Exploration of the miR-187-3p/CNR2 pathway in modulating osteoblast differentiation and treating postmenopausal osteoporosis through mechanical stress.

This study aimed to explore how mechanical stress affects osteogenic differentiation via the miR-187-3p/CNR2 pathway. To conduct this study, 24 female C57BL/6 mice, aged 8 weeks, were used and divided into four groups. The Sham and OVX groups did not undergo treadmill exercise, while the Sham + EX and OVX + EX groups received a 8-week treadmill exercise. Post-training, bone marrow and fresh femur samples were collected for further analysis. Molecular biology analysis, histomorphology analysis, and micro-CT analysis were conducted on these samples. Moreover, primary osteoblasts were cultured under osteogenic conditions and divided into GM group and CTS group. The cells in the CTS group underwent a sinusoidal stretching regimen for either 3 or 7 days. The expression of early osteoblast markers (Runx2, OPN, and ALP) was measured to assess differentiation. The study findings revealed that mechanical stress has a regulatory impact on osteoblast differentiation. The expression of miR-187-3p was observed to decrease, facilitating osteogenic differentiation, while the expression of CNR2 increased significantly. These observations suggest that mechanical stress, miR-187-3p, and CNR2 play crucial roles in regulating osteogenic differentiation. Both in vivo and in vitro experiments have confirmed that mechanical stress downregulates miR-187-3p and upregulates CNR2, which leads to the restoration of distal femoral bone mass and enhancement of osteoblast differentiation. Therefore, mechanical stress promotes osteoblasts, resulting in improved osteoporosis through the miR-187-3p/CNR2 signaling pathway. These findings have broad prospect and provide molecular biology guidance for the basic research and clinical application of exercise in the prevention and treatment of PMOP.

Unprecedented non-hysteretic superelasticity of [001]-oriented NiCoFeGa single crystals.

Superelasticity associated with the martensitic transformation has found a broad range of engineering applications1,2. However, the intrinsic hysteresis3 and temperature sensitivity4 of the first-order phase transformation significantly hinder the usage of smart metallic components in many critical areas. Here, we report a large superelasticity up to 15.2% strain in [001]-oriented NiCoFeGa single crystals, exhibiting non-hysteretic mechanical responses, a small temperature dependence and high-energy-storage capability and cyclic stability over a wide temperature and composition range. In situ synchrotron X-ray diffraction measurements show that the superelasticity is correlated with a stress-induced continuous variation of lattice parameter accompanied by structural fluctuation. Neutron diffraction and electron microscopy observations reveal an unprecedented microstructure consisting of atomic-level entanglement of ordered and disordered crystal structures, which can be manipulated to tune the superelasticity. The discovery of the large elasticity related to the entangled structure paves the way for exploiting elastic strain engineering and development of related functional materials.

Unraveling submicron-scale mechanical heterogeneity by three-dimensional X-ray microdiffraction.

Shear banding is a ubiquitous phenomenon of severe plastic deformation, and damage accumulation in shear bands often results in the catastrophic failure of a material. Despite extensive studies, the microscopic mechanisms of strain localization and deformation damage in shear bands remain elusive due to their spatial-temporal complexities embedded in bulk materials. Here we conducted synchrotron-based X-ray microdiffraction (µXRD) experiments to map out the 3D lattice strain field with a submicron resolution around fatigue shear bands in a stainless steel. Both in situ and postmortem µXRD results revealed large lattice strain gradients at intersections of the primary and secondary shear bands. Such strain gradients resulted in severe mechanical heterogeneities across the fatigue shear bands, leading to reduced fatigue limits in the high-cycle regime. The ability to spatially quantify the localized strain gradients with submicron resolution through µXRD opens opportunities for understanding the microscopic mechanisms of damage and failure in bulk materials.

Negative effects of high mechanical tensile strain stimulation on chondrocyte injury in vitro.

