circ_0029463 promotes osteoclast differentiation by mediating miR-134-5p/Rab27a axis.

OBJECTIVE: Osteoporosis is the imbalance in bone homeostasis between osteoblasts and osteoclasts. In this study, we investigated the effects of the circ_0029463/miR-134-5p/Rab27a axis on RANKL-induced osteoclast differentiation. METHODS: RT-qPCR and western blotting were used to detect the expression of circ_0029463, miR-134-5p, and Rab27a in tissues from patients with osteoporosis and in RANKL-induced osteoclasts. Osteoclast differentiation was verified by TRAP staining. Osteoclast biomarkers, including NFATc1, TRAP, and CTSK, were measured. The target and regulatory relationships between circ_0029463, miR-134-5p, and the Rab27a axis were verified using RIP, dual-luciferase reporter gene, and RNA pull-down assays. RESULTS: Elevated expression of circ_0029463 and Rab27a and decreased miR-134-5p expression were observed in the tissues of patients with osteoporosis, and a similar expression pattern was observed in RANKL-induced osteoclasts. Suppression of circ_0029463 expression or miR-134-5p overexpression curbed RANKL-induced osteoclast differentiation, whereas such an effect was abolished by Rab27 overexpression. circ_0029463 sponges miR-134-5p to induce Rab27a expression. CONCLUSION: circ_0029463 sponges miR-134-5p to abolish its suppressive effect of miR-134-5p on Rab27a expression, thereby promoting osteoclast differentiation.

[Preparation and properties of a new artificial bone composite material].

Objective: To study the preparation and properties of the hyaluronic acid (HA)/α-calcium sulfate hemihydrate (α-CSH)/ß-tricalcium phosphate (ß-TCP) material (hereinafter referred to as composite material). Methods: Firstly, the α-CSH was prepared from calcium sulfate dihydrate by hydrothermal method, and the ß-TCP was prepared by wet reaction of soluble calcium salt and phosphate. Secondly, the α-CSH and ß-TCP were mixed in different proportions (10∶0, 9∶1, 8∶2, 7∶3, 5∶5, and 3∶7), and then mixed with HA solutions with concentrations of 0.1%, 0.25%, 0.5%, 1.0%, and 2.0%, respectively, at a liquid-solid ratio of 0.30 and 0.35 respectively to prepare HA/α-CSH/ ß-TCP composite material. The α-CSH/ß-TCP composite material prepared with α-CSH, ß-TCP, and deionized water was used as the control. The composite material was analyzed by scanning electron microscope, X-ray diffraction analysis, initial/final setting time, degradation, compressive strength, dispersion, injectability, and cytotoxicity. Results: The HA/α-CSH/ß-TCP composite material was prepared successfully. The composite material has rough surface, densely packed irregular block particles and strip particles, and microporous structures, with the pore size mainly between 5 and 15 µm. When the content of ß-TCP increased, the initial/final setting time of composite material increased, the degradation rate decreased, and the compressive strength showed a trend of first increasing and then weakening; there were significant differences between the composite materials with different α-CSH/ß-TCP proportion ( P<0.05). Adding HA improved the injectable property of the composite material, and it showed an increasing trend with the increase of concentration ( P<0.05), but it has no obvious effect on the setting time of composite material ( P>0.05). The cytotoxicity level of HA/α-CSH/ß-TCP composite material ranged from 0 to 1, without cytotoxicity. Conclusion: The HA/α-CSH/ß-TCP composite materials have good biocompatibility. Theoretically, it can meet the clinical needs of bone defect repairing, and may be a new artificial bone material with potential clinical application prospect.

Synthesis and Properties of Magnetic Fe3O4/PCL Porous Biocomposite Scaffolds with Different Sizes and Quantities of Fe3O4 Particles.

