Dual-functional thermosensitive hydrogel for reducing infection and enhancing bone regeneration in infected bone defects.

The contamination of bone defects is a serious therapeutic problem. The treatment of infected bone defects involves rigorous infection control followed by bone reconstruction. Considering these two processes, the development of biomaterials possessing antibacterial and osteogenic properties offers a promising approach for the treatment of infected bone defects. In this study, a dual-functional, thermosensitive, and injectable hydrogel composed of chitosan (CS), quaternized CS (QCS), and nano-hydroxyapatite (nHA) was designed, and the ratio of CS to QCS in the hydrogel was optimized to enhance the antibacterial efficacy of CS while reducing the cytotoxicity of QCS. In vitro studies demonstrated that the hydrogel with an 85 %:15 % ratio of CS to QCS exhibited excellent biocompatibility and antibacterial properties while also possessing suitable mechanical characteristics and degradability. The incorporation of nHA into the hydrogel enhanced MC3T3-E1 proliferation and osteogenic differentiation. Moreover, this hydrogel demonstrated superior in vivo therapeutic effectiveness in a rabbit model of infected bone defect. In summary, this study provides a promising material design and a comprehensive one-step treatment strategy for infected bone defects.

Engineered three-dimensional bioactive scaffold for enhanced bone regeneration through modulating transplanted adipose derived mesenchymal stem cell and stimulating angiogenesis.

Titanium alloy materials are commonly used in orthopedic clinical treatments. However, conventional titanium implants usually lead to insufficient bone regeneration and integration because of mismatched biomechanics and poor bioactivities. To tackle these challenges, a porous titanium alloy scaffold with suitable mechanical properties was prepared using three-dimensional (3D) printing, and then an adipose-derived mesenchymal stem cell (ADSC) loaded platelet-rich plasma (PRP) gel was placed into the pores of the porous scaffold to construct a bioactive scaffold with dual functions of enhancing angiogenesis and osteogenesis. This bioactive scaffold showed good biocompatibility and supported cell viability proliferation and morphology of encapsulated ADSCs. Osteogenic and angiogenic growth factors in the PRP gel promoted the migration and angiogenesis of human umbilical vein endothelial cells (HUVECs) in vitro and enhanced osteogenic-related gene and protein expression in ADSCs, thus promoting osteogenic differentiation. After implantation into the femoral defects of rabbits, the bioactive scaffold promoted vascular network formation and the expression of osteogenesis-related proteins, thus effectively accelerating bone regeneration. Therefore, the osteogenic and angiogenic bioactive scaffold comprising a 3D printed porous titanium alloy scaffold, PRP, and ADSCs provides a promising design for orthopedic biomaterials with clinical transformation prospects and an effective strategy for bone defect treatment.

A Novel Navigation Device for Precise Percutaneous Placement of the Guidewire in Femoral Neck Fracture Cannulated Screw Fixation Surgery.

The accuracy of screw placement is a key factor for the stability of the cannulated screws used in the fixation of femoral neck fractures. In this study we designed a navigation device for ensuring the screw reaches the ideal position for optimal fixation. From March 2019 to September 2020, 66 patients with femoral neck fracture were enrolled and divided into 2 groups, one group was treated using the traditional free-hand cannulated screw fixation and the other using the new navigation device with assisted fixation. The effectiveness of the 2 methods was compared based on surgery duration, intraoperative bleeding, number of fluoroscopic examination and guidewire insertion attempts, screw parallelism, and effective fixation area. Fracture healing, complications and hip joint function were assessed after operation. The new navigation device reduced the duration of surgery without causing additional intraoperative bleeding, and significantly reduced number of fluoroscopy examination and guidewire insertion attempts (4.00±1.58 vs. 6.09±1.94 with traditional surgery). The accuracy of screw implantation was improved, as demonstrated by increased screw parallelism (0.71±0.57° vs. 1.66 ±1.01° with traditional surgery) and higher effective fixed area (64.88±10.52 vs. 58.61±9.19 mm2 with traditional surgery). In the postoperative follow-up, except for one case of femoral head necrosis and one case of bone nonunion in the traditional surgical group, the other patients showed fracture healing. There was no significant difference in hip joint function between the 2 groups. The new navigation device enables rapid and accurate guidewire positioning for cannulated screw fixation through simple operation procedures, resulting in good prospect for clinical transformation.