The mechanism underlying the development of osteoarthritis induced by high tensile strain is unclear. In this study, the effects of different degrees of mechanical tensile strain stimulation on Sprague-Dawley rat chondrocytes were explored. Rat chondrocytes were subjected to mechanical tensile strain at different intensities and frequencies (control group, low tensile strain group, intermediate tensile strain group, and high tensile strain group) using a self-made in vitro tensile strain device. After applying mechanical tensile strain, chondrocytes were collected to detect the expression of collagen II, Aggrecan, matrix metalloproteinase 13 (MMP13), ADAMTS5, and uncoupling protein 2 (UCP2) by real-time quantitative PCR and western blotting as well as reactive oxygen species (ROS) by fluorescence probes. Mechanical tensile strain at different frequencies and intensities had different effects on the biological functions of chondrocytes. Compared with the control group, the expression levels of Col II and Aggrecan in the low and intermediate tensile strain groups increased significantly, while the expression of MMP13 and ADAMTS5 decreased. There were no significant differences between the low and intermediate tensile strain groups. Col II and Aggrecan levels were significantly lower in the high tensile strain group than in the control group, while MMP13 and ADAMTS5 levels were higher. There were no significant differences in ROS production between the low and intermediate tensile strain groups and the control group, but the high tensile strain group exhibited significantly increased ROS production. The expression of UCP2 was significantly lower in the high tensile strain group than in all other groups. These results showed that stimulation with different levels of mechanical tensile strain has different effects on chondrocytes. Repeated high tensile strain promoted the anabolic function of chondrocytes, increased ROS production, and decreased UCP2. These results provide a potential mechanism by which osteoarthritis is induced by high mechanical tensile strain.

A novel navigation template for fixation of acetabular posterior column fractures with antegrade lag screws: design and application.

PURPOSE: To test whether a novel guide template we designed can facilitate accurate insertion of antegrade lag screws in the fixation of acetabular posterior column fractures. METHODS: We created virtual three-dimensional reconstruction models of the pelvis from CT scan data obtained from 96 adult patients without any bony problems. A virtual cylindrical implant was placed along the longitudinal axis of the acetabular posterior column passing through the ischial tuberosity. The diameter of cylindrical implant was augmented to 6.5 mm, and the direction was adjusted until the optimal screw path was found using the reverse engineering technique. The orifice of this cylinder from the iliac fossa was determined as the entry point for the antegrade lag screw. The anatomical parameters of the screw entry path were measured and saved in .stl format. The guide template was designed according to the acetabular morphology and the measured anatomical parameters before it was put into manufacture of a solid template with the rapid prototyping technique. The feasibility and accuracy of the guide template were tested in cadaveric pelvises. Finally, the guide template was used in real surgery for five patients. Furthermore, the time required for surgery was recorded. RESULTS: Under the guide of this navigation template, antegrade lag screws were successfully placed in the posterior column of the acetabulum in the cadaveric test. And five lag screws were successfully placed in five patients. The mean time of antegrade lag screw insertion required 5.8 (3-10) min. CONCLUSIONS: Antegrade lag screws can be more accurately put into the posterior column of the acetabulum with the help of this navigation template.

Strong-Yet-Ductile Eutectic Alloys Employing Cocoon-Like Nanometer-Sized Dislocation Cells.

Eutectic alloys (EAs) with superior fluidity are known to be the easiest to cast into high-quality ingots, making them the alloys of choice for making large-sized structural parts. However, conventional EAs (CEAs) have never reached strength-ductility combinations on par with the best in other alloy categories. Via thermomechanical processing of cast Ni-32.88wt%Fe-9.53wt%Al CEAs, a cocoon-like nano-meshed (as fine as 26 nm) network of dislocations (CNN-D) is produced via recovery annealing, through the rearrangement of cold-work-accumulated dislocations anchored by dense pre-existing nanoprecipitates. In lieu of traditional plasticity mechanisms, such as TWIP and TRIP, the CNN-D is particularly effective in eutectic lamellae with alternating phases, as it instigates nanometer-spaced planar slip bands that not only dynamically refine the microstructure but also transmit from the FCC (face-centered-cubic) layers into the otherwise brittle B2 layers. These additional mechanisms for strengthening and strain hardening sustain stable tensile flow, resulting in a striking elevation of both strength and ductility to outrank not only all previous CEAs, but also the state of the art-additively manufactured eutectic high-entropy alloys. The CNN-D thus adds a novel microstructural strategy for performance enhancement, especially for compositionally complex alloys that increasingly make use of nanoprecipitates or local chemical order.