In clinical practice, to treat diseases such as osteosarcoma or chondrosarcoma with broad surgical ostectomy, it would be ideal to have scaffolds that not only fill up the bone void but also possess the ability to regulate the subsequent regimes for targeted chemotherapy and/or bone regeneration. Magnetic targeting of therapeutic agents to specific sites in the body provides certain advantages such as minimal side-effects of anti-cancer drugs. The objective of this study was to characterize novel magnetic scaffolds that can be used as a central station to regulate the drug delivery of a magnetic nanoparticle system. Different sizes and quantities of Fe3O4 particles were mixed with poly-ε-caprolactone (PCL) to construct the magnetic scaffolds, and their mechanical properties, degradation performance, and cell biocompatibility were evaluated. It appeared that the presence of Fe3O4 particles influenced the magnetic, mechanical, and biological performances of the scaffolds. The prepared bio-nanocomposite scaffolds provided predominantly magnetic/superparamagnetic properties. Scaffolds with a micron-sized Fe3O4 to PCL weight (wt) ratio of 0.1:0.9 exhibited higher mechanical performances among samples, with Young's modulus reaching 1 MPa and stiffness, 13 N/mm. Although an increased Fe3O4 particle proportion mildly influenced cell growth during the biocompatibility test, none of the Fe3O4/PCL scaffolds showed a cytotoxic effect.

Glomus Tumors of the Distal Phalanx: A Retrospective Review of Clinical Diagnosis and Treatment.

Glomus tumors (GTs) are rare and typically occur in distal digital bones, with a majority of cases comprising benign vascular tumors. The current study retrospectively reviewed 10 cases of GTs treated by the authors between January 2009 and December 2016. In 9 cases, the GTs were subungual; 1 case was periungual. The affected fingers included 2 thumbs, 3 index fingers, 3 middle fingers, and 2 little fingers. The GTs showed characteristic signs and symptoms. All patients underwent tumor excision. Pathological examination found a thin layer of fibrous membrane surrounding the excised tumor body, which contained small vessels surrounded by multilayered tumor cells. No recurrence was seen during follow-up. The results of this study suggested the following: (1) whole tumor excision is key to preventing GT recurrence; and (2) in case of considerable phalangeal cortex erosion, K-wire fixation followed by autogenous bone grafting can produce satisfactory outcomes, although accurate evidence-based indications for this management need to be established. [Orthopedics. 2022;45(2):e101-e106.].

[Double internal fixations of clavicle and scapula and intraoperative reduction of glenopolar angle for treatment of floating shoulder injuries].

OBJECTIVE: To investigate the effectiveness of double internal fixations of clavicle and scapula and intraoperative reduction of glenopolar angle in the treatment of floating shoulder injuries. METHODS: Between January 2010 and June 2019, 13 patients with floating shoulder injury were treated with double internal fixation of clavicle and scapula and intraoperative reduction of glenopolar angle. There were 11 males and 2 females with an average age of 48 years (range, 25-65 years). The causes of injury included falling from height in 2 cases, traffic accident injury in 3 cases, heavy object injury in 2 cases, and other injuries in 6 cases. There were 2 cases of Ⅰ-B-3 type, 1 case of Ⅰ-C-2 type, 1 case of Ⅰ-C-3 type, 3 cases of Ⅱ-B-2 type, 1 case of Ⅱ-B-3 type, 1 case of Ⅱ-B-4 type, 2 cases of Ⅱ-C-2 type, 1 case of Ⅱ-C-4 type, and 1 case of Ⅱ-D-3 type according to the classification of floating shoulder injury. All patients had unilateral clavicle fracture with scapular neck fracture, 1-4 superior shoulder suspensory complex (SSSC) injuries. The time from injury to operation was 7-17 days, with an average of 12 days. The glenopolar angle, subacromail space, anteroposterior inclination angle of scapular glenoid, scapular glenoid up and down angle were measured before and after operation; Constant-Murly score and Herscovici score were used to evaluate the recovery of shoulder joint function. RESULTS: All incisions healed by first intention, and there was no early postoperative complications such as infection. All 13 cases were followed up 12-48 months, with an average of 25.2 months. Both the clavicle and the scapula had bone union, and the average healing time was 6 months and 4 months respectively. There were no complications such as nonunion, shoulder deformity, plate fracture or failure of internal fixation, acromion impingement syndrome, and frozen shoulder. At last follow-up, the glenopolar angle, subacromail space, anteroposterior inclination angle of scapular glenoid, and scapular glenoid up and down angle were all corrected significantly ( P<0.05). The pain, function, activity, muscle strength scores, and total score in Constant-Murly score were significantly improved when compared with preoperative scores ( P<0.05). According to the Herscovici scoring standard, the shoulder joint function was evaluated as excellent in 8 cases, good in 3 cases, and fair in 2 cases. The excellent and good rate was 84.6%. CONCLUSION: Double internal fixation of clavicle and scapula to stabilize SSSC and reduct glenopolar angle during operation is an effective method for treating the floating shoulder injury.

