Small molecule natural compound targets the NF-κB signaling and ameliorates the development of osteoarthritis.

Osteoarthritis (OA) is a multifactorial and chronic disease describing the destruction of cartilage that can lead to defects in the elderly. There is currently no practical strategy that can reverse the OA process. Here, we describe nepetin, a small natural compound with extracellular matrix (ECM) and inflammation regulating functions. In this study, we investigated the therapeutic effects of nepetin on interleukin-1ß (IL-1ß)-induced inflammation in mice chondrocyte and OA model. In chondrocytes, treatment with nepetin inhibited the overexpression of pro-inflammatory cytokines and mediators induced by IL-1ß. Moreover, pretreatment or posttreatment with nepetin also reduced the ECM catabolism and enhanced the ECM anabolism. Mechanistically, nepetin suppressed NF-κB signaling pathway in IL-1ß stimulated chondrocyte. Meanwhile, our molecular docking studies indicated nepetin had a powerful binding capacity to p65. Furthermore, nepetin showed a protective and therapeutic effect on the mouse OA model. To sum up, this study indicated nepetin had a new potential therapeutic option in OA.

[Surgical treatment for posterior Pilon fracture through posterolateral approach].

OBJECTIVE: To explore clinical results of open reduction and internal fixation (ORIF) for posterior Pilon fracture through posterolateral approach. METHODS: Seventeen patients with posterior Pilon fracture were treated through posterolateral approach from February 2010 to April 2013. Among them,including 11 males and 6 females aged from 29 to 59 with an average of 43.4 years old. All fractures were associated with more than 20% of articular surface of distal tibial. The causes of injury included falling down (11 cases), traffic accident (4 cases) and sports injury(6 cases). Fracture classification was based on posterior pilon fracture by YU Guang-rong, including type I (6 cases), type II (2 cases) and type III (6 cases). Fracture healing time, fracture reduction and postoperative complications were observed, AOFAS score were applied to evaluate clinical efficacy. RESULTS: All patients were followed up from 13 to 24 months with an average of 20.5 months. All incisions were healed at stage I, and fractures obtained healing,the time of fracture healing ranged from 12 to 21 weeks with an average of 15.2 weeks. No incision infection, neurovascular injury, bone ununion and fracture deformity were found after operation. Postoperative AOFAS score was 92.0 ± 10.2, and 14 cases got excellent results, 2 good and 1 moderate. CONCLUSION: Posterior pilon fracture through posterolateral approach could obtain effective reduction, stable fixation. It is a safe, simple and effective operation for treating posterior Pilon fracture, and it is worth popularizing.

The Treatment of Fibrosis of Joint Synovium and Frozen Shoulder by Smad4 Gene Silencing in Rats.

Soft tissue fibrosis at the joint induced by inflammation is the pathological basis of frozen shoulder. In the present study, we utilized a lentiviral approach to silence the Smad4 gene in an in vitro fibrosis model of fibroblasts and an in vivo frozen shoulder model. We observed the change in the fibrosis process and the biological indicators of frozen shoulder. The in vitro fibrosis models (Rat myoblasts L6, Rat synovial cell RSC-364 and Rat chondrocytes RCs) were established using TGF-ß1 induction, and the effect of Smad4 gene silencing on fibrosis was analyzed. The method of Kanno A was employed to establish a rat model of frozen shoulder, and Smad4 in the relevant part was knocked down with the lentiviral approach. We then examined the abduction and rotation angles and the length of synovial intima and measured the inflammatory factors in effusion and the fibrotic markers of tissues. We found that Smad4 knockdown suppressed the proliferation and expression of fibrotic markers in L6, RSC-364 and RCs cells induced by TGF-ß1. MMP activity measurements showed that Smad4 knockdown significantly reversed the decrease in MMP activity in these three cell lines that were induced by TGF-ß1. Furthermore, using lentivirus in the rat frozen shoulder model, we found that Smad4 silencing attenuated the inflammatory response and fibrosis. It significantly inhibited the increase of the Vimentin, α-SMA, collagen I and III, Lama1 and Timp1 proteins in synovial tissue as well as the inflammatory factors of TNF-a, IL-1α/ß, IL-6 and IL-10 in effusion. MMP acidity assays revealed that Smad4 silencing inhibited MMP activity in the synovial, cartilage and ligament tissues in the model animals. The assessment of the phosphorylated Smad2/3 in the nuclei isolated from the synovial tissues showed that Smad4 silencing significantly inhibited the phosphorylation and subsequent nuclear translocation of Smad2/3 proteins. Moreover, Smad4-shRNA lentivirus inhibited the decrease in both the abduction and rotation angles caused by immobilization as well as the decrease in the length of the synovial intima. Based on shoulder movement data, Smad4 knockdown can increase the rotation limitation caused by immobilization. In summary, Smad4 silencing can suppress chronic inflammation and fibrosis in joint tissues by inhibiting the TGF-ß/Smad pathway and can play a positive role in the prevention and treatment of joint stiffness.

Minimally invasive plate osteosynthesis vs conventional fixation techniques for surgically treated humeral shaft fractures: a meta-analysis.

