Mefenamic acid exhibits antitumor activity against osteosarcoma by impeding cell growth and prompting apoptosis in human osteosarcoma cells and xenograft mice model.

The study investigates the anticancer activity of mefenamic acid against osteosarcoma, shedding light on its underlying mechanisms and therapeutic potential. Mefenamic acid exhibited robust inhibitory effects on the proliferation of MG-63, HOS, and H2OS osteosarcoma cells in a dose-dependent manner. Moreover, mefenamic acid induced cellular toxicity in MG63 cells, as evidenced by LDH leakage, reflecting its cytotoxic impact. Furthermore, mefenamic acid effectively suppressed the migration and invasion of MG-63 cells. Mechanistically, mefenamic acid induced apoptosis in MG-63 cells through mitochondrial depolarization, activation of caspase-dependent pathways, and modulation of the Bcl-2/Bax axis. Additionally, mefenamic acid promoted autophagy and inhibited the PI3K/Akt/mTOR pathway, further contributing to its antitumor effects. The molecular docking studies provide compelling evidence that mefenamic acid interacts specifically and strongly with key proteins in the PI3K/AKT/mTOR pathway, suggesting a novel mechanism by which mefenamic acid could exert anti-osteosarcoma effects. In vivo studies using a xenograft mouse model demonstrated significant inhibition of MG-63 tumor growth without adverse effects, supporting the translational potential of mefenamic acid as a safe and effective therapeutic agent against osteosarcoma. Immunohistochemistry staining corroborated the in vivo findings, highlighting mefenamic acid's ability to suppress tumor proliferation and inhibit the PI3K/AKT/mTOR pathway within the tumor microenvironment. Collectively, these results underscore the promising therapeutic implications of mefenamic acid in combating osteosarcoma, warranting further investigation for clinical translation and development.

[Single Kocher-Langenbeck approach combined with anterograde channel screw technique in treatment of acetabular transverse and posterior wall fractures].

Objective: To assess the effectiveness of the single Kocher-Langenbeck approach combined with anterograde channel screw technique for the treatment of acetabular transverse and posterior wall fractures. Methods: Between March 2020 and October 2022, 17 cases of acetabular transverse and posterior wall fractures were treated with the single Kocher-Langenbeck approach combined with anterograde channel screw technique. There were 11 males and 6 females, with an average age of 53.6 years (range, 42-64 years). Causes of injury included traffic accident in 12 cases, and falling from height in 5 cases. The time from injury to operation ranged from 4 to 16 days with an average of 8.8 days. The operation time, intraoperative blood loss, and fluoroscopy frequency were recorded; X-ray films were reviewed regularly after operation to observe the fracture healing, and postoperative complications were recorded. At last follow-up, Matta score was used to evaluate the reduction of fracture, Harris score and modified Merle D'Aubigné-Postel scores system were used to evaluate the hip joint function. Results: The operation time was 150-230 minutes (mean, 185.9 minutes), the intraoperative blood loss was 385-520 mL (mean, 446.2 mL), and the fluoroscopy frequency was 18-34 times (mean, 27.5 times). Postoperative fat liquefaction occurred in 1 case and the other incisions healed by first intention; 3 cases had limb numbness after operation, and the symptoms disappeared after active symptomatic treatment; no urogenital system and intestinal injury occurred. All patients were followed up 12-28 months (mean, 19.9 months). Bone union was achieved in all cases with an average healing time of 10.8 weeks (range, 8-14 weeks). There was no complication such as loosening and breakage of internal fixators. At last follow-up, according to Matta score, 12 cases achieved anatomic reduction, 3 satisfactory reduction, and 2 fair reduction, the satisfactory rate was 88.2%; according to Harris hip function score, 12 cases were excellent, 3 good, and 2 fair, the excellent and good rate was 88.2%; according to the modified Merle D'Aubign Aubigné-Postel scoring system, the results were excellent in 11 cases, good in 3 cases, and fair in 3 cases, with an excellent and good rate of 82.4%. Conclusion: The single Kocher-Langenbeck approach combined with anterograde channel screw technique is a minimally invasive method for the treatment of acetabular transverse and posterior wall fractures with less complications, simple operation, and satisfactory effectiveness.

[Research progress on evaluation methods for head-neck nail position in femoral intertrochanteric fractures].

