Redirecting Tumor Evolution with Nanocompiler Precision for Enhanced Therapeutic Outcomes.

Precisely programming the highly plastic tumor expression profile to render it devoid of drug resistance and metastatic potential presents immense challenges. Here, a transformative nanocompiler designed to reprogram and stabilize the mutable state of tumor cells is introduced. This nanocompiler features a trio of components: 2-deoxy-d-glucose-modified lipid nanoparticles to inhibit glucose uptake, iron oxide nanoparticles to induce oxidative stress, and a deubiquitinase inhibitor to block adaptive protein profile changes in tumor cells. By specifically targeting the hypermetabolic nature of tumors, this approach disrupted their energy production, ultimately fostering a state of vulnerability and impeding their ability to adapt and resist. The results of this study indicate a substantial reduction in tumor growth and metastasis, thus demonstrating the potential of this strategy to manipulate tumor protein expression and fate. This proactive nanocompiler approach promises to steer cancer therapy toward more effective and lasting outcomes.

Hybrid Bioactive Hydrogel Promotes Liver Regeneration through the Activation of Kupffer Cells and ECM Remodeling After Partial Hepatectomy.

Partial hepatectomy is an essential surgical technique used to treat advanced liver diseases such as liver tumors, as well as for performing liver transplants from living donors. However, postoperative complications such as bleeding, abdominal adhesions, wound infections, and inadequate liver regeneration pose significant challenges and increase morbidity and mortality rates. A self-repairing mixed hydrogel (O5H2/Cu2+/SCCK), containing stem cell derived cytokine (SCCK) derived from human umbilical cord mesenchymal stem cells (HUMSCs) treated with the traditional Chinese remedy Tanshinone IIA (TSA), is developed. This SCCK, in conjunction with O5H2, demonstrates remarkable effects on Kupffer cell activation and extracellular matrix (ECM) remodeling. This leads to the secretion of critical growth factors promoting enhanced proliferation of hepatocytes and endothelial cells, thereby facilitating liver regeneration and repair after partial hepatectomy. Furthermore, the hydrogel, featuring macrophage-regulating properties, effectively mitigates inflammation and oxidative stress damage in the incision area, creating an optimal environment for postoperative liver regeneration. The injectability and strong adhesion of the hydrogel enables rapid hemostasis at the incision site, while its physical barrier function prevents postoperative abdominal adhesions. Furthermore, the hydrogel's incorporation of Cu2+ provides comprehensive antibacterial effects, protecting against a wide range of bacteria types and reducing the chances of infections after surgery.

Increased lower limb length ratio in patients with patellar instability.

PURPOSE: Patellar height is a risk factor for patellar instability, correlated with the tibia length/femur length (T/F) ratio. This study aimed to explore the changes in the T/F ratio in patients with patella instability and the potential correlation with the morphology of the patellofemoral joint and extensor moment arm. METHOD: A retrospective analysis was performed to assess the ratio of lower limb length morphological characteristics of the patellofemoral by full weight-bearing long-leg standing radiographs, magnetic resonance imaging, and computed tomography in 75 patients with patellar instability and 75 participants from a randomly selected control group from January 2020 to September 2021. A total of eight parts were measured, including mechanical tibia length/femur length (mT/F) ratio, anatomical tibia length/femur length (aT/F) ratio, hip-knee-ankle angle, femoral neck-shaft angle, femoral valgus cut angle, patellar height, Dejour classification, sulcus angle, trochlear angle, medial trochlear inclination, lateral trochlear inclination, patella tilt angle and patellar tendon moment arm to evaluate the difference of morphology between patient group and control groups. RESULTS: The mT/F (0.840 ± 0.031 vs. 0.812 ± 0.026, p < 0.001) and aT/F (0.841 ± 0.033 vs. 0.808 ± 0.028, p < 0.001) ratios in the patient group were significantly greater than that in the control group. There was a significant correlation between patellar height and increased mT/F and aT/F ratios (p < 0.05). CONCLUSION: Patients with patellar instability had a larger lower limb length ratio, and the change in lower limb length ratio was correlated with patellar height.