Surgical flip-dislocation of the bicolumnar approach without olecranon osteotomy versus olecranon osteotomy in type AO 13C3 distal humeral fracture: a matched-cohort study.

BACKGROUND: Our experience with the surgical flip-dislocation of the bicolumnar (SFDB) approach for type AO 13C3 humeral fractures indicates that this surgical approach can be performed safely and effectively in appropriately selected patients. We aimed to evaluate the clinical outcomes of the SFDB approach without olecranon osteotomy (OO) for type AO 13C3 distal humeral fractures. METHODS: We retrospectively reviewed 65 cases of type AO 13C3 distal humeral fractures treated between April 2008 and July 2018; 33 patients were treated with the SFDB approach, and the remaining were treated with OO. Propensity score matching was used to control for sex, age, and the American Society of Anesthesiology score. Elbow pain, range of motion, stability, and function were assessed using the Mayo Elbow Performance Index (MEPI) and the Disabilities of the Arm, Shoulder, and Hand questionnaire. Clinical complications, reoperation rates, and radiographic results were compared between the groups. RESULTS: Operative time and blood loss were significantly lower in the SFDB group than in the OO group (P = 0.001, P = 0.002, respectively). At the final follow-up, the mean postoperative MEPI did not significantly differ between the groups (P = 0.628). According to Morrey's criteria, a typical functional range of elbow motion was achieved in 12 and 15 patients in the SFDB and OO groups, respectively. CONCLUSIONS: The SFDB approach achieves superior exposure of the articular surface without injury to the extensor mechanism in type 13C3 articular surface fracture treatment. This approach also results in good early functional recovery and clinical outcomes, with a low risk of complications.

Functionalized Decellularized Bone Matrix Promotes Bone Regeneration by Releasing Osteogenic Peptides.

The decellularized bone matrix (DCB) provides a promising bone substitute for the treatment of bone defects because of its similar biochemical, biophysical, and mechanical properties to normal bone tissue. However, the decellularized procedure also greatly reduced its osteogenic induction activity. In this study, peptides derived from the knuckle epitope of bone morphogenetic protein-2 were incorporated into the thermo-sensitive hydrogel poloxamer 407, and the peptide-loaded hydrogel was then filled into the pores of DCB to construct a functionalized scaffold with enhanced osteogenesis. In vitro studies have shown that the functionalized DCB scaffold possessed appropriate mechanical properties and biocompatibility and exhibited a sustained release profile of osteogenic peptide. These performances critically facilitated cell proliferation and cell spreading of bone marrow mesenchymal stem cells and upregulated the expression of osteogenic-related genes by activating the Smad/Runx2 signaling pathway, thereby promoting osteogenic differentiation and extracellular matrix mineralization. Further in vivo studies demonstrated that the functionalized DCB scaffold accelerated the repair of critical radial defects in rabbits without inducing excessive graft-related inflammatory responses. These results suggest a clinically meaningful strategy for the treatment of large segmental bone defects, and the prepared osteogenic peptide modified composite DCB scaffold has great application potential for bone regeneration.

Antibacterial peptides-loaded bioactive materials for the treatment of bone infection.

Bacterial bone infection in open fractures is an urgent problem to solve in orthopedics. Antimicrobial peptides (AMPs), as a part of innate immune defense, have good biocompatibility. Their antibacterial mechanism and therapeutic application against bacteria have been widely studied. Compared with traditional antibiotics, AMPs do not easily cause bacterial resistance and can be a reliable substitute for antibiotics in the future. Therefore, various physical and chemical strategies have been developed for the combined application of AMPs and bioactive materials to infected sites, which are conducive to maintaining the local stability of AMPs, reducing many complications, and facilitating bone infection resolution. This review explored the molecular structure, function, and direct and indirect antibacterial mechanisms of AMPs, introduced two important AMPs (LL-37 and ß-defensins) in bone tissues, and reviewed advanced AMP loading strategies and different bioactive materials. Finally, the latest progress and future development of AMPs-loaded bioactive materials for the promotion of bone infection repair were discussed. This study provided a theoretical basis and application strategy for the treatment of bone infection with AMP-loaded bioactive materials.

