Koumine inhibits RANKL-induced ubiquitination and NF-κB activation to prevent ovariectomy and aging-induced bone loss.

Osteoporosis (OP) is a bone remodeling disease characterized by an imbalance between bone resorption and formation. Osteoclasts are the primary therapeutic targets for treating bone destruction. Koumine (KM), the most bioactive component in Gelsemium alkaloids, exhibits antitumor, immunosuppressive, anti-inflammatory, and analgesic properties. However, the effects of bone loss have not been well studied. This study conducted in vitro and in vivo verification experiments on KM. The results showed that KM inhibited bone resorption and tartrate-resistant acid phosphatase positive (TRAP+) osteoclasts development by mature osteoclasts in a dose-dependent manner. Moreover, KM prevented OVX-induced OP in vivo and potentially inhibited ubiquitination, a process closely related to various biological activities, including protein interaction, transcription, and transmembrane signal transduction regulation, especially within the nuclear factor-κB (NF-κB) pathway. Previous studies have demonstrated that several proteins ubiquitination promotes osteoclastogenesis, our study indicated that KM inhibits early NF-κB activation and receptor activator of NF-κB ligand induced ubiquitination, a critical factor in osteoclast differentiation. In conclusion, our research suggests that KM holds potential as an effective therapeutic agent for OP.

The impact of the union of lesser trochanter fragments after intramedullary fixation of trochanteric femoral fractures: an X-ray based study.

BACKGROUND: Displacement of the lesser trochanter (LT) is not uncommon after managing intertrochanteric femoral fractures and the influence of nonunion of the LT-fragment on clinical outcomes remains controversial. This study aimed to investigate the relationship between the displacement distance and union of the LT-fragment and evaluate the influence of LT-fragment nonunion on hip function and complications. METHODS: This retrospective study included patients with intertrochanteric fractures and displaced LT treated with intramedullary fixation at Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine from June 2015 to July 2017. The patients were grouped as union and nonunion of the LT-fragment at 1 year. The LT-fragment displacement distance of LT was measured by the anterior-posterior radiographs. RESULTS: Thirty-one and 22 patients showed union and nonunion at 1 year, respectively. The nonunion group had a higher postoperative complication rate than the union group (59% vs. 29%, P = 0.047), especially mechanical complications (45% vs. 6%, P = 0.001). There was no significant difference in hip function between the two groups (P > 0.05). The receiver operating characteristic (ROC) curve revealed an area under the curve of 0.933 of displacement ratio. Patients with a displacement ratio > 0.35 were more likely to have nonunion of the LT-fragment. CONCLUSIONS: The displacement ratio might be a reliable predictor of LT-fragment union. The incidence of postoperative complications might increase with LT-fragment nonunion.

[Comparative study on curative effect of minimally invasive locking plate for the treatment of intra-articular calcaneal fractures via sinus tarsi approach].

OBJECTIVE: To compare clinical efficacy of minimally invasive locking plate and anatomic locking plate in treating intra-articular calcaneal fractures via sinus tarsi approach. METHODS: A retrospective analysis was conducted of 48 patients with intra-articular calcaneal fractures treated with surgery via sinus tarsi approach from July 2016 to June 2017. According to differernt methods of internal fixation, the patients were divided into minimally invasive locking plate group and anatomic locking plate group. In minimally invasive locking plate group, there were 14 males and 10 females, aged from 27 to 46 years old with an average age of (38.70±5.58) years old, 18 patients were typeⅡand 6 patients were type Ⅲ according to Sanders classification. In anatomic locking plate group, there were 17 males and 7 females, aged from 26 to 46 years old with an average age of (37.10±6.44) years old, 16 patients were typeⅡ and 8 patients were type Ⅲ according to Sanders classification. Operative time, visual analogue scale (VAS), postoperative complications between two groups were compared, and Böhler angle, Gissane angal, calcaneal width and height were recorded and compared between two groups at 1 week after operation and final follow up. The functional effect was assessed according to Maryland foot function score at final follow up. RESULTS: All patients were followed up for (14.10±1.94) months (ranged 12 to 18 months). All patients were obtained bone union from 8 to 16 weeks with an average of (10.60±2.25) weeks. Operation time, VAS score and complication rate in minimally invasive locking plate group were (69.50±7.51) min, (2.80±1.07) and 2 cases respectively, and (77.50±7.15) min, (3.80±1.09) and 8 cases in anatomic locking plate group respectively, there were statistical difference between two groups (P<0.05). However, there were no statistically differences in Maryland foot function score, Böhler angle, Gissane angle, calcaneal width and height at 1 week after opertaion and final follow-up between two groups (P>0.05). CONCLUSION: Compare with anatomic locking plate, minimally invasive locking plate via sinus tarsi approach for Sanders typeⅡ and Ⅲ intra-articular calcaneal fractures could obtain similar reliable fixation and functional recovery with more simple operation, shorter operative time, lighter postoperative pain and less complications.