BMSC-Derived Exosomes Inhibit Dexamethasone-Induced Muscle Atrophy via the miR-486-5p/FoxO1 Axis.

Sarcopenia, characterized by reduced muscle function as well as muscle mass, has been a public health problem with increasing prevalence. It might result from aging, injury, hormone imbalance and other catabolic conditions. Recently, exosomes were considered to regulate muscle regeneration and protein synthesis. In order to confirm the effect of BMSC-derived exosomes (BMSC-Exos) on muscle, dexamethasone-induced muscle atrophy was built both in vitro and in vivo. In the present research, BMSC-Exos attenuated the decrease of myotube diameter induced by dexamethasone, indicating that BMSC-Exos played a protective role in skeletal muscle atrophy. Further mechanism analysis exhibited that the content of miR-486-5p in C2C12 myotubes was up-regulated after treated with BMSC-Exos. Meanwhile, BMSC-Exos markedly downregulated the nuclear translocation of FoxO1, which plays an important role in muscle differentiation and atrophy. Importantly, the miR-486-5p inhibitor reversed the decreased expression of FoxO1 induced by BMSC-Exos. In animal experiments, BMSC-Exos inhibited dexamethasone-induced muscle atrophy, and miR-486-5p inhibitor reversed the protective effect of BMSC-Exos. These results indicating that BMSC-derived exosomes inhibit dexamethasone-induced muscle atrophy via miR486-5p/Foxo1 Axis.

LncRNA ORLNC1 Promotes Bone Marrow Mesenchyml Stem Cell Pyroptosis Induced by Advanced Glycation End Production by Targeting miR-200b-3p/Foxo3 Pathway.

Bone marrow mesenchymal stem cells (BMSCs) are a type of adult stem cells that originate from the mesoderm and have important roles in the body because of their self-renewal and multidirectional differentiation potential. Now it has been proved that BMSCs are closely related to the development of osteoporosis (OP). There is growing evidence that lncRNAs are involved in regulating the pyroptosis of BMSCs. And advanced glycation end-products (AGEs) have been recognized as NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome activators. In this study, we aimed to explore the role of lncRNA ORLNC1 (NONMMUT016106.2) on the pyroptosis of BMSCs under CML (Nε-(carboxymethyl) lysine, the most common AGEs) treatment and its specific molecular mechanisms. Our study revealed that CML treatment promoted pyroptosis of BMSCs and upregulated ORLNC1 expression. As a competing endogenous RNA (ceRNA) of miR-200b-3p, the level of ORLNC1 was negatively correlated with miR-200b-3p. Foxo3 was a target of miR-200b-3p and ORLNC1 promoted BMSCs pyroptosis induced by CML through targeting miR-200b-3p/Foxo3 pathway.

Exosomes Derived From M2 Macrophages Facilitate Osteogenesis and Reduce Adipogenesis of BMSCs.

Bone regeneration is a complex process that requires the coordination of osteogenesis and osteoclastogenesis. The balance between osteogenesis and adipogenesis of bone marrow mesenchymal stem cells (BMSCs) plays a major role in the process of bone formation. Recently, intercellular communication between bone cells and surrounding cells has been gradually recognized, and macrophages on the surface of bone have been proven to regulate bone metabolism. However, the underlying mechanisms have not been fully elucidated. Recent studies have indicated that exosomes are vital messengers for cell-cell communication in various biological processes. In this experiment, we found that exosomes derived from M2 macrophages (M2D-Exos) could inhibit adipogenesis and promote osteogenesis of BMSCs. M2D-Exo intervention increased the expression of miR-690, IRS-1, and TAZ in BMSCs. Additionally, miR-690 knockdown in M2 macrophages with a miR-690 inhibitor partially counteracted the effect of M2D-Exos on BMSC differentiation and the upregulation of IRS-1 and TAZ expression. Taken together, the results of our study indicate that exosomes isolated from M2 macrophages could facilitate osteogenesis and reduce adipogenesis through the miR-690/IRS-1/TAZ axis and might be a therapeutic tool for bone loss diseases.