Free flap transplantation combined with skin grafting and vacuum sealing drainage for repair of circumferential or sub-circumferential soft-tissue wounds of the lower leg.

BACKGROUND: This study is aimed at evaluating the operation techniques and clinical significance of free flap transplantation combined with skin grafting and vacuum sealing drainage (VSD) in repairing severe traumatic extensive circumferential or semi-circumferential soft-tissue defects of the lower leg. MATERIAL AND METHODS: Thirty patients with severe lower leg injuries were treated by free flap transplantation combined with skin grafting and VSD from January 2008 to June 2011. The size of the wounds ranged from 23×8 cm to 44×28 cm and all affected more 70% of the low leg circumferential area. Wounds were complicated by exposure, necrosis, or infection of deep tissues. The wounds were first debrided and covered by VSD. When the condition of the wound had improved (5 to 7 days later), free flaps were harvested to reconstruct damaged tissue and skin grafts and VSD was used to cover granulation tissues around the transplanted flap. RESULTS: Granulation tissues developed and the area requiring flap cover decreased in all 30 patients after debridement and VSD. In 28 of 30 cases, the transplanted flaps grew well without complication. Peripheral necrosis was observed in only 2 cases, which required a second debridement and skin graft. Ten wound areas covered by grafts were left with scattered peripheral wounds, which healed with the help of 1 more skin graft or dressing change. Morphological appearance and functional recovery were satisfactory in all 30 cases. CONCLUSIONS: Initial debridement and the temporary VSD cover followed after several days by free flap transplantation combined with skin grafting and VSD protection is a reliable treatment regimen for traumatic large circumferential or sub-circumferential soft tissue wounds of the lower leg with deep tissue exposure.

Arthroscopically-assisted reduction and fixation of an old osteochondral fracture of the lateral femoral condyle.

BACKGROUND: Osteochondral fracture (OCF) of the lateral femoral condyle has a low incidence and old OCF is even more rarely seen; it is difficult to differentiate from late osteochondritis dissecans (OCD). CASE REPORT: In this report, we present the case of a 20-year-old male patient with an old OCF of the lateral femoral condyle. The possible etiology of OCF is discussed, along with its clinical manifestation, diagnosis, and treatment. He underwent arthroscopically-assisted reduction and fixation with cannulated screws. Four months after the surgery, arthroscopy showed good osteochondral healing, and screws were removed. He had achieved good functional recovery by the follow-up visit. CONCLUSIONS: Old OCF should be distinguished from OCD in clinical practice, and osteochondral bodies should be preserved as much as possible. Osteochondral reduction and fixation under arthroscopy was minimal and the clinical effect was good.

[Treatment of large circular soft tissue defect in lower extremities with a combination of bridge flaps and free skin graft covered by vacuum sealing drainage].

OBJECTIVE: To explore the surgical technique and clinical value of treatment for posttraumatic large circular soft tissue defect in the lower extremities using a combination of posterior tibial vascular bridge flap in the unaffected leg and skin graft covered by vacuum sealing drainage (VSD). METHODS: From January 2008 to June 2010, 11 cases with posttraumatic large circular soft tissue defects with deep tissue exposed or partial necrosis in the lower extremities were treated by bridge flaps and combined with free skin graft covered by VSD. There are 7 males and 4 females, with an average age of 32.5 years (range from 15 to 52 years). The size of wound varied from 24 cm × 13 cm to 45 cm × 24 cm. After the wound were completely debrided, the external fixation or internal fixation was conducted for the patients with unstable fracture. Then VSD were used to covered the wound for 1-2 times with a period of 5 to 7 days according to the wound condition. After granulation tissue grew, bridge flap transplantation was performed to repair tissue defect and cover the exposed bone, which combined with skin graft covered by VSD was used to cover the residual wound. Survival rate and quality healing of the flaps were followed up postoperatively. RESULTS: The granulation growth of 11 cases with large circular soft tissue defect in the lower extremities associated tissue exposure was good after the application of VSD. All the cases were covered by free flap transplantation and skin grafting except for 6 cases due to large defect. The wound was covered by skin re-grafting in 4 cases and frequently dressing change in 2 cases. All the flaps were successful with good infection control and no sinus. The average period of follow-up was 10.6 months (5 - 24 months). All the patients were satisfied with the good outline and good function of the affected limb. CONCLUSION: Patients with posttraumatic large circular soft tissue defect in the lower extremities can be effectively treated with a combination of bridge flaps and free skin graft covered by VSD, which can shorten the course of treatment, and restore the function of affected extremities as much as possible.