Objective: To summarize the research progress on the evaluation methods of head-neck nail positions in femoral intertrochanteric fractures. Methods: The literature about the evaluation methods of head-neck nail positions for femoral intertrochanteric fractures in recent years was extensively reviewed, and research progress in the aspects of evaluation methods, clinical applications, and limitations were summarized. Results: The position of head-neck nails in femoral intertrochanteric fractures is closely related to postoperative complications of head-neck nail cutting. Currently, the tip-apex distance (TAD) and femoral head zoning are widely used to evaluate the position of head-neck nails. The main opinion in the literature is that the use of TAD and femoral head zoning can effectively reduce the incidence of head-neck nails cutting. Parker's ratio, as one of the evaluation methods, has been controversial in subsequent studies and has not been widely used in clinical practice. The TAD as referenced to the calcar (CalTAD), which was modified based on TAD, has been gradually accepted by the clinic, but whether it is better than the TAD has not yet been conclusively determined. In recent years, new evaluation methods have been proposed to supplement the previous evaluation methods, such as the tip-neck distance ratio (TNDR) and the standardized TAD (STAD) to avoid the limitations of the TAD and the CalTAD by the volume of the femoral head, and the axis-blade angle (ABA) to supplement the direction of the head-neck nails channel, but at present the clinical application is relatively underutilized, and the validity of the method needs to be further verified. Conclusion: Currently, there are many methods for evaluating the position of head-neck nails in femoral intertrochanteric fractures, TAD<25 mm combined with head-neck nails placed in the middle-middle quadrant or lower-middle quadrant of the femoral head division is currently a highly recognized assessment in the literature, but the optimal assessment is still controversial, and further research needs to be studied.

A retrospective analysis of minimally invasive internal fixation versus nonoperative conservative management of pelvic ring fragility fractures and the elderly.

OBJECTIVE: We aimed to investigate the adoption of treatment patterns for hip fractures combined with minimally invasive surgical treatment of fragility fractures of the pelvis in older individuals and reviewed and analysed the treatment efficacy and feasibility. METHODS AND DATA: From September 2017 to February 2021, 135 older individuals with fragility fractures of the pelvis were admitted to our hospital. We retrospectively analysed patients who received surgical or conservative treatments. The general preoperative data, including sex, age, disease duration, cause of injury, AO/OTA type, BMI, bone mineral density, time from injury to admission, time from injury to surgery, ASA classification, number of underlying diseases, mean bed rest, clinical fracture healing, VAS score and Majeed functional score, were recorded. RESULTS: The mean follow-up time for all 135 patients was 10.5 ± 3.6 months. Among 135 patients, 95 survived, and 11 and 29 patients passed after the surgical (mortality rate = 17.74%) and conservative (mortality rate = 39.73%) treatments, respectively. The average follow-up time for the 95 surviving patients was 14.5 ± 1.8 months. The Majeed and VAS scores for the operation group were significantly better than those of the conservative group. The bed rest and fracture healing times were also shorter in the surgical treatment group than in the conservative group. CONCLUSION: The use of a minimally invasive surgical treatment combined with the geriatric hip fracture treatment model to treat fragility fractures of the pelvis improved the quality of life in older patients.

Acellular nerve grafts with bone marrow mesenchymal stem cells/Schwann cells for sciatic nerve regeneration in rats: a meta-analysis.

INTRODUCTION: The aim of this meta-analysis was to evaluate the effects of acellular nerve grafts (ANGs) with bone marrow mesenchymal stem cells (BMSCs) or Schwann cells (SCs) on the treatment of sciatic nerve defect in rats. EVIDENCE ACQUISITION: Electronic databases were accessed to identify eligible targets. ANGs data were extracted for meta-analysis using Review Manager 5.3. EVIDENCE SYNTHESIS: The rats subjected to ANGs+BMSCs or ANGs+SCs are characterized by different sciatic nerve function index, nerve conduction, latency, amplitude, myelin sheath thickness, myelinated nerve fibers and gastrocnemius wet weight. accompanied with evidently superior recovery of limb function. These differences are of statistical significance (P<0.05) when compared to that of control group with ANGs only. CONCLUSIONS: ANGs with BMSCs or SCs can promote nerve regeneration and functional recovery in peripheral nerve defects.

Secondary below-knee amputation following open reduction and internal fixation of a closed pilon fracture: A case report and algorithm for management.

RATIONALE: Despite significant advances in surgical techniques and implants, the clinical outcome of high-energy pilon fractures remains unsatisfactory, which continues to represent numerous challenges for orthopedic trauma surgeons. PATIENT CONCERNS: A 62-year-old man injured his right ankle after falling from a 3 m high place. There were no open wounds or other complications. DIAGNOSES: According to the X-ray and CT scans, the patient was diagnosed with pilon fracture (type AO-43-C2) and lateral malleolus fracture of the right limb. INTERVENTIONS: The patient was initially treated with calcaneal traction upon admission to a primary hospital. Five days after the injury, the patient underwent open reduction and internal fixation (ORIF) of the fracture and vacuum sealing drainage (VSD) for wound closure. OUTCOMES: The patient presented to our hospital on the 9th day after the first ORIF operation because of critical ischemia of the affected foot and distal lower leg. Blood circulation did not improve after a series of salvage treatments, and below-knee amputation was ultimately performed. LESSONS: This is a rare case of complete ischemic necrosis following ORIF surgery of a closed pilon fracture due to iatrogenic damage. Standardized treatment that strictly follows the guidelines, instructions, or expert consensus should be promoted in this kind of complicated pilon fracture.