Open-Wedge HTO with Absorbable ß-TCP/PLGA Spacer Implantation and Proximal Fibular Osteotomy for Medial Compartmental Knee Osteoarthritis: New Technique Presentation.

PURPOSE: The purpose of this study was to present a new absorbable spacer for medial compartmental knee osteoarthritis (OA). The functional and radiographic results of patients treated with the novel surgical technique were also evaluated to investigate its clinical feasibility. METHODS: Patients with medial compartmental knee OA who underwent open-wedge high tibial osteotomy (HTO) with absorbable ß-TCP/PLGA [30% beta-tricalcium phosphate and 70% poly (lactic-co-glycolic acid)] spacer implantation and proximal fibular osteotomy from January 2016 to February 2017 were retrospectively analyzed. The operation time, blood loss, and relevant complications were reviewed. The femorotibial angle (FTA), varus angle (VA), joint line convergence angle (JLCA), American Knee Society Score (KSS), and visual analog scale (VAS) score were recorded preoperatively and at the final follow-up, respectively. RESULTS: At the final follow-up, the mean FTA and JLCA were 179.85° ± 4.34° and 2.44° ± 1.26°, respectively, which were smaller than the preoperative values (182.94° ± 3.86° and 4.12° ± 1.65°, respectively; both p < 0.001). The final VA and VAS score were lower than those measured preoperatively (both p < 0.001). The clinical and functional KSSs at the final follow-up were higher than the preoperative scores (p < 0.001). CONCLUSIONS: This novel absorbable spacer could provide adequate stability for the tibial osteotomy gap, at a lower cost than a traditional plate. With the use of this spacer as an osteoinductive and biodegradable device, secondary surgery for fixation removal could be avoided. The novel surgical technique could improve both the radiographic appearance and the function of the knee in patients with knee OA.

Liraglutide, a glucagon-like peptide-1 receptor agonist, suppresses osteoclastogenesis through the inhibition of NF-κB and MAPK pathways via GLP-1R.

Bone disorders such as osteoporosis, Paget's disease of the bone, osteogenesis imperfecta, are caused by the uncoordinated action of osteoclasts and osteoblasts. Inhibiting osteoclastogenesis and suppressing the resorptive function of osteoclasts might become a gold standard strategy for treating this kind of disease. Glucagon-like peptide-1 (GLP-1) and its receptor agonist have been reported to have protective effects on bone. Little is known about the effect of GLP-1 on osteoclasts. Therefore, we investigated the effects of liraglutide, a GLP-1 receptor agonist, on murine bone marrow-derived macrophage (BMM) and RAW264.7 preosteoclast differentiation and explored the potential cellular basis of its action. In this study, we confirmed the presence of GLP-1 receptor (GLP-1R) on BMMs and RAW264.7 cells and demonstrated that GLP-1R might be important for osteoclastogenesis by increasing the expression of osteoclastogenic biomarkers after GLP-1R knockdown. In addition, we found that liraglutide treatment of both BMMs and RAW264.7 cells could inhibit osteoclast formation and bone resorption. Mechanistically, Western blotting and RT-PCR showed that liraglutide inhibited the NF-κB and MAPK signalling pathways, ultimately inhibiting the expression of nuclear factor of activated T cells (NFATc1). In addition, knocking down GLP-1R reversed the inhibitory effect of liraglutide on NF-κB/MAPK-NFATc1. Overall, these results indicated a potential therapeutic effect of liraglutide on bone disorders.

Intramedullary nailing versus a locking compression plate for humeral shaft fracture (AO/OTA 12-A and B): A retrospective study.