Long non-coding RNA (LncRNA) MRPL23-AS1 promotes tumor progression and carcinogenesis in osteosarcoma by activating Wnt/ß-catenin signaling via inhibiting microRNA miR-30b and upregulating myosin heavy chain 9 (MYH9).

Long non-coding RNA (LncRNA) contributes to the occurrence and development of osteosarcoma (OS), although the underlying mechanism is not clear. In the present study, we showed that lncRNA MRPL23-AS1 was remarkably increased in OS tissues and cell lines. Stable knockdown of MRPL23-AS1 evidently attenuated cell viability and invasive ability, meanwhile inhibited in vivo tumor growth and dissemination. In terms of mechanism, luciferase reporter, RNA pull-down and fluorescence in situ hybridization (FISH) assays showed that MRPL23-AS1 competitively interacted with miR-30b, increasing myosin heavy chain 9 (MYH9) expression, a trans- activator of ß-catenin, resulting in the activation of Wnt/ß-catenin pathway, thereby promoting OS tumorigenesis and metastasis. Importantly, high MRPL23-AS1 was positively correlated with MYH9, while conversely correlated with miR-30b, suggesting that the regulatory axis of MRPL23-AS1/miR-30b/MYH9 does exist in OS. Clinically, OS patients with high MRPL23-AS1 had larger tumor size, higher stage and easier metastasis than those with low MRPL23-AS1, moreover, MRPL23-AS1 was identified as an adverse prognostic factor for OS survival. In conclusion, our results show that MRPL23-AS1 is a key oncogenic lncRNA in OS, targeting of MRPL23-AS1 may be a promising treatment for OS patients.

[Analysis of effectiveness of greater trochanteric osteotomy approach and K-L posterior approach in patients with type â £ Pipkin fracture].

OBJECTIVE: To investigate the effectiveness of two surgical approaches in the treatment of type Ⅳ Pipkin fracture. METHODS: The clinical data of 15 patients with type Ⅳ Pipkin fracture treated surgically between July 2013 and June 2018 were retrospectively analyzed. According to different surgical approaches, they were divided into group A (8 cases, using K-L posterior approach) and group B (7 cases, using greater trochanter osteotomy approach). There was no significant difference in gender, age, cause of injury, and interval from injury to operation between the two groups ( P>0.05). The incision length, operation time, intraoperative blood loss, hospital stay, fracture healing time, and complications of the two groups were recorded. Hip joint function recovery was evaluated according to Thompson-Epstein functional evaluation system. RESULTS: All the 15 patients were followed up 1-5 years, with an average of 2.5 years. There was no significant difference in operation time between the two groups ( t=14.681, P=0.100); the incision length, intraoperative blood loss, and fracture healing time in group A were all greater than those in group B, and the hospital stay was shorter than that in group B, showing significant differences ( P<0.05). In group A, 1 patient presented hip pain, clasthenia, and limited mobility after operation, 1 patient presented ossifying myositis, 1 patient presented osteonecrosis of the femoral head, 1 patient presented fat liquefaction of incision, and 1 patient presented sciatica, with a complication incidence of 62.5%. Postoperative hip pain occurred in 1 patient and ossifying myositis in 2 patients in group B, with a complication incidence of 42.9%. There was no significant difference in the incidence of complications between the two groups ( χ 2=-0.735, P=0.462). At last follow-up, according to Thompson-Epstein functional evaluation system, the results in group A were excellent in 3 cases, good in 2 cases, fair in 2 cases, and poor in 1 case, with an excellent and good rate of 62.5%; in group B, the results were excellent in 4 cases, good in 2 cases, and fair in 1 case, and the excellent and good rate was 85.7%. There was no significant difference in good and fair rate between the two groups ( χ 2=-0.990, P=0.322). CONCLUSION: K-L posterior approach is more convenient in the fracture treatment during operation, but it has greater trauma, greater vascular damage, and more blood loss. The greater trochanter osteotomy approach can better protect the blood supply of femoral head, shorten the operation time, reduce intraoperative blood loss, and reduce postoperative complications. It is an ideal way in the surgical treatment of type Ⅳ Pipkin fracture.