Drug delivery systems based on polyethylene glycol hydrogels for enhanced bone regeneration.

Drug delivery systems composed of osteogenic substances and biological materials are of great significance in enhancing bone regeneration, and appropriate biological carriers are the cornerstone for their construction. Polyethylene glycol (PEG) is favored in bone tissue engineering due to its good biocompatibility and hydrophilicity. When combined with other substances, the physicochemical properties of PEG-based hydrogels fully meet the requirements of drug delivery carriers. Therefore, this paper reviews the application of PEG-based hydrogels in the treatment of bone defects. The advantages and disadvantages of PEG as a carrier are analyzed, and various modification methods of PEG hydrogels are summarized. On this basis, the application of PEG-based hydrogel drug delivery systems in promoting bone regeneration in recent years is summarized. Finally, the shortcomings and future developments of PEG-based hydrogel drug delivery systems are discussed. This review provides a theoretical basis and fabrication strategy for the application of PEG-based composite drug delivery systems in local bone defects.

Reverse-traction skin-stretching device for primary closure of large skin defects.

The tension in the skin margin of a wound is the major determinant for wound healing. The difficulty of primary closure for large skin defects due to excessive wound tension has long been a clinical challenge. In this study, we designed and fabricated a reverse-traction skin-stretching device (RT-SSD) to relieve the skin tension of a large skin defect and thereby allow primary wound closure. The novel RT-SSD designed in this study drives the fixing device fixed on the skin edge of the wound by rotating the pulling device, thus exerting a reverse tensile force on both sides of the wound, causing creep and stress relaxation, thus reducing the skin tension. Through the tension analyses; microcirculation detection; clinical scores; and a series of histological staining in vivo, it is verified that intraoperative application of RT-SSD can stretch and straighten collagen and fragment elastin, thus effectively reducing skin tension of large skin defect of miniature pigs. In addition, its special linear and planar traction protects the subcutaneous microcirculation of the wound site. The evaluation of wound healing confirmed that RT-SSD had negligible negative impact on wounds, reduced the incidence of complications, and promoted the healing of large skin defects. Therefore, this study provides a new safe and effective device for the primary closure of large skin defects.

[Corrigendum] Gene silencing of NOB1 by lentivirus suppresses growth and migration of human osteosarcoma cells.

Subsequently to the publication of this paper, an interested reader drew to the authors' attention that, on p. 2174 in the Materials and methods section (subsection "Lentivirus production and lentiviral transduction"), the sequence presented for the shRNA targeting the gene NOB1 appeared to conform with the sequence that would have been predicted to target PNO1, according to a blastn search. The authors have checked their original paper, and realize that the sequence of this shRNA was written incorrectly in the paper; the sequence for the shRNA targeting the gene NOB1 should have been written as: GCTTGCACTCACATACCAGTTCTCGAG- AACTGGTATGTGAGTGCAAGC. Furthermore, the published version of Fig. 5A on p. 2178 contained a pair of overlapping panels, such that data were apparently derived from the same original source even though they were intended to show the results from differently performed experiments. After having re­examined their original data, the authors have realized that a pair of data panels were inadvertently incorporated into this figure incorrectly; specifically, the centre panel of the Lv­shCon group and the right­hand panel of the Lv­shNOB1 group. The revised version of Fig. 5, showing the correct images for the abovementioned pair of data panels in Fig. 5A, is shown opposite. Note that these errors did not significantly affect either the results or the conclusions reported in this paper, and all the authors agree to this corrigendum. Furthermore, the authors thank the Editor of Molecular Medicine Reports for allowing them the opportunity to publish this corrigendum, and apologize to the readership for any inconvenience caused. [Molecular Medicine Reports 9: 2173­2179, 2014; DOI: 10.3892/mmr.2014.2119].

Reconstruction of the coronoid process with the olecranon tip for chronic elbow dislocation in children: A rare case report and literature review.