INTRODUCTION: There has been great progress in surgical techniques for treating humeral shaft fractures over the past few decades. The purpose of this study was to compare the therapeutic effects of intramedullary nailing (IMN) and locking compression plate (LCP) for humeral shaft fractures (AO/OTA 12-A and B). HYPOTHESIS: Compared with LCP, better therapeutic effects could be obtained with less invasive IMN. MATERIALS AND METHODS: Patients with a humeral shaft fracture who received anterograde IMN or LCP fixation in our institution from December 2011 to June 2016 were reviewed in this study. They were divided into two groups according to the different fixation methods: Group A (IMN) and Group B (LCP). The surgical time, intraoperative blood loss, and complications of the patients were reviewed. Fracture healing was evaluated by radiographs performed at each follow-up. The functional outcome was assessed by the DASH (Disabilities of the Arm, Shoulder and Hand) scoring system at the final follow-up. RESULTS: Thirty-four patients in Group A and forty-six patients in Group B were included in this study. Mean incision length and blood loss in Group B were greater than those in Group A (p<0.001). The average surgical times were 118.53minutes in Group A and 128.91minutes in Group B (p=0.114). The mean DASH scores were 23.76±16.78 in Group A and 22.37±15.18 in Group B (p=0.609). The complication rates were 8/34 in Group A and 7/46 in Group B, respectively (p=0.887). DISCUSSION: The study hypothesis was partially confirmed. Although IMN was a less invasive technique, similar therapeutic results were obtained for humeral shaft fractures (AO/OTA 12-A and B) fixed with two surgical methods. LEVELS OF EVIDENCE: III, retrospective comparative study.

Lumbopelvic Fixation Versus Novel Adjustable Plate for Sacral Fractures: A Retrospective Comparative Study.

Purpose: The purpose of this study is to compare the therapeutic effects of the lumbopelvic technique and a novel adjustable plate for sacral fractures. Materials and Methods: Patients with unilateral sacral fractures fixed via the lumbopelvic technique or using a novel adjustable plate from June 2011 to June 2017 were recruited into this study and were divided into two groups: group A (lumbopelvic fixation) and group B (novel adjustable plate). Surgical time, intraoperative blood loss, frequency of intraoperative fluoroscopy, reduction quality, and related complications were reviewed. Fracture healing was assessed by the radiographs conducted at follow-up. Functional outcome was evaluated according to the Majeed score at the final follow-up. Results: The mean blood loss and frequency of intraoperative fluoroscopy in group B were reduced compared with group A (both P < 0.001). The mean surgical time was 122.22 ± 13.09 minutes in group A and 103.96 ± 24.80 minutes in group B (P = 0.007). All patients healed well in this study, and no difference in the fracture healing time was noted between the two groups (P = 0.685). Satisfactory rates of reduction quality and functional outcome did not differ (both P > 0.05) in this study. The complication rate was 22.22% (4/18) in group A and 4.16% (1/24) in group B (P = 0.191). Conclusion: For patients with unilateral sacral fractures, satisfactory radiographic appearance and functional outcome could be obtained by both the lumbopelvic technique and a novel adjustable plate. However, the novel adjustable plate represents a less invasive technique with lower radiograph exposure.

Sacroiliac screw versus a minimally invasive adjustable plate for Zone II sacral fractures: a retrospective study.

OBJECTIVE: Fracture line of the sacrum always involves the Zone II region because sacral foramina are anatomically and physiologically weak regions of the sacrum. The purpose of this study is to compare the therapeutic effects of a sacroiliac screw and a minimally invasive adjustable plate (MIAP) for Zone II sacral fractures. METHODS: Patients with unilateral Zone II sacral fractures fixed with a unilateral sacroiliac screw or MIAP from August 2009 to January 2016 were recruited into this study and were divided into two groups: group A (sacroiliac screw) and group B (MIAP). Surgical time, blood loss, frequency of intraoperative fluoroscopy, and relative complications were reviewed. Radiographs and CT scans were routinely acquired to evaluate the fracture displacement and reduction quality. Fracture healing was evaluated in the radiographs at each follow-up. Functional outcome was assessed based upon the Majeed scoring system at the final follow-up. RESULTS: Thirty-one patients in group A and thirty-nine patients in group B were included in this study. No significant differences in average surgical time (P = 0.221) or blood loss (P = 0.234) were noted between group A and group B. The mean frequency of intraoperative fluoroscopy was 15.74±2.98 in group A and 6.08±1.94 in group B (P = 0.000). All fractures healed well within four months in all patients, and the healing time exhibited no significant difference between the two groups (P = 0.579). Satisfactory rates of reduction quality and functional outcome were not statistically different between the two groups (P > 0.05). The complication rate was 16.13% (5/31) in group A and 5.13% (2/39) in group B (P = 0.222). CONCLUSION: MIAP has a fixation effect and exhibits reduction potential for Zone II sacral fractures. Favourable radiographic and functional results could be obtained through the MIAP technique, which is easy to conduct without pre-contouring. Compared with the unilateral S1 sacroiliac screw technique, repeated projections and iatrogenic sacral injury can be avoided.