3D Bioprinting of shear-thinning hybrid bioinks with excellent bioactivity derived from gellan/alginate and thixotropic magnesium phosphate-based gels.

3D Bioprinting is expected to become a strong tool for regenerative medicine, but satisfactory bioinks for the printing of constructs containing living cells are lacking due to the rigorous requirement of high printability and biocompatibility, which are often contradictory. Here, we have reported the development of a novel hybrid bioink by combining rigid gellan gum (GG), flexible sodium alginate (SA), and a bioactive substance thixotropic magnesium phosphate-based gel (TMP-BG). The ratio of these components was first optimized to obtain satisfactory gelating, mechanical, rheological, and printing properties. The formulated hybrid GG-SA/TMP-BG bioink had a good printability due to the shear-thinning and its multiple cross-linking by Mg2+ and Ca2+. The tunable mechanical performance of the hybrid bioink could simulate various extracellular matrices of the different tissues and support integrity of 3D printing constructs. Moreover, the hybrid bioink induced apatite deposition during immersion in simulated body fluids, and also promoted cell proliferation in vitro. MG-63 osteosarcoma cells were dispersed in the bioink and printed into 3D constructs. The cells exhibited good cell survival due to the shear-thinning property of the bioink and the ion concentration used for cross-linking. The proliferation rate of the cells also significantly exceeded those in non-printed samples. Confocal microscopy revealed a homogeneous distribution of cells in the printed constructs, and survival for more than 7 d. In vivo animal experiments showed that the hybrid bioink without cells could induce osteochondral repair. Therefore, this hybrid bioink has good printability, biocompatibility, mechanical support, and bioactivity, which is expected to have promising applications in 3D bioprinting.

An Antisense Oligonucleotide Drug Targeting miR-21 Induces H1650 Apoptosis and Caspase Activation.

Non-small cell lung cancer is the most common malignant tumor in the world. Currently, chemotherapy is still the major method for non-small cell lung cancer treatment, but the problem of cancer drug resistance still exists, so we designed 5 different phosphorothioate oligonucleotides to silence key genes in tumor cell development, which could help avoid inducing cancer cell drug resistance. MicroRNAs have been shown to play a crucial role in the pathogenesis and progression of many malignancies, such as breast, colon, lung, and pancreatic cancer. According to the data from the Gene Expression Omnibus database, miR-21 has been reported to be one of the top 20 differentially expressed microRNAs screened using the Morpheus online tool, and miR-21 has been revealed to regulate a series of biological behaviors in cancer cells, including cell proliferation, migration, invasion, metastasis, and apoptosis. In recent years, gene therapy has emerged as a new therapeutic strategy for cancer treatment. Antisense oligonucleotides have recently been suggested as a novel approach for targeting microRNAs by antisense-based gene silencing. Five phosphorothioate oligonucleotides were designed, synthesized, and screened for anticancer activity. Reverse transcription-polymerase chain reaction was used to detect the relative expression of miR21. Among these 5 sequences, only phosphorothioate oligonucleotide 4 inhibited the proliferation of H1650 cells, and this effect was due to the induction of cancer cell apoptosis by activating the caspase-8 apoptotic pathway. In conclusion, this research confirmed the anticancer activity of phosphorothioate oligonucleotide 4 and revealed the underlying mechanism, which has the potential to be a novel anticancer strategy.