The coronoid process of the ulna, as a key part of the elbow joint, plays an important role in maintaining elbow joint stability. Reconstruction of the coronoid process is necessary in both acute and chronic coronoid defects to restore elbow stability and avoid early joint degeneration. The olecranon tip may be a useful autologous osteochondral graft for reconstructing the same shape of the ulna coronoid process. The purpose of this report was to verify if reconstruction of the coronoid process with the olecranon tip can restore elbow stability and kinematics. Here, we report a 13-year-old boy who had undergone Kirschner-wire fixation for a left supracondylar fracture of the left humerus 9 years previously. After that, the right elbow dislocation and varus deformity gradually appeared. Imaging revealed posterolateral dislocation of the left elbow due to the absence of the coronoid process of the ulna. We reconstructed the ulnar coronoid process by intercepting the ipsilateral olecranon tip. After 22 months of follow-up, the range of motion of the left elbow joint was normal, and the cubitus varus deformity disappeared. The results of this report suggest that olecranon tip autografts are suitable to replace transverse coronoid defects. Given the patient's satisfactory clinical results, this reconstruction technique is safe and effective for the treatment of chronic elbow instability due to coronoid process defects of the ulna.

The use of the pediatric physeal slide-traction plate in the treatment of neer-horwitz grade IV proximal humeral fractures in children: A case report and literature review.

Background: Proximal humeral fractures (PHFs) are rare in children. Currently, the recommended surgical methods for severely displaced PHFs are closed reduction and percutaneous fixation using K-wires or intramedullary nailing, which can't provide firm internal fixation, especially for older and high-weight children. This study aimed to introduce a novel surgical approach, pediatric physeal slide-traction plate fixation (PPSP), for Neer-Horwitz grade IV PHFs in children. Case summary: A 9-year-old boy presented with left shoulder pain and swelling due to a car accident. Physical examination revealed a positive shoulder deformity and local tenderness. On physical examination, we palpated bone friction without vascular and nerve damage. Based on imaging findings, we diagnosed Neer-Horwitz grade IV PHF. In view of the patient's condition, we performed PPSP after careful communication with the patient's parents. After 22 months of follow-up, the patient's left shoulder function was satisfactory, and there was no restriction of activities. Conclusion: According to previous studies, PPSP is only used for femur fractures. To the best of our knowledge, this is the first in the treatment for PHFs. Given the satisfactory outcomes, it is a safe and effective method and may provide a reference to cure analogous patients in the future.

MicroRNA-loaded biomaterials for osteogenesis.

The large incidence of bone defects in clinical practice increases not only the demand for advanced bone transplantation techniques but also the development of bone substitute materials. A variety of emerging bone tissue engineering materials with osteogenic induction ability are promising strategies for the design of bone substitutes. MicroRNAs (miRNAs) are a class of non-coding RNAs that regulate intracellular protein expression by targeting the non-coding region of mRNA3'-UTR to play an important role in osteogenic differentiation. Several miRNA preparations have been used to promote the osteogenic differentiation of stem cells. Therefore, multiple functional bone tissue engineering materials using miRNA as an osteogenic factor have been developed and confirmed to have critical efficacy in promoting bone repair. In this review, osteogenic intracellular signaling pathways mediated by miRNAs are introduced in detail to provide a clear understanding for future clinical treatment. We summarized the biomaterials loaded with exogenous cells engineered by miRNAs and biomaterials directly carrying miRNAs acting on endogenous stem cells and discussed their advantages and disadvantages, providing a feasible method for promoting bone regeneration. Finally, we summarized the current research deficiencies and future research directions of the miRNA-functionalized scaffold. This review provides a summary of a variety of advanced miRNA delivery system design strategies that enhance bone regeneration.

Novel Covert-Inferior Pelvic Approach with a Subpubic Plate for Anterior Pelvic Ring Fractures: Preliminary Results.