Anterior subcutaneous internal fixator (INFIX) versus plate fixation for pelvic anterior ring fracture.

The aim of this study was to compare the clinical outcomes in patients with unstable anterior pelvic ring fractures after treatment with anterior subcutaneous internal fixator (INFIX) or plate fixation. We performed a retrospective study from August 2015 to October 2017. A consecutive series of 74 patients who underwent surgical treatment of their anterior pelvic ring (35 treated with INFIX and 39 treated with plates) were studied. Data collected included patients' demographic data, injury severity score (ISS), AO/OTA classification, injury mechanism, time to surgery, procedure time, and blood loss. The quality of postoperative reduction were assessed by postoperative radiographs using the Tornetta and Matta method. Functional outcome was evaluated using Majeed scoring system. In the INFIX group, ten patients developed LFCN paralysis, one patient suffered from superficial infection. Three screw loosening cases and two wound infection cases occurred in the plate group. INFIX is relatively minimally invasive and time-saving than the reconstruction plate in the treatment of anterior pelvic ring fracture. However, plate fixation increases the rate of anatomic reduction of the pelvic anterior ring fracture. Plates also provide a higher functional outcome compared with INFIX. INFIX is especially suitable in patients with urological injury, which can also decrease the wound infection rate.

Fixation of Displaced Acetabular Fractures With an Anatomic Quadrilateral Surface Plate Through the Stoppa Approach.

Satisfactory fixation for displaced acetabular fractures involving the quadrilateral surface remains difficult to obtain with conventional reconstruction plates. To achieve minimally invasive management of fractures of the quadrilateral surface, the authors designed a type of anatomic quadrilateral surface plate (AQSP). A retrospective study to assess the therapeutic results of the AQSP was performed at their institution. A total of 26 patients with quadrilateral surface fractures fixed with an AQSP through the Stoppa approach from February 2014 to February 2015 were included in this study. There were 16 men and 10 women with a mean age of 37.5 years. The patients were followed for a mean of 28.81 months (range, 24-36 months). The mean operative time was 98.85±16.08 minutes, and the mean intraoperative blood loss was 353.85±124.84 mL. Postoperative radiographs and computed tomography scans showed that anatomic and good reductions were obtained in 88.46% (23 patients) and 11.54% (3 patients) of the patients, respectively. Screw loosening was not observed. All of the fractures healed well at a mean of 3.54 months. Two cases of obturator nerve injury and 1 case of corona mortis rupture were observed. However, permanent complications were not observed. The mean Merle d'Aubigné score at final follow-up was 16.38±1.33 points. The authors conclude that satisfactory fixation with the AQSP system can be achieved through the Stoppa approach. [Orthopedics. 2019; 42(2):e180-e186.].

Minimally invasive treatment for fractures of lower extremity amputees using a rapid reductor.