Codelivery of survivin inhibitor and chemotherapeutics by tumor-derived microparticles to reverse multidrug resistance in osteosarcoma.

Reportedly, the elevated expression of survivin has been observed in several tumor types, strictly involved in tumor development. In the present study, we detected elevated survivin expression in tumor tissues derived from patients with chemoresistant osteosarcoma when compared with those from chemosensitive patients. Importantly, knockdown of survivin in osteosarcoma cells significantly suppressed cell proliferation and chemoresistance both in vitro and in vivo. Simultaneously, chemotherapy mediates the upregulation of survivin in osteosarcoma cells through a survivin-based selective killing effect, resulting in the development of multidrug resistance. The utilization of tumor-derived microparticles to coencapsulate the survivin inhibitor YM155 and chemotherapeutic agents could effectively reverse multidrug resistance, leading to improved anticancer effects, as well as reduced systemic toxicity. In summary, the expression of survivin contributes to resistance toward osteosarcoma drugs, whereas employing survivin inhibiting combination therapy, based on a microparticle codelivery system, could efficiently reverse resistance and avoid potential systemic toxicity.

Extracellular Collagen Mediates Osteosarcoma Progression Through an Integrin α2ß1/JAK/STAT3 Signaling Pathway.

BACKGROUND: Osteosarcoma development is a complex set which is determined by various factors. Many patients suffered from sustained osteosarcoma growth and revealed poor response to clinical interventions. However, the underlying mechanisms of osteosarcoma development still remain unclear. METHODS: In our study, we isolated osteosarcoma tissues from clinical patients, which were divided into high degree group (stage G1~G2) and low degree group (stage G0). The expression of type I collagen, integrin and STAT3 in tumor tissues were analyzed by immunohistochemistry or immunofluorescence. The collagen-induced cells proliferation was detected by CCK8 and colony formation analysis. The activation of JAK/STAT3 signal was examined by Western blotting and immunofluorescence. The anticancer effects of integrin α2ß1 peptide were analyzed by Sao-2-bearing mice model. RESULTS: Our results implicated that type I collagen could facilitate malignant osteosarcoma development in patients. In vitro, 2D collagen culture also efficiently mediated the stemness up-regulation of osteosarcoma cells, resulting in the strengthened capability of cells proliferation and tumorigenesis. In mechanism, we found that type I collagen could facilitate the activation of JAK/STAT3 signals through integrin α2ß1, which elicited tumor-sustained growth and cancer relapse. In tumor-bearing mice model, integrin α2ß1 signals inhibitor significantly suppressed the osteosarcoma cells proliferation and their tumorigenic ability, which improved the outcome of chemotherapy/radiotherapy. CONCLUSION: Our study demonstrated that type I collagen could mediate osteosarcoma development through an integrin α2ß1/JAK/STAT3 signaling pathway. Blockade of integrin α2ß1 by α2ß1 inhibitor efficiently improved outcome of chemotherapy/radiotherapy, which provided new insights for eradicating tumors in clinic.

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

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

Ginsenoside Rb1 prevents steroid­induced avascular necrosis of the femoral head through the bone morphogenetic protein­2 and vascular endothelial growth factor pathway.

At present, the molecular mechanism underlying the protective effect of Ginsenoside Rb1 remains unclear. The present study was designed to investigate whether Ginsenoside Rb1 weakened the steroid­induced avascular necrosis of the femoral head (SANFH) and to explore the possible mechanisms of the above effects. As a result, it was revealed that Ginsenoside Rb1 was protective against steroid­induced avascular necrosis and inhibited serum osteocalcin in a rat model of SANFH. Ginsenoside Rb1 reduced inflammation, oxidative stress and bone cell apoptosis in a rat model of SANFH. Furthermore, Ginsenoside Rb1 attenuated trabecula parameters, total cholesterol and low density lipoprotein/high density lipoprotein in SANFH rat. Additionally, Ginsenoside Rb1 significantly reversed alkaline phosphatase and osteocalcin activities, vascular endothelial growth factor (VEGF) receptor, VEGF, Runt related transcription factor 2 (Runx2) and bone morphogenetic protein (BMP)­2 protein expression in SANFH rat. Collectively, the present study demonstrated that Ginsenoside Rb1 attenuated SANFH through the VEGF/RUNX2/BMP­2 signaling pathway.