Retrospective Analysis of Infection Factors in Secondary Internal Fixation after External Fixation for Open Fracture of a Long Bone: A Cohort of 117 Patients in a Two-Center Clinical Study.

Purpose: To investigate infection risk factors after secondary internal fixation (IF) of open fracture of a long bone with removed fixation frame and explore the safe range of feasible operation for abnormal inflammatory indicators. Methods: Clinical data of 117 cases of open fracture of a long bone that underwent temporary external fixation (EF) in one stage and IF in two stages were retrospectively analyzed. Collected data included age, sex, Gustilo type, multiple injuries, debridement time, duration of EF, needle infection, interval of conversion to IF after external fixator, preoperative white blood cell (WBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), albumin (ALB), blood glucose, and prognosis. We selected these factors for univariate analysis of postoperative surgical site infection (SSI) and multivariate logistic regression analysis of statistically significant risk factors and created receiver operating characteristic (ROC) curves to compare the diagnostic efficiency of each index and determine the optimal screening point. Results: We followed up 117 patients, with 130 limbs affected. Univariate analysis showed that ESR, CRP, ALB, WBC, EF time, and Gustilo fracture type were significantly associated with SSI. Multivariate logistic regression analysis showed that CRP, duration of EF, and Gustilo fracture type were independently associated with postoperative infection. Area under ROC curves for WBC, ESR, and CRP were 69.7%, 73.2%, and 81.2%. Conclusions: We demonstrated the role of Gustilo classification of open fractures in predicting postoperative infection, especially for open fractures above type III. If the inflammatory indexes return to normal or show a downward trend, and the second-stage IF operation is performed within the cutoff values, postoperative recurrent infection was reduced.

PM2.5 induced lung injury through upregulating ROS-dependent NLRP3 Inflammasome-Mediated Pyroptosis.

The main cause of air pollution is PM2.5, which directly causes lung injury through respiration. Oxidative stress and inflammation are considered to be the key mechanism of cell damage. Pyroptosis is a process of the programmed death of inflammatory cells and as a dangerous endogenous signal, it is widely involved in different inflammatory diseases. However, few studies have been conducted on PM2.5 exposure and cell pyroptosis. In this study, we aimed to investigate the effect of PM2.5 on apoptosis, pyroptosis and cell cycle arrest regulated by reactive oxygen species production. Balb/c mice were exposed to PM2.5 dynamically and verified by the RAW264.7 cells in vitro. The results showed the activation of NF-κB and NLRP3 inflammasome and the release of IL-1ß and reactive oxygen species were caused by exposure to PM2.5. The maturation of IL-1ß relied on Caspase-1, and the active Caspase-1 was related to cell pyroptosis. Oxidative stress, inflammation, apoptosis and pyroptosis all affected the cell cycle. This study describes a potentially important mechanism of PM2.5-induced lung damage that PM2.5 promotes lung injury via upregulating ROS-NLRP3-mediated the RAW264.7 cells pyroptosis.

Reconstruction of coronoid process of the ulna: a literature review.

As a pivotal part of the elbow joint structure, the coronoid process of the ulna plays a vital role in maintaining elbow joint stability. Loss of coronoid process height causes instability of the elbow joint depending on the fracture characteristics and size. The diagnosis and treatment of coronoid process fractures has gained widespread attention from orthopedic surgeons. Nevertheless, few reports have described reconstruction of coronoid process fractures and defects that affect elbow joint stability. Treatment of elbow joint instability induced by coronoid process defects is challenging because most cases are complicated by other elbow joint injuries. Moreover, the clinical efficacy remains unclear. The present narrative review was performed to examine the research progress on reconstruction of the coronoid process. The findings of this review provide evidence for clinical repair and reconstruction of coronoid process defects and contribute to the published literature on this topic.

Emergency amputation necessitated within 24 hours by a human bite: a case report.