PURPOSE: A traction table is recommended for lower limb fractures, while it is unavailable for amputees to immobilize the ipsilateral foot to remain stationary and reduce the fracture. For these patients, our rapid reductor can be applied to guarantee stable fixation and optimal reduction, allowing satisfactory implant positioning. This study aims to evaluate the prognosis of amputee patients with lower limb fractures treated by minimally invasive techniques that employ a rapid reductor to reduce the fracture. METHODS: Between 2013 and 2014, 11 cases of amputees suffering from a lower limb fracture were enrolled in the study, including four transtibial amputees with a tibial plateau fracture, three transtibial amputees with a femoral shaft fracture, and four transfemoral amputees with a femoral neck fracture. All fractures involved the amputated ipsilateral lower limbs, which were all reduced in a closed fashion using a rapid reductor. During the operation, the rapid reductor was connected to the injured limb for skeleton traction to reduce the fracture and then used to maintain the reduction for subsequent minimally invasive fixation. The operation time, reduction time, fluoroscopy time, and intra-operative blood loss were recorded. Follow-ups were conducted to evaluate the union of the fractures and the functional recovery. RESULTS: All 11 cases were treated successfully using this minimally invasive technique, with anatomical or nearly anatomical reduction reached in all fractures. The average operative time, reduction time, fluoroscopy time, and intra-operative blood loss were 60 minutes (range, 46-90 minutes), 13.2 minutes (range, 7-20 minutes), 19.8 seconds (range, 6-65 seconds), and 95 mL (range, 80-170 mL), respectively. No incidents of reductor-induced complications occurred during the operation. Patients were followed up for an average of 20.8 months (range, 18-24 months). All fractures healed well on an average of six months. At the latest follow-up, all 11 cases reported satisfactory functional recovery of the fixed limbs, which were similar to that before the fractures. CONCLUSIONS: The rapid reductor can be used to efficiently reduce and maintain ipsilateral fractures of the amputated lower extremity in a closed fashion, which can facilitate minimally invasive fixation of the fractures. The patients can achieve excellent outcomes.

Liraglutide Promotes the Osteogenic Differentiation in MC3T3-E1 Cells via Regulating the Expression of Smad2/3 Through PI3K/Akt and Wnt/ß-Catenin Pathways.

Diabetes is a worldwide health problem with increasing prevalence. Some reports indicate the interplay between bone and glucose metabolism. The imbalance between bone resorption and formation resulted in the structural integrity and strength of bone. Glucagon-like peptide-1 (GLP-1) and its agonists (Liraglutide) have an anabolic action on bone remodeling by stimulating osteoblast differentiation as well as increasing osteoblast longevity. However, the underlying mechanisms remain elusive. We detected the presence of GLP-1 receptor (GLP-1R) in MC3T3-E1 cells via immunocytochemistry assay. Alkaline phosphatase activity assay, alizarin red stain, quantitative real-time polymerase chain reaction, and western blot were employed to detect the effect of Liraglutide on osteogenic differentiation. Liraglutide promoted the expression of GLP-1R in a dosage- and time-dependent manner, and it enhanced the osteogenic differentiation in MC3T3-E1 cells. Liraglutide application improved the levels of Smad2/3 and p-Smad2/3; however, the silencing of Smad2/3 blocked the osteogenic differentiation induced by Liraglutide. What is more, the application of PI3K and Wnt inhibitors inhibited the upregulation of Akt, p-Akt, ß-catenin, Smad2/3, and p-Smad2/3 induced by Liraglutide. Liraglutide facilitated the osteogenic differentiation via the regulation of Smad2/3 via PI3K/AKT and Wnt/ß-catenin pathways. These data revealed a new mechanism of Liraglutide inducing osteogenic differentiation and provided theory evidence to maintain normal bone metabolism during diabetes therapy.

The Hip Morphology Changes with Ageing in Asian Population.