BACKGROUND: Anterior pelvic ring injuries can be treated via Pfannenstiel, modified Stoppa, or ilioinguinal approaches, but these require exposing the abdominal soft tissues and may damage pelvic organs. The scar on the abdominal wall is also unacceptable for some patients. The minimally invasive anterior pelvic ring internal fixator (INFIX) is not ideal for thin patients with easily irritated skin, and it is associated with complications such as femoral nerve palsy, vascular occlusion, and lateral femoral cutaneous nerve injury. In this study, we designed a new external pelvic approach for the treatment of an anterior pelvic ring fracture. METHODS: We retrospectively reviewed 28 patients with 36 pubic ramus fractures that had been treated via the covert-inferior pelvic approach. All patients underwent a surgical procedure between August 2019 and January 2021. According to the Nakatani classification, there were 6 cases of type-I fracture, 25 cases of type-II fracture, and 5 cases of type-III fracture. Operative time, blood loss, and postoperative radiographic and computed tomographic (CT) findings were recorded. Patients were followed for fracture healing time, functional status, esthetic satisfaction, and complications. RESULTS: A total of 27 patients had follow-up for at least 12 months (range, 12 to 29 months). Postoperative radiographs and CT scans showed well-positioned plates and screws. The mean preoperative time was 9.4 ± 3.8 days, the mean operative time was 61.3 ± 22.67 minutes, the mean intraoperative blood loss was 63.6 ± 42.62 mL, the mean fracture healing time was 4.1 ± 1.6 months, and the mean Majeed score was 89.74 ± 8.07. There were no complications of nonunion, internal fixation failure, vascular injury, nerve palsy, or hernia. All of the patients were esthetically satisfied with the scar. CONCLUSIONS: The covert-inferior pelvic approach combined with a subpubic plate effectively fixed Nakatani type-I, II, and III fractures. The advantages of this method include rapid recovery after the surgical procedure, safety, simplicity, a short learning curve, no damage to abdominal soft tissue, no effect on pubic symphysis micromotion, and esthetic benefits. It may be another option for anterior pelvic ring fractures and can supplement other approaches. LEVEL OF EVIDENCE: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.

Thermosensitive vancomycin@PLGA-PEG-PLGA/HA hydrogel as an all-in-one treatment for osteomyelitis.

Osteomyelitis is a difficult-to-treat infectious disease. Treatment, which includes controlling the infection and removing necrotic tissues, is challenging. Considering the side effects and drug resistance of systemic antibiotics, local drug delivery systems are being explored. Antibiotic-loaded bone cement is the main treatment strategy; however, it has several disadvantages. Thus, based on its thermosensitive gelation properties, poly(D, L-lactide-co-glycolide)-poly(ethylene glycol)-poly(D, L-lactide-co-glycolide) (PLGA-PEG-PLGA) copolymer was used as a sustained-release drug carrier by calibrating its synthesis parameters. We prepared and characterized vancomycin@PLGA-PEG-PLGA/hydroxyapatite (HA) thermosensitive hydrogel with an LA/GA ratio of 15:1. The rheological characteristics, sol-gel phase-transition properties, and critical micelle concentration value of the PLGA-PEG-PLGA/HA complex confirmed that it undergoes a temperature-sensitive sol-gel phase transition. Furthermore, the HA in the composite increased the storage modulus of the system. FT-IR, XRD, and TEM findings showed that HA could be dispersed uniformly in the PLGA-PEG-PLGA polymer. Moreover, HA neutralized acidity during polymer degradation, improving in vitro cytocompatibility. In vitro and in vivo antibacterial experiments showed that the composite sustained-release system exhibited good bone repair characteristics owing to its efficacy in infection treatment. Therefore, vancomycin@PLGA-PEG-PLGA/HA allows sustained release of antibiotics and promotes bone tissue repair, showing potential for wide clinical applicability.

Dual-functional composite scaffolds for inhibiting infection and promoting bone regeneration.

The treatment of infected bone defects is an intractable problem in orthopedics. It comprises two critical parts, namely that of infection control and bone defect repair. According to these two core tasks during treatment, the ideal approach of simultaneously controlling infection and repairing bone defects is promising treatment strategy. Several engineered biomaterials and drug delivery systems with dual functions of anti-bacterial action and ostogenesis-promotion have been developed and demonstrated excellent therapeutic effects. Compared with the conventional treatment method, the dual-functional composite scaffold can provide one-stage treatment avoiding multiple surgeries, thereby remarkably simplifying the treatment process and reducing the treatment time, overcoming the disadvantages of conventional bone transplantation. In this review, the impaired bone repair ability and its specific mechanisms in the microenvironment of pathogen infection and excessive inflammation were analyzed, providing a theoretical basis for the treatment of infectious bone defects. Furthermore, we discussed the composite dual-functional scaffold composed of a combination of antibacterial and osteogenic material. Finally, a series of advanced drug delivery systems with antibacterial and bone-promoting capabilities were summarized and discussed. This review provides a comprehensive understanding for the microenvironment of infectious bone defects and leading-edge design strategies for the antibacterial and bone-promoting dual-function scaffold, thus providing clinically significant treatment methods for infectious bone defects.