[Development and clinical application of a new type of anatomical locking plate for sternoclavicular joint fracture and dislocation].

Objective: To report a new type of anatomical locking plate for sternocalvicular joint, and investigate its effectiveness in treatment of sternoclavicular joint fracture and dislocation. Methods: A new type of anatomical locking plate for sternoclavicular joint was developed, which accorded with the anatomical features and biomechanical characteristics of Chinese sternoclavicular joint. By adopting the method of clinical randomized controlled study, 32 patients with the sternoclavicular joint fracture and dislocation who met the selection criteria between June 2008 and May 2015 were randomly divided into groups A and B ( n=16), and the patients were treated with new anatomic locking plate and distal radial T locking plate internal fixation, respectively. There was no significant difference between 2 groups in gender, age, injured side, body mass index, cause of injury, type of injury, the time from injury to operation, and preoperative Rockwood grading score ( P>0.05). The operation time, intraoperative blood loss, incision length, hospitalization time, and postoperative complications in 2 groups were recorded, and the effectiveness was evaluated by Rockwood grading score. Results: The operations of 2 groups completed successfully. The operation time, intraoperative blood loss, and hospitalization time in group A were significantly less than those in group B ( P<0.05), but there was no significant difference in the incision length between 2 groups ( t=0.672, P=0.507). All the patients were followed up 18-30 months (mean, 24 months). In group A, there were 1 case of sternoclavicular joint pain and 2 cases of wound infection; in group B, there were 1 case of sternoclavicular joint pain, 1 case of internal fixation loosening, and 1 case of sternoclavicular joint re-dislocation; there was no significant difference in complication incidence between 2 groups ( P=1.000). The Rockwood grading scores at each time point after operation in 2 groups were significantly higher than those before operation. At 1 month after operation, the Rockwood grading score in group A was significantly higher than that in group B ( t=2.270, P=0.031); but there was no significant difference in the Rockwood grading scores between the 2 groups at 6 months and at last follow-up ( P>0.05). At last follow-up, according to the Rockwood scoring standard, the results of group A were excellent in 13 cases, good in 2 cases, poor in 1 case, the excellent and good rate was 93.75%; the results of group B were excellent in 11 cases, good in 4 cases, poor in 1 case, and the excellent and good rate was 93.75%; there was no significant difference between 2 groups ( Z=-0.748， P=0.455). Conclusion: The new type of anatomic locking plate accords with the Chinese anatomical characteristics. It has the advantages of easy operative procedure, less surgical trauma, shorter operation time, less intraoperative blood loss, shorter hospitalization time, and it can achieve better results in the treatment of sternoclavicular joint fracture and dislocation.

[Development and biomechanical study of anatomical locking plate of sternoclavicular joint].