OBJECTIVES: This study aims to determine the changing in hip anatomy parameters with age and reveals the reason for the extorsion of lower extremity in the aged. DESIGN: Retrospective study. PARTICIPANTS: One hundred and forty patients who had received imaging check of the femur and acetabulum between October 2013 and October 2016 were included in this study. MAIN OUTCOME MEASURES: The femoral neck torsion angle (FNTA), neck-shaft angle (NSA), and acetabular anteversion angle (AVA) were measured by an experienced orthopedic surgeon. All the patients' demographic and physical characteristics including age, sex, body laterality, height, and weight were recorded. The Student t-test, two-way ANOVA, Pearson correlation, and multiple linear regression were used for the statistical analysis. RESULTS: The mean age for male and female was 45.01±15.38 and 49.30±17.63 years, respectively. Outcomes revealed that the NSA on the right side of the body, 133.46±4.46° in male and 134.36±4.71° in female, was statistically higher than the left side. Female FNTA had significantly higher values than male (P<0.01). Two-way ANOVA reveals that FNTA and AVA were correlated with age (P<0.05) but not weight, height, or BMI. NSA was correlated with age, weight, and BMI (P<0.05) but not height. Multiple linear regression analysis showed that only age made an independent contribution to NSA. CONCLUSIONS: The NSA and FNTA of Asian population may have an obvious decrease whereas AVA increases with ageing, which reveals the reason for the extorsion of lower extremity with elderly. During hip-related surgery in elderly patients, more attention should be paid to these lower extremity anatomic changes.

Liraglutide Inhibits the Apoptosis of MC3T3-E1 Cells Induced by Serum Deprivation through cAMP/PKA/ß-Catenin and PI3K/AKT/GSK3ß Signaling Pathways.

In recent years, the interest towards the relationship between incretins and bone has been increasing. Previous studies have suggested that glucagon-like peptide-1 (GLP-1) and its receptor agonists exert beneficial anabolic influence on skeletal metabolism, such as promoting proliferation and differentiation of osteoblasts via entero-osseous-axis. However, little is known regarding the effects of GLP-1 on osteoblast apoptosis and the underlying mechanisms involved. Thus, in the present study, we investigated the effects of liraglutide, a glucagon-like peptide-1 receptor agonist, on apoptosis of murine MC3T3-E1 osteoblastic cells. We confirmed the presence of GLP-1 receptor (GLP-1R) in MC3T3-E1 cells. Our data demonstrated that liraglutide inhibited the apoptosis of osteoblastic MC3T3-E1 cells induced by serum deprivation, as detected by Annexin V/PI and Hoechst 33258 staining and ELISA assays. Moreover, liraglutide upregulated Bcl-2 expression and downregulated Bax expression and caspase-3 activity at intermediate concentration (100 nM) for maximum effect. Further study suggested that liraglutide stimulated the phosphorylation of AKT and enhanced cAMP level, along with decreased phosphorylation of GSK3ß, increased ß-catenin phosphorylation at Ser675 site and upregulated nuclear ß-catenin content and transcriptional activity. Pretreatment of cells with the PI3K inhibitor LY294002, PKA inhibitor H89, and siRNAs GLP-1R, ß-catenin abrogated the liraglutide-induced activation of cAMP, AKT, ß-catenin, respectively. In conclusion, these findings illustrate that activation of GLP-1 receptor by liraglutide inhibits the apoptosis of osteoblastic MC3T3-E1 cells induced by serum deprivation through cAMP/PKA/ß-catenin and PI3K/Akt/GSK3ß signaling pathways.

Negative-pressure therapy versus conventional therapy on split-thickness skin graft: A systematic review and meta-analysis.

OBJECTIVE: To compare the clinical outcomes of negative-pressure wound therapy (NPWT) versus conventional therapy on split-thickness skin after grafting surgery. DESIGN: Meta-analysis. BACKGROUND: Split-thickness skin grafts are widely used in reconstruction of large skin defects. Conventional therapy causes pain during dressing changing. NPWT is an alternative method to cover the wound bed. METHODS: The Pubmed, Embase, and Cochrane databases were searched for randomized controlled trials (RCTs) or cohort studies for articles published between 1993 and April 2017 comparing NPWT to conventional wound therapy for split-thickness skin grafts. The rate of graft take was the primary outcome of this meta-analysis. Wound infection and reoperation rate of the wound were secondary outcomes. Data analysis was conducted using the Review Manager 5.3 software. RESULTS: Five cohort studies and seven RCTs including 653 patients were eligible for inclusion. Patients treated with NPWT had a significantly higher rate of graft take compared to those treated with conventional therapy [MD = 7.02, (95% CI 3.74, 10.31)] (P = .00). NPWT was associated with a reduction in reoperation [RR = 0.28, (95% CI 0.14, 0.55)] (P = .00). The reduction in wound infection was not significant [RR = 0.63, (95% CI 0.31, 1.27)] (P = .20). CONCLUSION: Compared with conventional therapy, NPWT significantly increases the rate of graft take and reduces the rate of reoperation when applied to cover the wound bed with split-thickness skin graft. No significant impact on wound infection was found in this study.

