonist Resveratrol abated CCI-induced activation of FoxO1 and AQP5, abrogated CCI-induced mechanical hyperalgesia and thermal hyperalgesia, depressed microglial and astrocyte activation, and declined the generation of pro-inflammatory mediators in spinal cord tissues. Mechanistically, blocking the FoxO1-AQP5 pathway inactivated the ERK and p38 MAPK pathways. Suppressing the FoxO1-AQP5 axis alleviated CCI-induced NP and inflammatory responses by modulating the ERK and p38 MAPK signaling pathways.

Low-Dose Collagenase Chemonucleolysis Combined with Radiofrequency in the Treatment of Lumbar Disc Herniation: A 10-Year Retrospective Study.

OBJECTIVE: This study explored the 10-year efficacy, safety, and prognostic factors of low-dose collagenase chemonucleolysis (CCNL) combined with radiofrequency (RF) in the treatment of lumbar disc herniation (LDH). METHODS: The data of 167 LDH patients were collected. Modified MacNab criteria, Numerical Rating Scale (NRS), and Japanese Orthopedic Association (JOA) scores were, respectively, used to evaluate patients' excellent and good rates, pain degree, and nerve function. The preoperative and 10-year postoperative patients' pain, numbness, and muscle weakness were compared. Patients' complications in perioperative period, recurrent/reappeared LDH, and reoperations were recorded. Finally, the independent risk factors affecting the long-time efficacy were assessed. RESULTS: A total of 126 patients were included. The patients' excellent and good rates were 86.51%-92.86% with no significant difference (P > 0.05). Postoperative NRS and JOA scores significantly improved (P < 0.01), most obvious within 6 months postoperatively. At 10 years postoperatively, 65.08%, 83.95%, and 93.02% of patients' pain, numbness, and muscle weakness were completely relieved (P < 0.05). Perioperative complications occurred in three patients with the rate of 2.38%. Recurrent/reappeared LDH patients were 11 with the ratio of 8.73%; nine of them underwent reoperations with the rate of 7.14%. And patients' probability of fair and poor efficacy at 10 years postoperatively with the course of disease >12 months and the responsibility disc ≥2 were, respectively, 6.005 and 4.227 times that of patients with the course of disease ≤12 months and the responsibility disc = 1 (P < 0.05). CONCLUSION: The combined treatment is effective and safe in the long term. A course of disease >12 months and responsibility disc ≥2 independently reduce efficacy, and a course of disease >12 months has a more significant impact.

TUFT1 Promotes Osteosarcoma Cell Proliferation and Predicts Poor Prognosis in Osteosarcoma Patients.

OBJECTIVE: This study is aimed at exploring the role of TUFT1 in osteosarcomas. METHODS: We investigated the expression of TUFT1 in osteosarcoma cell lines and explored the correlation between TUFT1 expression and prognosis in osteosarcoma patients based on the expression data downloaded from Gene Expression Omnibus (GEO) website. The effects of TUFT1 on osteosarcoma cell proliferation, migration and invasion were investigated by silencing TUFT1 in osteosarcoma MG63 cell line. Finally, western blot was performed to determine the expression changes of MAPK signaling pathway related proteins after silencing TUFT1. RESULTS: We found that the expression of TUFT1 was significantly up-regulated in osteosarcoma cell lines compared with the normal control. Using Kaplan-Meier analysis, we identified that high TUFT1 expression was positively correlated with poor prognosis in osteosarcoma patients. Furthermore, knockdown of TUFT1 remarkably inhibited MG63 cell proliferation, migration and invasion. Using western blot analysis, we found that the phosphorylation levels of MEK and ERK were reduced obviously in MG63 cells after silencing TUFT1 (p<0.01). CONCLUSIONS: Our results demonstrated that TUFT1 plays a promoting role in MG63 cell proliferation and metastasis and has the potential to be a predictor as well as a therapeutic target for osteosarcoma patients.

Cervical spinal epidural abscess following acupuncture and wet-cupping therapy: A case report.

OBJECTIVE: Report of an uncommon complication of acupuncture and wet cupping. METHODS: A 54-year-old man presented with neck pain and fever. Magnetic resonance imaging of the cervical spine revealed an epidural abscess at C4 to T2. RESULTS: The symptoms related to epidural abscess resolved partially after treatment with antibiotics. CONCLUSION: Acupuncture and wet-cupping therapy should be taken into consideration as a cause of spinal epidural abscesses in patients who present with neck pain and fever. Furthermore, acupuncture and wet-cupping practitioners should pay attention to hygienic measures.

[Surgical repair of chronic tears of the second plantar plate].

OBJECTIVE: To explore the operative methods and the short-term effectiveness to repair chronic tears of the 2nd plantar plate. METHODS: Between June 2012 and June 2013, 14 patients with chronic tears of the 2nd plantar plate were treated. There were 4 males and 10 females with an average age of 65.9 years (range, 51-82 years) and with an average disease duration of 6.2 years (range, 5-9 years). The left side was involved in 5 cases and the right side in 9 cases. One patient had simple hammer toe; 2 patients had hallux valgus and claw toe; and 11 patients had hallux valgus and hammer toes. All of them had unstable the 2nd metatarsophalangeal joints. The results of modified Lachman test and drawer test were positive. The surgical treatment included a Weil osteotomy and plantar plate repair operation for rupture via dorsal incision after correcting hallux valgus. RESULTS: Primary healing of incision was obtained in all patients. Twelve patients were followed up 6-12 months (mean, 8.2 months). Hallux valgus, claw toe, and hammer toe were all corrected. The results of modified Lachman test and drawer test were negative at 3 months after operation. Mild pain of the 2nd metatarsophalangeal joint occurred, but no stiff was observed in 2 cases at 6 months after operation. The midfoot and forefoot score of American Orthopedic Foot and Ankle Society (AOFAS) was 90.50 +/- 3.73 at last follow-up, which was significantly higher (t=21.724, P=0.000) than preoperative score (57.33 +/- 4.99). CONCLUSION: The plantar plate is the key to maintain the stability of the metatarsophalangeal joints, and surgical repair can achieve good short-term effectiveness in treating chronic tears of the 2nd plantar plate.