[SIMULTANEOUS REPAIR OF TIBIA BONE DEFECT AND REFRACTORY SOFT TISSUE DEFECT BY BONE TRANSPORT TECHNIQUE].

OBJECTIVE: To explore the feasibility and effectiveness of bone transport technique for simultaneous repair of tibia defect and refractory soft tissue defect. METHODS: Thirty-five patients with tibia bone defect combined with refractory soft tissue defect were treated between January 2010 and December 2014, and the clinical data were retrospectively analyzed. There were 21 males and 14 females with an average age of 29 years (range, 18-47 years). All patients had Gustilo type Ⅲ open tibial fractures, which were caused by traffic accident. Fracture located at the upper 1/3 of the tibia in 1 case, at the middle 1/3 of the tibia in 19 cases, and at the lower 1/3 of the tibia in 15 cases. All patients underwent external fixation after 4-10 hours of trauma, and tibial skin necrosis, infection, and purulent exudation were observed after 5-10 days of operation. The time from injury to admission was 21 days to 5 months (mean, 2 months). After debridement, the average length of tibia defect was 8 cm (range, 6-11 cm); the area of soft tissue defect was 6 cm×5 cm to 10 cm×8 cm. Orthofix external fixation was applied to tract the bone and soft. RESULTS: All 35 patients were followed up 12-22 months (mean, 16 months). The average time of bony healing was 15 months (range, 9-20 months), and no obvious force line offset was found. Osteotomy segment was extended from 6 to 11 cm (mean, 8 cm); after treatment, the external fixation support was retained for 2 to 10 months (mean, 5 months). No blood vessel and nerve injuries were found during treatment, and no osteomyelitis and refracture happened after operation. The skin and soft tissue defects healed, and the healing time was 1 to 3 months (mean, 1.3 months). Different degrees of infection occurred in 5 cases, and was cured after dressing change. According to Johner-Wruhs' evaluation criteria after external fixator was removed, the results were excellent in 26 cases, good in 5 cases, and moderate in 4 cases, with an excellent and good rate of 88.6%. CONCLUSIONS: Bone transport technique can simultaneously repair tibia bone defect and soft tissue defect by continuous bone and soft tissue traction.

[Therapy of thoracolumbar vertebra tumor by total spondylectomy and spine reconstruction through posterior approach].

OBJECTIVE: To explore the surgical procedure and effectiveness of total spondylectomy and spine reconstruction through posterior approach to treat thoracolumbar vertebra tumor. METHODS: Between June 2004 and July 2008, 14 cases of thoracolumbar vertebra tumor underwent one-stage total spondylectomy through posterior approach and spine reconstruction with posterior pedicle screw system and bone graft. There were 11 males and 3 females with a mean age of 47.2 years (range, 36-60 years). The disease duration was 3-15 months. Affected segments included T3 in 1 case, T4 in 3 cases, T8 in 3 cases, T9 in 2 cases, T10 in 3 cases, T12 in 1 case, and L1 in 1 case. The postoperative pathological results were 3 cases of bony giant cell tumor, 1 case of osteoblastoma, 2 cases of osteosarcoma, and 8 cases of metastatic tumor. According to Tomita et al. grading system, there were 1 case of type II, 5 cases of type III, 3 cases of type IV, and 5 cases of type V. According to Frankel classification of preoperative spinal cord function, 3 cases were rated as grade B, 4 as grade C, 5 as grade D, and 2 as grade E. RESULTS: Wound healing by first intention was obtained in all cases, and no blood vessel and nerve injury occurred. Fourteen patients were followed up 11-64 months (mean, 32.5 months). The local pain was relieved significantly. At 6-8 months after operation, the X-ray films and CT showed that bone graft fusion at Bridwell I grade was achieved. At 10 months, the postoperative spinal cord function was improved from grade B to grade D in 2 cases, from grade C to grade D in 1 case, and the other 9 cases reached grade E. The patients had normal walking function. Two patients died of liver metastasis and brain metastasis at 11 and 15 months postoperatively, respectively; 1 patient with osteoscarcoma died of lung metastasis at 16 months; and 1 case of osteoscarcoma developed local recurrence at 8 months postoperatively. Internal fixation was reliable without loosening and breakage and the spine was stable. CONCLUSION: Total spondylectomy and spine reconstruction through posterior approach is an effective method with advantages of relative minimal injury, radical tumor excision, low local recurrence, and adequate spinal cord decompression.