Protectin D1 ameliorates non-compressive lumbar disc herniation through SIRT1-mediated CGRP signaling.

Background. Neuro-inflammatory response promotes the initiation and sustenance of lumbar disc herniation (LDH). Protectin D1 (PD1), as a new type of specialized pro-resolving mediator (SPM), can improve the prognosis of various inflammatory diseases. Recent studies have shown that over representation of calcitonin gene-related peptides (CGRP) may activate nociceptive signaling following nerve injury. Silent information regulator 1 (SIRT1) is ubiquitously expressed in the dorsal horn of the spinal cord and plays a role in the pathogenesis of LDH. In this study, we investigated the analgesic effects of PD1 and elucidated the impact of neurogenic inflammation in the pathogenesis of neuropathic pain induced by non-compressive lumbar disc herniation (NCLDH) in a rat model. Methods. NCLDH models were established by applying protruding autologous nucleus pulposus to the L5 Dorsal root ganglion (DRG). PD1, SIRT1 antagonist or agonist, CGRP or antagonist were administered as daily intrathecal injections for three consecutive days postoperatively. Behavioral tests were conducted to assess mechanical and thermal hyperalgesia. The ipsilateral lumbar (L4-6) segment of the spinal dorsal horn was isolated for further analysis. Alterations in the release of SIRT1 and CGRP were explored using western blot and immunofluorescence. Results. Application of protruded nucleus (NP) materials to the DRG induced mechanical and thermal allodynia symptoms, and deregulated the expression of pro-inflammatory and anti-inflammatory cytokines in rats. Intrathecal delivery of PD1 significantly reversed the NCLDH-induced imbalance in neuro-inflammatory response and alleviated the symptoms of mechanical and thermal hyperalgesia. In addition, NP application to the DGRs resulted the spinal upregulation of CGRP and SIRT1 expression, which was almost restored by intrathecal injection of PD1 in a dose-dependent manner. SIRT1 antagonist or agonist and CGRP or antagonist treatment further confirmed the result. Conclusion. Our findings indicate PD1 has a potent analgesic effect, and can modulate neuro-inflammation by regulating SIRT1-mediated CGRP signaling in NCLDH.

Outcomes, and factors affecting outcomes, following shoulder hemiarthroplasty for proximal humeral fracture repair.

BACKGROUND: Hemiarthroplasty has been applied to treat proximal humeral fracture with variable outcomes. The purpose of this retrospective study was to assess factors affecting outcome in patients following hemiarthroplasty for proximal humeral fracture (PHF) repair. METHODS: Patients with proximal humeral fractures treated over a 6-year period were included. Indications for hemiarthroplasty were severe three-part fractures associated with osteoporosis; four-part fractures with or without dislocation; splitting of the humeral head, or >45% collapse of the humeral head. Surgery outcome and postoperative complications were main outcome measures in this study. RESULTS: Thirty-three of 47 patients were included in the final analysis (mean age 64.3 years, range 43-82). Mean postoperative follow-up was 44.4 (range 36-57) months. Postoperative complications (shoulder dislocation, mild shoulder subluxation, heterotopic ossification) occurred in seven patients. Healing of the greater and lesser tubercles was abnormal or poor in 18 patients. These patients had significantly higher pain scores (4.0 ± 1.1 vs. 2.2 ± 1.1) and significantly lower capacities for active lifting (79.3 ± 9.6 vs. 121.7 ± 24.3), external rotation (20.7 ± 3.7 vs. 39.2 ± 10.3), and Neer scores (79.2 ± 5.7 vs. 90.6 ± 3.6) versus patients who exhibited complete healing (all P < 0.001). Patient age, type of surgical approach, and fracture type were not major influencers of outcome. CONCLUSION: In conclusion, the healing of the greater and lesser tubercles is the major determinant of outcome following hemiarthroplasty for PHF repair.

Bilateral plate fixation for type C distal humerus fractures: experience at a single institution.

Type C fractures of the distal humerus are difficult to treat and typically require open anatomical reduction and internal fixation. Here we describe our experience treating patients with type C distal humerus fractures using a trans-olecranon approach with bilateral plate fixation. Fifty-six patients (30 males, 26 females; mean age 49.8 years) were treated over a period of six years. Thirteen fractures were open and 43 closed; all were caused by falls or traffic accidents. All operations were performed successfully with no intraoperative complications. Mean duration of follow-up was 30 months (range 6-70). Mean duration of fracture healing was 2.8 months (range 2-4). Forty-seven out of 56 patients (84%) suffered no postoperative complications. One patient exhibited symptoms of ulnar nerve injury following surgery (nine exhibited symptoms before and after surgery). Two patients had mild cubitus varus deformities, four delayed olecranon osteotomy site healing, and two heterotopic ossifications. In summary, complications were minimal and outcomes satisfactory in patients with type C distal humerus fractures who underwent bilateral plate fixation via a trans-olecranon approach.

Inhibition of Peripheral ERK Signaling Ameliorates Persistent Muscle Pain Around Trigger Points in Rats.