Chitosan-Based Biomaterial Scaffolds for the Repair of Infected Bone Defects.

The treatment of infected bone defects includes infection control and repair of the bone defect. The development of biomaterials with anti-infection and osteogenic ability provides a promising strategy for the repair of infected bone defects. Owing to its antibacterial properties, chitosan (an emerging natural polymer) has been widely studied in bone tissue engineering. Moreover, it has been shown that chitosan promotes the adhesion and proliferation of osteoblast-related cells, and can serve as an ideal carrier for bone-promoting substances. In this review, the specific molecular mechanisms underlying the antibacterial effects of chitosan and its ability to promote bone repair are discussed. Furthermore, the properties of several kinds of functionalized chitosan are analyzed and compared with those of pure chitosan. The latest research on the combination of chitosan with different types of functionalized materials and biomolecules for the treatment of infected bone defects is also summarized. Finally, the current shortcomings of chitosan-based biomaterials for the treatment of infected bone defects and future research directions are discussed. This review provides a theoretical basis and advanced design strategies for the use of chitosan-based biomaterials in the treatment of infected bone defects.

Minimally invasive plate osteosynthesis for complex comminuted bone fractures in the Fraser's type II floating knee: a case report.

OBJECTIVE: Floating knee type IIC, according to Fraser's classification, is an uncommon severe injury that typically occurs in polytrauma. In such cases, intra-articular fracture and the high degree of comminution and deformity of the mid-distal femur make fixation challenging. The purpose of this study was to demonstrate that minimally invasive plate osteosynthesis (MIPO) technology can simplify these complex problems and improve patient prognosis. CASE PRESENTATION: A 38-year-old man injured his left leg in a car accident, causing pain, swelling, deformity, and limited mobility on his left knee and thigh, and two small open wounds were noted mainly of the anterior aspect of the mid-distal thigh. Physical examination and computed tomography angiography of the lower limb confirmed that there was no damage to the neurovascular system. The clinical diagnosis was closed intra-articular fracture of the proximal tibia, open intra-articular fracture of the distal femur with extension to the diaphysis, and a patellar fracture on the ipsilateral knee. The treatment strategy involved a locking plate system applying MIPO technology. Postoperative evaluation of the patient was satisfactory, with immediate functional exercise, full weight-bearing after three months, and return to daily activity without pain. Final follow-up taken 3 years after surgery showed good lower limb alignment and complete plasticity of the bone structure, by which time the patient showed good limb function. CONCLUSIONS: Minimally invasive techniques can provide a simple and effective treatment for some complex fractures.

Plasma Fluorescent Oxidation Products and Bone Mineral Density Among Male Veterans: A Cross-Sectional Study.

In vitro and vivo studies indicate that oxidative stress contributes to bone loss. Fluorescent oxidation products (FlOPs) are novel biomarkers of oxidative stress; they reflect global oxidative damage of lipids, proteins, carbohydrates, and DNA. However, whether FlOPs are associated with bone mineral density (BMD) is still unclear. In the present study, we examined the association between FlOPs and BMD among male veterans. This cross-sectional study was conducted among participants recruited from the Department of Medical Examination, The Second Hospital of Jilin University in Jilin, China. We identified male veterans who were at least 50 y old between June and October of 2019. Plasma FlOPs were measured with a fluorescent microplate reader (excitation/emission wavelength: 320/420 nm). BMD were measured by dual-energy X-ray absorptiometry (DXA). The association between FlOPs and BMD was tested by multivariable linear regression models. A total of 164 male veterans were enrolled in the study, the average age was 56.6 y. After adjusting for covariates, veterans who had FlOP levels in the highest tertile had a statistically significant lower femoral neck (ß = -0.044; p = 0.007) and total hip BMD (ß = -0.045; p = 0.020) as compared to those with FlOP levels in the lowest tertile. Similar results were found when FlOPs were treated as a continuous variable (per 1-SD increase, ß = -0.014 and p = 0.033 for femoral neck BMD; ß = -0.016 and p = 0.047 for total hip BMD). Higher FlOP levels were associated with lower BMD among male veterans.