Objective: To develop an anatomical locking plate in accordance with the anatomical characteristics of the sternoclavicular joint, which is reliable fixation and easy to operate, so as to provide an ideal internal fixation device for the treatment of sternoclavicular joint dislocation or peripheral fractures. Methods: Gross measurement and CT measurement were performed on the 8 adult antiseptic and moist cadaver specimens (16 sides) to measure the parameters of surrounding bone structure of the sternoclavicular joint. The parameters included the thickness of presternum, sternal notch width, anteroposterior diameter of proximal 1/3 of clavicle, upper and lower diameters of proximal 1/3 of clavicle, angle between proximal end of clavicle and presternum in coronal plane, and angle of thoracoclavicular joint at anatomic position forward. According to the anatomical parameters and biomechanical properties of the specimens, the anatomical locking plate was designed and developed. The sternoclavicular ligament and joint capsule of all the specimens were completely cut off to make the sternoclavicular joint dislocation model. The left and right sternoclavicular joint of each specimen were randomly divided into experimental group (anatomic locking plate fixation) and control group (oblique T shape locking plate fixation). The sternoclavicular joint activity and common force mechanism was simulated on the universal mechanical testing machine, and the clavicular distal load test, sternoclavicular joint torsion test, and anti-pulling of steel plate manubrium part test were performed. Results: The differences between the anatomical parameters of gross measurement and CT measurement were not significant ( P>0.05). In the clavicular distal load test, when the anatomical position perpendicular to the distal clavicle back loading to 20 N, the displacement of loading point in the experimental group was (8.455±0.981) mm, which was significantly less than that in control group [(10.163±1.379) mm] ( t=-3.012, P=0.020); the distal clavicle displacement of loading point of experimental group and control group were (5.427±1.154) mm and (6.393±1.040) mm, respectively, showing no significant difference ( t=-1.459, P=0.188)。In the sternoclavicular joint torsion test, the torque of experimental group was significantly greater than that of control group when the clockwise torsion angle was at 2, 4, 6, 8, and 10 degrees and the counterclockwise torsion angle was at 4, 6, 8, and 10 degrees ( P<0.05). The torsional stiffness in the experimental group under clockwise and counterclockwise condition was 0.122 and 0.108 N·m/° respectively, which were significantly higher than those in the control group (0.083 and 0.078 N·m/° respectively) ( F=67.824, P=0.000; F=20.992, P=0.002). In the anti-pulling of steel plate manubrium part test, the maximum pullout force of experimental group [(225.24±16.02) N] was significantly higher than that in control group [(174.40±21.90) N] ( t=5.785, P=0.001). Conclusion: The new type of anatomical locking plate can realize the sternoclavicular joint three-dimensional fixation, and has the advantages of reliable fixation, simple operation, less trauma, superior biomechanical properties, and earlier functional exercise. It may be an ideal internal fixation device in clinical treatment of sternoclavicular joint dislocation or peripheral fractures.

Effects of NOB1 on the pathogenesis of osteosarcoma and its expression on the chemosensitivity to cisplatin.

The effects of NIN1/RPN12 binding protein 1 homolog (NOB1) on the pathogenesis of osteosarcoma and its expression on the chemosensitivity to cisplatin were investigated. Seventy-four patients with osteosarcoma who received surgical resection in The Affiliated Hospital of Southwest Medical University (Sichuan, China) from September 2013 to September 2016 were enrolled in this study. The expression of NOB1 in cancer and cancer-adjacent tissues of patients was detected by reverse transcription-polymerase chain reaction, and the relationship between NOB1 expression and the pathogenesis of osteosarcoma was analyzed. The expression of NOB1 in osteosarcoma MG-63 cells was interfered with using small interfering ribonucleic acid (siRNA). Western blotting was used to detect the transfection efficiency and changes in apoptosis indicators. Cell Counting Kit-8 (CCK-8) assay was used to examine changes in the sensitivity of cells to cisplatin. The effect of NOB1 knockout on cell apoptosis was examined by flow cytometry. In patients with osteosarcoma, the level of NOB1 mRNA in cancer tissues was significantly higher than that in cancer-adjacent tissues (p<0.05), and the expression of NOB1 was correlated with Ennecking staging and tumor size (p<0.05). The expression level of the apoptotic indicator caspase-3 was activated after siRNA interfered with NOB1 expression, thus reducing the expression level of anti-apoptotic indicator B-cell lymphoma 2. CCK-8 results showed that the downregulation of NOB1 increased the sensitivity of MG-63 cells to cisplatin (p<0.05). In addition, flow cytometry showed that the downregulation of NOB1 significantly promoted the apoptosis of MG-63 cells. NOB1 is significantly upregulated in patients with osteosarcoma, thus reducing the curative effect of cisplatin chemotherapy, which indicates that the prognosis is poor.