The purpose of this study was to investigate whether the ERK signaling pathway was involved in ameliorating chronic myofascial hyperalgesia from contused gastrocnemius muscle in rats. We established an animal model associated with myofascial pain syndrome and described the mechanism of muscle pain in an animal model. Changes in the mechanical pain threshold were observed 0.5, 1, 2, 3, 4, 5, 8, 12, 18, and 24 h after ERK inhibitor injection around myofascial trigger points (MTrPs) of the gastrocnemius muscle in rats. Morphological changes in gastrocnemius muscle cells were observed by hematoxylin and eosin (H&E) staining. ERK signaling pathway activation was detected through immunohistochemistry and Western blotting. The main morphological characteristics of injured muscle fibers around MTrPs include gathered circular or elliptical shapes of different sizes in the cross-section and continuous inflated and tapering fibers in the longitudinal section. After intramuscular injection of U0126 (ERK inhibitor), the mechanical pain threshold significantly increased. The reduction in mechanical hyperalgesia was accompanied by reduced ERK protein phosphorylation, myosin light chain kinase (MLCK) protein, p-MLC protein expression, and the cross-sectional area of skeletal muscle cells around MTrPs. An ERK inhibitor contributed to the attenuation of mechanical hyperalgesia in the rat myofascial pain model, and the increase in pain threshold may be related to MLCK downregulation and other related contraction-associated proteins by ERK.

Ideal intraarticular application dose of tranexamic acid in primary total knee arthroplasty: a prospective, randomized and controlled study.

BACKGROUND: Combined use of tranexamic acid (TXA) via intravenous (IV) and intraarticular (IA) routes is more effective in reducing blood loss than any single route in primary total knee arthroplasty (TKA), but the optimal dose of topical administration remains controversial. The aim of this study was to evaluate the efficacy and safety of different combined administration strategies and to determine an ideal IA application dose of TXA. METHODS: A total of 180 patients who underwent primary TKA were randomized to four groups (groups A/B/C/D) with the same single IV dose of 1 g TXA preoperatively and four different IA doses after wound closure: group A (0 g), group B (1 g), group C (2 g), and group D (4 g). The primary outcome measures included wound blood drainage, hemoglobin (Hb) concentration, and blood transfusion. The secondary outcome measures included wound complications, deep vein thrombosis (DVT) and symptomatic pulmonary embolism (PE). RESULTS: A total of 165 patients finished at least 3 months of follow-up visits. The amount of 48-hour blood drainage and calculated total blood loss in four groups decreased with the increased dose of TXA injected via IA route, and no difference was observed between groups C and D (P=0.6237 and P=0.9923, respectively). Hb was significantly higher in groups C and D than in groups A and B at postoperative day 1, 3 and 7, respectively (P<0.0001). Hb in group A was significantly lower than that in groups C and D at 1 month after surgery, whereas no intergroup difference was found in other groups. No intergroup difference was observed regarding DVT, PE or wound complications. CONCLUSIONS: The topical injection of 2 g TXA may have reached the "ceiling effect" of local use. A preoperative IV dose of 1 g TXA combined with an IA dose of 2 g TXA could be an optimal combination regimen.

Targeting bromodomain-containing protein 4 (BRD4) benefits rheumatoid arthritis.

We aimed to explore the effects of bromodomain-containing protein 4 (BRD4) inhibition on tumor necrosis factor (TNF)-α-stimulated human rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) behavior and the therapeutic implications using BRD4 inhibitor JQ1 were explored in vivo. The levels of interleukin (IL)-1ß, IL-6, IL-17 and IL-18 in cultural supernatants from TNFα-stimulated RA-FLS were measured by ELISA. RA-FLS migration and invasion in vitro were investigated using wound healing and Matrigel assay. Expression of signaling pathway proteins was measured by Western blot. The in vivo effects of BRD4 inhibitor JQ1 were elucidated using collagen-induced arthritis (CIA) mice. We found BRD4 silencing reduced the secretion of IL-1ß, IL-6, IL-17 and IL-18 from TNFα-stimulated human RA-FLS. Downregulation of BRD4 inhibited FBS-induced migration and invasion of human RA-FLS. BRD4 silencing decreased the phosphorylation of c-Jun and activation of NFκB in TNFα-stimulated RA-FLS. In vivo, BRD4 inhibitor JQ1 reduced the inflammatory response, autoantibody production and joint damage of CIA model. Our data suggest for the first time that BRD4 inhibition has anti-inflammatory property in RA.

Patelloplasty versus traditional total knee arthroplasty for osteoarthritis.

The purpose of this study was to compare the clinical effects of patelloplasty and traditional patellar management in total knee arthroplasty (TKA) for osteoarthritis. A total of 152 patients with osteoarthritis treated with TKA between January 2004 and December 2005 were retrospectively studied. The patients were randomly divided into 2 groups: the patelloplasty group (group A; n=76) and the traditional treatment group (group B; n=76). Knee Society Score (KSS), Feller patellar score, Lonner patellar score, patient satisfaction, joint range of motion (ROM), and incidence of postoperative anterior knee pain were compared between the groups. Mean follow-up was 55 months (range, 48-71 months) for 132 patients, including 68 patients in group A and 64 in group B. Significant differences were found in KSS functional score, Feller patellar score, Lonner patellar score, and patient satisfaction, but no significant differences were found in ROM and total KSS score between the groups postoperatively. Group A obtained higher KSS scores and patient satisfaction than group B, with no significant difference in postoperative anterior knee pain. Postoperative radiographs revealed a significant difference in patellofemoral congruence between the groups. Patelloplasty relieves pain, enhances patient satisfaction, and improves function better than traditional patellar management in TKA with patellar nonresurfacing.