Identification of serum exosomal miR-98-5p, miR-183-5p, miR-323-3p and miR-19b-3p as potential biomarkers for glioblastoma patients and investigation of their mechanisms.

BACKGROUND: Exosomal miRNAs have attracted increasing interest as potential biomarkers and treatment targets for cancers, however, glioblastoma (GBM)-related exosomal miRNAs remain rarely reported. The study aimed to screen crucial serum exosomal miRNAs in GBM patients and explored their possible mechanisms. METHODS: Serum exosomal miRNA profile datasets of GBM patients and normal controls were downloaded from the Gene Expression Omnibus database (GSE112462 and GSE122488). The differentially expressed miRNAs (DEMs) were identified using the limma method. Their diagnostic values were assessed by receiver operating characteristic (ROC) curve analysis. The target genes of DEMs were predicted by the miRwalk 2.0 database. Function enrichment analysis was performed using the DAVID database. The expression and prognosis of target genes were validated using TCGA sequencing data and immunohistochemistry. RESULTS: Seven DEMs were shared in two datasets, among which hsa-miR-183-5p and hsa-miR-98-5p as well as has-miR-323-3p or has-miR-19b-3p constituted a diagnostic signature to distinguish GBM from controls, with the area under the ROC curve nearly approximate to 1. MAPK8IP1/FAM175B, OSMR/CASP3, PTPN2 and FBXO32 may be underlying targets for hsa-miR-183-5p, hsa-miR-98-5p, has-miR-323-3p and has-miR-19b-3p, respectively. Function analysis showed all of these target genes were involved in cell proliferation and related signaling pathways [positive regulation of cell proliferation (OSMR), negative regulation of transcription from RNA polymerase II promoter (PTPN2), cell division (FAM175B), regulation of transcription, DNA-templated (MAPK8IP1), hsa05200:Pathways in cancer (CASP3) and hsa04068:FoxO signaling pathway (FBXO32)]. The protein and (or mRNA) expression levels of OSMR, CASP3, PTPN2 and FBXO32 were validated to be upregulated, while MAPK8IP1 and FAM175B were downregulated in GBM tissues. Also, OSMR, CASP3, PTPN2 and FBXO32 were associated with patients' prognosis. CONCLUSION: These findings suggest these four exosomal miRNAs may represent potential diagnostic biomarkers and therapeutic targets for GBM.

First case of forearm crisscross injury in children: A case report.

BACKGROUND: Forearm crisscross injury is rare in children; there is no relevant literature so far. Surgeons lack experience and knowledge in treating this type of crisscross injury. We report a case of forearm crisscross injury in a child for the first time and analyze its mechanism. CASE SUMMARY: An 8-year-old boy experienced pain in his left forearm when he accidentally fell while skateboarding. Physical examination revealed swelling and deformity of the left forearm. We performed imaging and the results revealed left radial head dislocation, left distal radial epiphyseal separation from the shaft, and interruption of the continuity of the dorsal cortex of the left distal ulna. Anteroposterior and lateral X-ray films showed that the radius and ulna were crisscrossed. A diagnosis of superior radioulnar joint dislocation, left distal radial epiphyseal injury, and left distal ulnar fracture was made. After unsuccessful manual reduction, we adopted a minimally invasive procedure and succeeded. After a 14-wk period of follow-up, the patient had good left upper limb function, no complaints of pain or limited range of motion, and good follow-up results. CONCLUSION: This is the first report of a child with a forearm crisscross injury in which the mechanism and the differences from adult crisscross injury are analyzed. Minimally invasive surgery with intramedullary fixation can achieve a good therapeutic effect. This case provides a reference for the treatment of similar patients in the future.