We herein review and analyze the diagnosis, treatment, and outcome of a severe infection caused by a human bite. A 68-year-old man was bitten on the forearm by a 3-year-old child. Rapid progression of infection, severe local and systemic poisoning, and diverse clinical manifestations were observed at presentation. Based on the medical history, physical signs, imaging examinations (X-ray films, color Doppler ultrasound, and computed tomography), laboratory examinations, and multidisciplinary consultation, the patient was diagnosed with gas gangrene or gas gangrene-like changes. Twenty-four hours after the injury, an emergency amputation was performed (open amputation with wound closure after 1 week). After the operation, the patient was sent to the intensive care unit for isolation and further anti-infection and anti-shock treatments. His condition gradually improved after treatment and he was discharged without further complications. Bacteriological and pathological examinations indicated Aeromonas hydrophila infection leading to extensive necrotizing fasciitis of the limb and severe systemic poisoning. In addition, pre-existing myelodysplastic syndrome progressing to acute myeloid leukemia was identified as a possible predisposing factor. Human bites can cause serious infections requiring timely treatment, particularly in patients with predisposing comorbidities.

Knockdown of MCM8 functions as a strategy to inhibit the development and progression of osteosarcoma through regulating CTGF.

Osteosarcoma is the most common primary malignant tumor of bone derived from osteoblasts, which is a noteworthy threat to the health of children and adolescents. In this study, we found that MCM8 has significantly higher expression level in osteosarcoma tissues in comparison with normal tissues, which was also correlated with more advanced tumor grade and pathological stage. In agreement with the role of MCM proteins as indicators of cell proliferation, knockdown/overexpression of MCM8 inhibited/promoted osteosarcoma cell proliferation in vitro and tumor growth in vivo. Also, MCM8 knockdown/overexpression was also significantly associated with the promotion/inhibition of cell apoptosis and suppression/promotion of cell migration. More importantly, mechanistic study identified CTGF as a potential downstream target of MCM8, silencing of which could enhance the regulatory effects of MCM8 knockdown and alleviate the effects of MCM8 overexpression on osteosarcoma development. In summary, MCM8/CTGF axis was revealed as critical participant in the development and progression of osteosarcoma and MCM8 may be a promising therapeutic target for osteosarcoma treatment.

Tensile strain promotes osteogenic differentiation of bone marrow mesenchymal stem cells through upregulating lncRNA-MEG3.

BACKGROUND: With the aging of the population, osteoporosis is becoming more and more common. This progressive bone disease increases the risk of fractures and pain and causes serious harm to people's health and quality of life. Several studies, including our previous studies, confirmed that tensile strain can promote bone marrow mesenchymal stem cell (BMSC) osteogenic differentiation in vitro. In this study, we further explored the mechanism by which tensile strain regulates BMSC differentiation. METHODS: A device designed by our group was used to apply tensile strain to BMSCs to study the effects of tensile strain on their differentiation. LncRNA-MEG3 overexpression and silencing models of BMSCs were constructed by lentivirus transfection to study the involvement of lncRNA-MEG3. We assessed osteogenic differentiation of BMSCs by alkaline phosphatase (ALP) staining and the expression of Runx2 mRNA and BMP2 mRNA, while adipogenic differentiation was evaluated by oil red staining and the expression of PPARγ mRNA and C/EBPα mRNA. RESULTS: We demonstrated that proper tensile strain can promote osteogenic differentiation of BMSCs while inhibiting differentiation into adipocytes, and simultaneously promote the expression of lncRNA-MEG3. The overexpression of lncRNA-MEG3 further promotes osteogenic differentiation of stressed BMSCs and inhibits expression of miR-140-5p; the knockdown of lncRNA-MEG3 induces the opposite effects. CONCLUSION: Appropriate mechanical stimulation can inhibit the expression of miR-140-5p by promoting lncRNA-MEG3 expression, thereby promoting the osteogenic differentiation of BMSCs. Our results provide a theoretical basis for physical exercise to improve the prevention and treatment of osteoporosis.

Free flap transplantation combined with Ilizarov bone transport for the treatment of severe composite tibial and soft tissue defects.