Administration of mircoRNA-135b-reinforced exosomes derived from MSCs ameliorates glucocorticoid-induced osteonecrosis of femoral head (ONFH) in rats.

Exosomes were found to exert a therapeutic effect in the treatment of osteonecrosis of the femoral head (ONFH), while miR-135b was shown to play an important role in the development of ONFH. In this study, we investigated the effects of concomitant administration of exosomes and miR-135b on the treatment of ONFH. A rat mode of ONFH was established. TEM, Western blotting and nanoparticle analysis were used to characterize the exosomes collected from human-induced pluripotent stem cell-derived mesenchymal stem cells (hiPS-MSC-Exos). Micro-CT was used to observe the trabecular bone structure of the femoral head. Real-time PCR, Western blot analysis, IHC assay, TUNEL assay, MTT assay and flow cytometry were performed to detect the effect of hiPS-MSC-Exos and miR-135b on cell apoptosis and the expression of PDCD4/caspase-3/OCN. Moreover, computational analysis and luciferase assay were conducted to identify the regulatory relationship between PDCD4 mRNA and miR-135b. The hiPS-MSC-Exos collected in this study displayed a spheroidal morphology with sizes ranging from 20 to 100 nm and a mean concentration of 1 × 1012 particles/mL. During the treatment of ONFH, the administration of hiPS-MSC-Exos and miR-135b alleviated the magnitude of bone loss. Furthermore, the treatment of MG-63 and U-2 cells with hiPS-MSC-Exos and miR-135b could promote cell proliferation and inhibit cell apoptosis. Moreover, PDCD4 mRNA was identified as a virtual target gene of miR-135b. HiPS-MSC-Exos exerted positive effects during the treatment of ONFH, and the administration of miR-135b could reinforce the effect of hiPS-MSC-Exos by inhibiting the expression of PDCD4.

[Case-control study on minimally invasive surgery and conventional open plating for displaced midshaft clavicular fracture based on 3D-print].

OBJECTIVE: To compare clinical effect of minimally invasive surgery and conventional open plating for acute displaced midshaft clavicle fracture based on 3D-print. METHODS: From July 2016 and December 2016, 40 patients with acute displaced midshaft clavicle fractures were retrospectively analyzed. The patients were divided into 3D minimally invasive surgery group (group A) and conventional open plating group (group B) according to different surgical incisions and whether to use 3D printing. In group A, including 11 males and 9 female, aged from 19 to 57 years old with an average of(37.2±9.3)years old; type 2A2 were 4 patients, type 2B1 were 9 patients and type 2B2 were 7 patients according to Robinson classification. In group B, including 13 males and 7 female, aged from 17 to 54 years old with an average of(35.1±9.5) years old; type 2A2 were 5 patients, type 2B1 were 8 patients and type 2B2 were 7 patients according to Robinson classification. Operative time, blood loss, length of incision, fracture healing time, complications were observed and compared between two groups, DASH score and Constant score of shoulder joint were evaluated at 12 months after operation. RESULTS: Forty patients were followed up from 12 to 18 months with an average of(15.1±2.0) months. All fractures were healed, healing time in group A ranged from 12 to 18 months with an average of (14.3±1.7) months, in group B ranged from 11 to 18 months with an average of (14.4±1.9) months, while there was no statistical differences between two groups(P>0.05). No differences in blood loss between two groups(P>0.05). Operative time, length of incision in group A was less than that of group B (P<0.05). There were no significant differences in DASH score and Constant score at 12 months between two groups(P>0.05). One patient in group A occurred complication, and 6 patients in group B occurred compilations, and has statistical differences between two groups(P<0.05). CONCLUSIONS: Minimally invasive technique based on 3D-print could resolve some difficulties of minimally invasive surgery effectively and achieve fracture healing and functional recovery similar to traditional open reduction with more beautiful incision, less complication, shorter operation time.

Comparison of post-operative numbness and patient satisfaction using minimally invasive plate osteosynthesis or open plating for acute displaced clavicular shaft fractures.