Percutaneous sacroiliac screw versus anterior plating for sacroiliac joint disruption: A retrospective cohort study.

BACKGROUND: Sacroiliac joint disruption (SJD) is a common cause of pelvic ring instability. Clinically, percutaneous unilateral S1 sacroiliac screw and anterior plating are always applied to manage SJD. The objective of this study is to elaborate their respective therapeutic traits. MATERIALS AND METHODS: Patients with SJD fixed with unilateral S1 sacroiliac screw or anterior plating from June 2011 to June 2015 were recruited into this study and were divided into two groups: group A (unilateral sacroiliac screw) and group B (anterior plating). Surgical time, blood loss, frequency of intraoperative fluoroscopy and complications were reviewed. Postoperative radiograph and CT were conducted to assess the reduction quality. Fracture healing was evaluated by radiograph performed at each follow-up. Majeed score was recorded at the final follow-up to assess the functional outcome. RESULTS: Thirty-eight patients were included in group A and thirty-two patients in group B in this study. There was no significant difference in the demographic data of the two groups. A significant difference existed in the results for average operation time (P = .022) and blood loss (P = .000) between group A and group B. The mean frequency of intraoperative fluoroscopy was 15.82 in group A and 3.94 in group B (P = .000). All the fractures healed in this study. The rates of satisfactory reduction quality and functional outcome showed no significant difference between the two groups (P > .05). The complication rate was 15.79% (6/38) in group A and 9.38% (3/32) in group B (P = .660). CONCLUSION: Compared with anterior plating, percutaneous unilateral S1 sacroiliac screw usage is less invasive; however, more intraoperative X-ray exposure and permanent neurologic damage may accompany this procedure.

Liraglutide, a glucagon-like peptide-1 receptor agonist, facilitates osteogenic proliferation and differentiation in MC3T3-E1 cells through phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT), extracellular signal-related kinase (ERK)1/2, and cAMP/protein kinase A (PKA) signaling pathways involving ß-catenin.

Previous studies have proven that glucagon-like peptide-1 (GLP-1) and its receptor agonist exert favorable anabolic effects on skeletal metabolism. However, whether GLP-1 could directly impact osteoblast-mediated bone formation is still controversial, and the underlying molecular mechanism remains to be elucidated. Thus in this paper, we investigated the effects of liraglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, on murine MC3T3-E1 preosteoblasts proliferation and differentiation and explored the potential cellular basis. Our study confirmed the presence of GLP-1R in MC3T3-E1, and demonstrated that liraglutide promotes osteoblasts proliferation at an intermediate concentration (100nM) and time (48h), upregulated the expression of osteoblastogenic biomarkers at various stages, and stimulated osteoblastic mineralization. Liraglutide also elevated the intracellular cAMP level and phosphorylation of AKT, ERK and ß-catenin simultaneously with increased nuclear ß-catenin content and transcriptional activity. Pretreatment of cells with the inhibitors LY294002, PD98059, H89 and GLP-1R and ß-catenin siRNA partially blocked the liraglutide-induced signaling activation and attenuated the facilitating effect of liraglutide on MC3T3-E1 cells. Collectively, liraglutide was capable of acting upon osteoblasts directly through GLP-1R by activating PI3K/AKT, ERK1/2, cAMP/PKA/ß-cat-Ser675 signaling to promote bone formation via GLP-1R. Thus, GLP-1 analogues may be potential therapeutic strategy for the treatment of osteoporosis in diabetics.