BACKGROUND: In this study, we performed a meta-analysis to identify whether minimally invasive plate osteosynthesis (MIPO) was superior to conventional fixation techniques (CFT) for treating humeral shaft fractures. METHODS: A systematic literature search was conducted up to February 2016 in ScienceDirect, Springer, MEDLINE, and PubMed databases for relevant papers that compared the outcomes of MIPO with CFT, such as open reduction with plate osteosynthesis (ORPO) and intramedullary nail (IMN) for treating humeral shaft fractures. Meta-analysis was performed with Review Manager 5.0 software. RESULTS: According to the search strategy, eight studies that covered 391 patients were enrolled, including four randomized controlled trials (RCTs), two prospective cohort trials, and two retrospective cohort trials. Our meta-analysis did not detect any significant difference between MIPO and CFT (IMN and ORPO) in terms of operative time, fracture union rate, and fracture union time. However, MIPO has a less rate of complications and iatrogenic radial nerve palsy than that of ORPO and higher adjacent joint function scores than those of IMN (p < 0.05). CONCLUSIONS: Based on the present evidence, this meta-analysis suggested that MIPO was a better choice for treating humeral shaft fractures than CFT. However, more high-quality randomized trials are still needed to further confirm this conclusion in the future.

[Treatment of thoracolumbar spinal tuberculosis with single posterior debridement, bone grafting, internal fixation and local chemotherapy].

OBJECTIVE: To evaluate the clinical effects of single posterior debridement, bone grafting, internal fixation and local chemotherapy in treating thoracolumbar spinal tuberculosis. METHODS: From February 2009 to September 2012,11 patients with thoracolumbar spinal tuberculosis were treated by single posterior debridement, bone grafting, internal fixation and local chemotherapy. There were 7 males and 4 females, aged from 27 to 65 years old with an average of 53.7 years. The courses of disease was from 3 months to 2 years with the mean of 9 months. According to ASIA standard of spinal cord injury, 3 cases were grade C and 8 cases D. After treatment, clinical effects were evaluated by ASIA grade, visual analogue score (VAS) and Oswestry Disability Index (ODI); kyphosis Cobb angle change was observed by X-rays. RESULTS: Eleven patients were followed up from 12 to 29 months with an average of 18 months. ASIA grade of spinal cord injury, 3 patients with grade C improved to grade D in 2 cases and grade E in 1 case 8 patients with grade D improved to grade E in 7 cases and unchanged in 1 case. VAS decreased from preoperative 6.10 ± 1.30 to 1.70 ± 0.80 at 3 d after operation (P < 0.05). ODI improved from preoperative (68.36 ± 10.41)% to (14.55 ± 8.99)% (P < 0.05) at 3 d after operation. Kyphotic Cobb angle was corrected from preoperative (22.64 ± 4.84)° to (4.27 ± 1.49)° (P < 0.05) on the 3rd day after operation, and angle loss was mild at final follow-up, there was no significant difference between postoperative at 3 d and final follow-up. CONCLUSION: Single posterior debridement, bone grafting, internal fixation and local chemotherapy for the treatment of thoracolumbar spinal tuberculosis can effectively remove the lesion, improve nerve function and correct deformity, has advantage of single incision, little trauma, and low recurrence rate. But it still need long-term and systemic treatment with anti-TB drugs.

[AO elastic intramedullary nailing for the treatment of clavicle fractures].

OBJECTIVE: To evaluate the outcome of Titanium elastic intramedullary nailing (TEN) for the treatment of displaced midclavicular fractures. METHODS: Between February 2010 and February 2013, 62 patients with displaced midclavicular fractures were treated by TEN, including 27 males and 35 females with an average age of 37.6 years old ranging from 15 to 67 years. The course of disease was from 1 to 9 days (means 2.7 days). Thirty-nine cases were treated by closed reduction and 23 cases by assistant small incision. Based on OTA (the Orthopaedic Trauma Association classification) classification, 31 cases of simple fractures involved 5 cases of 06-A1,15 cases of 06-A2,11 cases of 06-A3; 31 cases of wedge fractures involved 4 cases of 06-B1,12 cases of 06-B2,15 cases of 06-B3. Postoperative pain relief were evaluated by VAS score,and operation time,fracture healing time were recorded. After 6 weeks and after removing internal fixation shoulder joint function was evaluated by Constant score, and shoulder joint function were assessed by Herscovici score after 6 weeks. RESULTS: Except 2 cases were lost to follow-up, 2 cases did not remove internal fixation, 3 cases' fractures were nonunion, the remaining 55 patients received follow-up for an average time of 11.4 months. The average preoperative VAS score was 5.20±0.71, and it turned to be 1.550.59 at 3 days after operation. The average operative duration was 40 min (15 to 65 min). The average bone healing time was (2.71±0.54) months (2 to 5 months). No difference about bone healing time was found between simple fractures and wedge fractures,and between the patients treated by closed reduction and assistant small incision. According to Herscovici standard, the shoulder function was excellent in 49 cases, good in 4, fair in 1, and poor in 1. Simple fractures achieved better Constant score than wedge fractures at 6 weeks postoperatively, whereas no difference was found at 4 weeks after fixation removal. CONCLUSION: Titanium elastic nails (TEN) for treatment of displaced midclavicular fractures has advantages of good clinical effect,rapid pain relief,fast recovery of shoulder joint function. For OTA classification type B patients with comminuted fracture can replace steel to achieve very good effect, but to grasp the appropriate.

[Anterior vertebrectomy and plating for spinal tuberculosis].

OBJECTIVE: To study the effect of anterior vertebrectomy, bone grafting and plating in the treatment of spinal tuberculosis. METHODS: Between February 1998 and August 2000, 12 patients with spinal tuberculosis were operated with anterior vertebrectomy, bone grafting and plating. Evaluation including bone fusion rate, correction of deformity and status of spinal lesion was carried out. RESULTS: In an average of ten months, spinal tuberculosis was completely cured and solid bone fusion had taken place in all 12 patients. The time for bone fusion averaged 5.8 months and the average angle of correction of kyphosis was 16 degrees. CONCLUSIONS: Anterior plating following vertebrectomy and bone grafting offers a complete removal of lesion and decompression of the spinal canal as well as reconstruction of spinal stability. Early rehabilitation and an increased curative rate can be expected through this procedure.