OBJECTIVE: To evaluate the clinical efficacy of free flap transplantation combined with Ilizarov bone transport in the treatment of severe composite tibial and soft tissue defects. METHODS: We retrospectively analyzed the clinical data of 40 patients with severe composite tibial and soft tissue defects who underwent free flap transplantation combined with Ilizarov bone transport. The clinical efficacy was evaluated according to the following criteria: success rate of wound repair by free flap transplantation, incidence or recurrence rate of deep infection, healing rate of bone defects and external fixation index, incidence of complications, and functional score of affected extremities. RESULTS: All infections were generally well controlled by radical debridement and negative-pressure therapy, and all 40 patients' wounds healed after repair and reconstruction of the tibia and soft tissues. Postoperative complications were alleviated by active treatment. The mean external fixation time was 12.83 ± 2.85 months, and the external fixation index was 1.55 m/cm. According to the Association for the Study and Application of Methods of Ilizarov (ASAMI) score, an excellent or good functional outcome was attained in 85% of patients. CONCLUSION: Free flap transplantation combined with Ilizarov bone transport is an effective treatment for severe composite tibial and soft tissue defects.

Study on the relationship between the timing of conversion from external fixation to internal fixation and infection in the treatment of open fractures of extremities.

OBJECTIVE: To investigate the relationship between the infection rate and the timing of replacement of temporary external fixators with internal fixation, and the timing of immediate or delayed internal fixation after removal of temporary external fixation in the staging treatment modality of open fractures of extremities. METHODS: A retrospective analysis was performed on 122 cases of open fractures of extremities. External fixators were applied at the early stage and replaced with internal fixation when the condition of soft tissues improved and inflammatory indexes dropped to the normal range or showed a steady downward trend. Depending on the carrying time of external fixators after wound closure or healing, the patients were divided into three groups; the carrying time of groups A, B, and C was ≤ 14 days, 15-28 days, and > 28 days, respectively. Depending on the immediate or delayed internal fixation after removal of external fixator, patients were divided into group a (immediate internal fixation after removal of external fixator) and group b (delayed internal fixation after removal of external fixator, 5-7 days later). RESULTS: The infection rates of groups A, B, and C were 6.5%, 5.9%, and 23.3%, respectively. The differences among the three groups were statistically significant (P < 0.05). The infection rates of different Gustilo-Anderson fractures were as follows: no cases of infection out of 10 cases with type I fracture (0%); two cases of infection out of 35 cases with type II fracture (5.7%); three cases of infection out of 36 cases with IIIa fracture (8.3%); five cases of infection out of 28 cases with IIIB fracture (17.9%); and five cases of infection out of 13 cases with IIIC fracture (38.5%). The differences among the five groups were statistically significant. CONCLUSIONS: The occurrence of infection of open fractures of extremities is associated with the fracture severity (Gustilo classification). For open fractures of Gustilo types I and II, the final internal fixation should be placed as soon as possible when the recovery of general and local conditions is good and the infection is controlled.

PAX8-AS1 knockdown facilitates cell growth and inactivates autophagy in osteoblasts via the miR-1252-5p/GNB1 axis in osteoporosis.

Osteoporosis (OP) is the most common systematic bone disorder among elderly individuals worldwide. Long noncoding RNAs (lncRNAs) are involved in biological processes in various human diseases. It has been previously revealed that PAX8 antisense RNA 1 (PAX8-AS1) is upregulated in OP. However, its molecular mechanism in OP remains unclear. Therefore, we specifically designed this study to determine the specific role of PAX8-AS1 in OP. We first established a rat model of OP and then detected PAX8-AS1 expression in the rats with RT-qPCR. Next, to explore the biological function of PAX8-AS1 in osteoblasts, in vitro experiments, such as Cell Counting Kit-8 (CCK-8) assays, flow cytometry, western blotting and immunofluorescence (IF) staining, were conducted. Subsequently, we performed bioinformatic analysis and luciferase reporter assays to predict and identify the relationships between microRNA 1252-5p (miR-1252-5p) and both PAX8-AS1 and G protein subunit beta 1 (GNB1). Additionally, rescue assays in osteoblasts clarified the regulatory network of the PAX8-AS1/miR-1252-5p/GNB1 axis. Finally, in vivo loss-of-function studies verified the role of PAX8-AS1 in OP progression. The results illustrated that PAX8-AS1 was upregulated in the proximal tibia of OP rats. PAX8-AS1 silencing promoted the viability and inhibited the apoptosis and autophagy of osteoblasts. PAX8-AS1 interacted with miR-1252-5p. GNB1 was negatively regulated by miR-1252-5p. In addition, the impacts of PAX8-AS1 knockdown on osteoblasts were counteracted by GNB1 overexpression. PAX8-AS1 depletion suppressed OP progression by inhibiting apoptosis and autophagy in osteoblasts. In summary, PAX8-AS1 suppressed the viability and activated the autophagy of osteoblasts via the miR-1252-5p/GNB1 axis in OP.