Sparstolonin B prevents lumbar intervertebral disc degeneration through toll like receptor 4, NADPH oxidase activation and the protein kinase B signaling pathway.

Intervertebral disc degeneration (IVDD) is the most common pathogeny of lumbago. It is the pathological basis for a series of spinal degenerative diseases. For a long time, the diagnosis and treatment of lumbago have rendered difficult, since the pathogeny has not been identified. Therefore, the present study aimed to investigate the protective effect of Sparstolonin B in preventing lumbar intervertebral disc degeneration, and explored its potential mechanism in rats. Firstly, Sparstolonin B effectively reduced the histological score of disc degeneration and increased endplate porosity of L2 superior endplates in a lumbar IVDD rat model. Sparstolonin B significantly inhibited the IVDD­induced inflammatory factors tumor necrosis factor­α, interleukin (IL)­1ß and IL­6, oxidative stress factors (malondialdehyde), and superoxide dismutase and caspase­3/9 activities. Treatment with Sparstolonin B significantly suppressed toll­like receptor 4 (TLR4), myeloid differentiation primary response protein 88 (MyD88) and nuclear factor (NF)­κB protein expression, inhibited NAPDH oxidase 2 protein expression and induced phosphoinositide 3­kinase and phosphorylated protein kinase B protein expression in the IVDD rat model. These results demonstrated that Sparstolonin B prevents lumbar IVDD­induced inflammation, oxidative stress and apoptosis through TLR4/MyD88/NF­κB, NADPH oxidase activation and the phosphoinositide 3­kinase/protein kinase B signaling pathway. These results implicate Sparstolonin B for use as a therapeutic agent for IVDD in clinical applications.

miR-127-5p promotes chondrogenic differentiation in rat bone marrow mesenchymal stem cells.

The effect and related mechanisms of miR-127-5p on the cartilage differentiation of rat bone marrow mesenchymal stem cells (BMSCs) was investigated. Rat BMSCs were generated and transfected with miR-127-5p, RT-PCR and Safranin O staining were used to detect the effect of miR-127-5p on the cartilage differentiation of rat BMSCs. Western blot analysis was used to detect the related mechanisms of miR-127-5p on the cartilage differentiation of rat BMSCs. Genes related to cartilage differentiation such as Sox9, collagen II and aggrecan were significantly increased in the group which were transfected with miR-127-5p, while collagen X, which was related to cartilage hypertrophy, was decreased in the miR-127-5p transfected group. Safranin O staining revealed that the expression of chondroitin sulfate was significantly increased in the group of miR-127-5p, than the miRNA control group. Western blot analysis showed that miR-127-5p transfection promoted the expression of Sox9, while decreased the expression of Runx2 of rat BMSCs. In conclusion, via increasing the expression of Sox9 and decreasing the expression of Runx2, miR-127-5p could promote cartilage differentiation and decrease cartilage hypertrophy of rat BMSCs.

Initiation of Targeted Nanodrug Delivery in Vivo by a Multifunctional Magnetic Implant.

Implant-mediated targeted drug delivery without an external magnetic field is very challenging. In this work, we report targeted nanodrug delivery initiated by a Fe3O4/poly(lactic-co-glycolic acid) implant scaffold with high magnetism. The implant scaffold is biocompatible and durable. It effectively attracts nanodrugs to its surface, thus killing cancer cells. These findings provide a proof of concept for the magnetic implant-directed nanodrug targeting without the need for an external magnetic field. This approach may further facilitate more precise medical treatments.

[Development and clinical application of a new type of intramedullary nail tail cap].