BACKGROUND: Anterior chest wall numbness after plate fixation of clavicular shaft fractures is a common complication. This is usually related to damage of the branches of the supraclavicular nerve in conventional open plating. We investigated whether the use of minimally invasive plate osteosynthesis could reduce the incidence of post-operative numbness and improve patients' satisfaction compared to open plating. METHODS: Between August 2012 and October 2015, 73 patients with acute clavicle shaft fracture (Robinson classification 2A2-2B2) were treated with plate fixation at our institution. Thirty-eight patients underwent minimally invasive plate osteosynthesis (MIPO), and the other 35 patients received conventional open reduction and internal fixation (ORIF). The incidence of anterior chest wall numbness, numbness area, and patient satisfaction were evaluated at 2 weeks, 3 months and 1 year after the operation by questionnaires. Shoulder joint function was evaluated using the Constant-Murley score and the Disability of the Arm, Shoulder and Hand (DASH) score, and pain was measured using a Visual Analogue Scale (VAS). RESULTS: The patients in the MIPO group had a lower incidence and smaller area of anterior chest wall numbness than the ORIF group at each follow-up interval. The patients who underwent MIPO reported higher satisfaction with the operation. There was no significant difference in the Constant-Murley score, DASH score and VAS of the 2 groups at 1-year follow-up. CONCLUSION: The MIPO technique for clavicle shaft fractures is an effective way to reduce post-operative numbness and improve patients' satisfaction compare to conventional open plating. Surgeons could consider using this technique as an alternative procedure to prevent iatrogenic supraclavicular nerve damage and subsequent anterior chest wall numbness.

MicroRNA-542-3p suppresses tumor cell proliferation via targeting Smad2 inhuman osteosarcoma.

Osteosarcoma (OS) is an aggressive malignant neoplasm that arises from primitive transformed cells of mesenchymal origin, and that exhibits osteoblastic differentiation and produces malignant osteoid. MicroRNA (miR)-542-3p has been reported to serve a crucial role in the initiation and development of several types of human cancer. However, whether miR-542-3p is involved in tumorigenesis and tumor progression of OS remains unclear. In the present study, the expression of miR-542-3p in OS cells and patients with OS, and its functional mechanism in OS were investigated. The data demonstrated that expression of miR-542-3p was significantly decreased in OS tissues and cell lines, and that restoration of miR-542-3p expression in OS cells inhibited cell proliferation and induced cell apoptosis. Through bioinformatics analysis and luciferase reporter assays, the present study identified that miR-542-3p directly targeted Smad2 mRNA and negatively regulated the expression of Smad2 at the protein level in OS cells. Furthermore, it was confirmed that OS tumor tissues with a low expression of miR-542-3p exhibited markedly higher Smad2 expression. Finally, through the use of gain of function and rescue experiments, the present study demonstrated that restoration of miR-542-3p was able to suppress the growth and proliferation of OS cells through directly targeting Smad2. To the best of our knowledge, this is the first study to demonstrate that decreased expression of miR-542-3p serves a role in tumor suppression in OS pathogenesis through targeting Smad2. These results will aid in elucidating the functions of miR-542-3p, and suggest that miR-542-3p may serve as a tumor suppressor gene and a promising therapeutic target of OS.

[Comparison of internal fixation and semi-shoulder arthroplasty in treating proximal humerus comminuted fractures in elderly].

OBJECTIVE: To explore clinical effectiveness of internal fixation and semi-shoulder arthroplasty in treating proximal humerus comminuted fractures in elderly. METHODS: From October 2009 and October 2011, 32 patients aged over 60 years old with three and four-part fractures of proximal humeral were treated with internal fixation (20 cases) and semi-shoulder arthroplasty (12 cases). In internal fixation group, there were 6 males and 14 females aged from 63 to 82 years old (ranged, 71.50 +/- 5.45), 8 cases with three-part fracture and 12 cases with four-part fracture, and treated with open reduction and locking plate internal fixation. While in semi-shoulder arthroplasty group, there were 4 males and 8 females aged from 61 to 85 years old (ranged, 72.80 +/- 6.80), 5 cases with three-part fracture and 7 cases with four-part fracture, and treated with semi-shoulder arthroplasty. Postoperative complications were observed, EQ-5D was used to evaluate quality of life, and Constant-Murley score was used to assess functional outcomes. RESULTS: All patients were followed up from 12 to 24 months with an average of 18 months. All injuries were healed at stage I . Two cases in internal fixation group occurred severe complications, including 1 case with screw fracture, 1 case with avascular necrosis of humeral head. EQ-5D in interal fixation group and semi-shoulder arthroplasty group were respectively 0.65 +/- 0.12, 0.67 +/- 0.12, Constant-Murley score respectively was 63.20 +/- 11.35 and 66.80 +/- 11.96, and with no statistical meaning between two goups (P>0.05). CONCLUSION: There is no difference in qulity of life and functional recovery for the treatment of proximal humerus comminuted fractures by open reduction and internal fixation and semi-shoulder arthroplasty. However, the complication rate in semi-shoulder arthroplasty was lower than that of internal fixation group.