Reconstruction of Large Area of Deep Wound in the Foot and Ankle with Chimeric Anterolateral Thigh Perforator Flap.

OBJECTIVE: To evaluate the clinical application and surgical efficacy of the chimeric perforator flap pedicled with the descending branch of the lateral circumflex femoral artery and the lateral thigh muscle flap for the reconstruction of the large area of deep wound in foot and ankle. METHODS: Clinical data of 32 cases who underwent chimeric anterolateral thigh perforator flap to repair the large area of deep wound of the foot and ankle from January 2015 to December 2018 were retrospectively analyzed. The sizes of the defects ranged from 18 cm × 10 cm to 35 cm × 20 cm, with exposed tendon and bone and/or partial defects and necrosis, contaminations, accompanied by different degrees of infection. Following the radical debridement and VSD, chimeric anterolateral thigh perforator flap was employed to repair the deep wounds according to the position, site and deep-tissue injury of the soft-tissue defects. The skin flap and muscle flap were fanned out on the wound, and single- or two-staged split-thickness skin grafting was performed on the muscle flap. The operation time and blood loss were recorded. The survival and healing conditions of the operational site with chimeric anterolateral thigh perforator flap were evaluated post-operationally. Complications at both recipient site and donor site were carefully recorded. RESULTS: The mean time of the operation was 325.5 min and average blood loss was 424.8 mL. Among the 32 cases, two cases developed vascular crisis, which were alleviated with intensive investigation and treatment; Four cases suffered from partial necrosis of the flap or skin graft on the muscle flap or on the residual local wound, which were improved after treatment of further dressing change and skin grafting. Another four cases experienced post-traumatic osteomyelitis accompanied by bone defect were treated with simple bone grafting or Mesquelet bone grafting at 6-8 months after wound healing. Postoperatively, the wounds were properly healed, and the infection was effectively controlled without sinus tract forming. Overall, all 32 cases received satisfactory efficacy, without influencing subsequent functional reconstruction, and observed infection during the 12-36 months post-operational follow-up. CONCLUSION: The chimeric perforator flap pedicled with the descending branch of the lateral circumflex femoral artery and the lateral thigh muscle flap provides an effective and relative safe procedure for the repair of a large area of deep wound in the foot and ankle, particularly with irregular defect or deep dead space.

Next­generation sequencing of miRNAs and lncRNAs from rat femur and tibia under mechanical stress.

Exercise intervention has become one of the most effective methods to prevent and treat osteoporosis, which is a common age­related disease and seriously affects the health and quality of life of the elderly. However, the molecular mechanism remains to be elucidated. The present study demonstrated the exercise­induced promotion of osteogenic differentiation and inhibition of adipogenic differentiation in femur and tibia by establishing an animal exercise model using a treadmill exercise system. MicroRNA (miRNA/miR) and long non­coding (lnc)RNA sequencing analyses identified 16 upregulated and two downregulated miRNAs in the exercise group, as well as 44 upregulated lncRNAs and 39 downregulated lncRNAs in the exercise group. There was increased expression of miR­9942 and miR­7704 in both the femur and tibia and an upregulation of miR­30d, miR­5100 and miR­1260 in the femur of animals from the exercise group. In addition, four of the five most downregulated lncRNAs, including lncRNA MSTRG.2625, lncRNA MSTRG.1557, lncRNA MSTRG.691 and lncRNA MSTRG.7497, were demonstrated to be suppressed in both the femur and tibia after treadmill exercise. The results of the present study provided a valuable resource for further exploring the molecular mechanisms underlying the regulation of osteoporosis by exercise.