Objective: To develop a new type of tail cap for closing the tail of the central hole of the interlocking intramedullary nail so as to reduce difficulty in implantation of the tail cap into intramedullary nail, and ensure the accuracy of implantation, as well as reduce unnecessary operation time. Methods: In 2014, the new type of intramedullary nail tail cap ("new tail cap" for short) was successfully developed, and has been granted national utility model patent. A randomized controlled clinical trial was conducted in 34 patients with non pathological femoral shaft fractures treated between August 2014 and March 2016. The patients were randomly divided into groups A and B, 17 patients each group. There was no significant difference in gender, age, side, body mass index, cause of injury, injury to operation time, and fracture AO classification between groups ( P>0.05), with comparability. All patients underwent fixation with interlocking intramedullary nail, and the new tail cap and original tail cap were used in groups A and B respectively. The blood loss and operation time during tail cap implantation, fracture healing time, and complications were recorded and compared between 2 groups; the limb function was evaluated by Klemm function evaluation standard. Results: The blood loss and operation time during tail cap implantation of group A [(3.5±0.8) mL and (10.57±3.15) s] were significantly less than those of group B [(5.5±1.7) mL and (21.99±6.90) s] ( t=-8.281, P=0.010; t=-10.743, P=0.009). All new tail caps were successfully implanted by one-time in group A, and the one-time success rate was 100%; the original tail cap exfoliation occurred in 3 cases of group B, and the one-time success rate was 82.4%. All the patients were followed up 6-16 months (mean, 9.7 months); there was no deep infection, loosening or breakage of internal fixation, and other serious complications. The time of fracture healing was (16.4±3.2) weeks in group A and (15.8±3.5) weeks in group B, showing no significant difference ( t=0.514, P=0.611). At last follow-up, according to the Klemm function evaluation standard, the results were excellent in 14 cases and good in 3 cases in group A, and were excellent in 11 cases and good in 6 cases in group B, showing no significant difference between 2 groups ( χ2=0.142, P=0.707). Conclusion: The new type of femoral intramedullary nail tail cap can simplify operation, shorten operation time, and reduce blood loss, and it has satisfactory effectiveness.

[EFFECTIVENESS OF DIGITAL CUSTOMIZED STEEL PLATE IN TREATMENT OF COMPLEX FRACTURES OF LIMBS].

OBJECTIVE: To observe the effectiveness of digital customized plate in the treatment of complex limb fracture. METHODS: Between January 2012 and May 2013, CT raw data of complex limb fracture were used to establish the fracture three-dimensional simulation model after reduction, and a customized personalized anatomic plate was designed and used for internal fixation after open reduction in 42 cases. There were 22 males and 20 females, aged 16-53 years (average, 37.4 years). The causes of injury were traffic accident in 21 cases, falling from height in 18 cases, crush by heavy objects in 3 cases, including 26 cases of fresh closed fracture and 16 cases of open fracture (9 cases of type I and 7 cases of type II according to Gustilo classification). According to AO classification, there were 15 cases of humerus comminuted fracture, 4 cases of radial comminuted fracture, 8 cases of femoral comminuted fracture, and 15 cases of tibia comminuted fracture. The interval of injury and operation was 6-28 days (mean, 10 days). RESULTS: Reduction and internal fixation of fracture were successfully performed on 42 patients. The length and position of digital customized plate, direction and length of screw implant, number of screw were basically identical with preoperative design. The operation time was 35-120 minutes (mean, 70 minutes); the blood loss volume was 30-500 mL (mean, 180 mL); and X ray fluoroscopy frequency was 2-6 times (mean, 3 times). Superficial infection occurred in 2 cases, and was cured after dressing change; primary healing of incision was obtained in the other patients. Forty-two cases were followed up 6-24 months with an average of 11.5 months. The fracture healing time was 8-19 weeks (mean, 14 weeks) in 41 cases; delayed union occurred in 1 case at 44 weeks after operation. The fracture anatomical reduction was achieved in 19 cases, malunion in 3 cases, and functional reduction in the other patients. At last follow-up, no plate and screw loosening and breakage was observed. CONCLUSION: Digital customized plate in treatment of complex fractures of limbs, especially for the multiple comminuted fracture of long bones of the limbs has the advantages of convenient operation, less trauma, fewer complications, and good effectiveness.