Causal effects of osteoporosis on structural changes in specific brain regions: a Mendelian randomization study.

Observational studies have reported that osteoporosis is associated with cortical changes in the brain. However, the inherent limitations of observational studies pose challenges in eliminating confounding factors and establishing causal relationships. And previous observational studies have not reported changes in specific brain regions. By employing Mendelian randomization, we have been able to infer a causal relationship between osteoporosis and a reduction in the surficial area (SA) of the brain cortical. This effect is partially mediated by vascular calcification. We found that osteoporosis significantly decreased the SA of global brain cortical (ß = -1587.62 mm2, 95%CI: -2645.94 mm2 to -529.32 mm2, P = 0.003) as well as the paracentral gyrus without global weighted (ß = - 19.42 mm2, 95%CI: -28.90 mm2 to -9.95 mm2, P = 5.85 × 10-5). Furthermore, we estimated that 42.25% and 47.21% of the aforementioned effects are mediated through vascular calcification, respectively. Osteoporosis leads to a reduction in the SA of the brain cortical, suggesting the presence of the bone-brain axis. Vascular calcification plays a role in mediating this process to a certain extent. These findings establish a theoretical foundation for further investigations into the intricate interplay between bone, blood vessels, and the brain.

Fracture risks in patients with atrial fibrillation treated with different oral anticoagulants: a meta-analysis and systematic review.

AIMS: evidence on the difference in fracture risks for patients with atrial fibrillation (AF) receiving direct oral anticoagulants (DOACs) versus warfarin remains controversial. We aim to compare the fracture risks between the DOAC and warfarin prescriptions among the AF patients. METHODS AND RESULTS: we systematically searched PubMed, EMBASE, the Cochrane Library and Web of Science up to 19 April 2021 for relevant studies. And the observational studies regarding the relationship between the DAOC versus warfarin prescriptions and fracture risks among the patients with AF were included in this meta-analysis. Two investigators independently screened the articles and extracted the relevant data. A random- or fixed-effect model was applied to calculate the pooled hazard ratio/relative ratios with 95% confidence intervals of fracture risks associated with the DOAC and warfarin prescriptions. Six studies comprising 351,208 patients and 9,424 fractures were included in this meta-analysis. Overall, the AF patients treated with DOACs tend to present a lower risk of any fracture compared with those treated with warfarin (relative ratio: 0.82, 95% confidence interval (CI): 0.74-0.91). Sub-analyses for each individual DOAC indicate that apixaban and rivaroxan are associated with lower risk of any fracture compared with warfarin (HR: 0.75, 95% CI: 0.60-0.92, and HR: 0.79, 95% CI: 0.71-0.88, respectively). CONCLUSION: this meta-analysis suggests that DOAC users have a lower risk of fractures than the warfarin users. The results of this study may provide optimal anticoagulation opportunities for AF patients with high fracture risk factors.

Changes of Migration, Immunoregulation and Osteogenic Differentiation of Mesenchymal Stem Cells in Different Stages of Inflammation.

Bone infection has always been the focus of orthopedic research. Mesenchymal stem cells (MSCs) are the natural progenitors of osteoblasts, and the process of osteogenesis is triggered in response to different signals from the extracellular matrix. MSCs exert important functions including secretion and immune regulation and also play a key role in bone regeneration. The biological behavior of MSCs in acute and chronic inflammation, especially the transformation between acute inflammation and chronic inflammation, has aroused great interest among researchers. This paper reviews the recent literature and summarizes the behavior and biological characteristics of MSCs in acute and chronic inflammation to stimulate further research on MSCs and treatment of bone diseases.

Brachial muscle injury resulting in acute compartment syndrome of the upper arm: a case report and literature review.

BACKGROUND: Acute compartment syndrome (ACS) is a potentially devastating condition. ACS is rare in the upper arm. CASE PRESENTATION: We report a case of acute compartment syndrome of the anterior compartment of the upper arm due to brachial muscle injury. The patient experienced abnormal progressive swelling and pain in his right upper arm, and passive pulling pain of the right wrist and right hand. It was highly suspected to be right upper arm compartment syndrome, and was confirmed by surgery. The patient transferred to the emergency operating room for fasciotomy that was performed under general anesthesia using the anterolateral approach. The brachial muscle was found to be heavily swollen and had the greatest tension. The brachial muscle fibers were split lengthwise, and a large amount of hematoma was cleared. The brachial muscles were injured and partly ruptured. After full decompression, a negative pressure drainage device was used to cover the wound in the first stage. Ten days after injury, the swelling of the affected limb subsided and the wound was sutured. The patient's limbs completely recovered to normal. The shoulder and elbow joints could move freely and the patient resumed normal farming work ability. CONCLUSION: Clinicians should fully recognize the fact that acute compartment syndrome can occur in the upper arm, rather than only the forearm and leg, and therefore avoid serious consequences caused by missed diagnosis and misdiagnosis.

Comparison of single versus double TightRope system in the treatment of acute acromioclavicular joint dislocation.

BACKGROUND: Reconstruction of the coracoclavicular (CC) ligament using a single TightRope (ST) system has some complications. We attempted to use a double TightRope (DT) system to reduce complications and obtain the ideal therapeutic effect. PURPOSE: This investigation aimed to compare the ST and DT systems in terms of efficacy and safety in treating acromioclavicular (AC) joint dislocation. METHODS: Sixty-six cases of acute AC joint dislocation between January 2013 and January 2018 were retrospectively reviewed. All patients were divided into 2 groups based on treatment with the ST or DT system. Patients were evaluated radiologically and clinically using the Disability of Arm, Shoulder, and Hand, Constant, and visual analog scale scores as clinical outcome measures at 1 day, 3 weeks, 6 weeks, 3 months, 6 months, 1 year, and 2 years after surgery. The CC distance and displacement ratio were assessed radiologically. RESULTS: The mean follow-up period was 49 months. Satisfactory clinical outcomes were obtained after CC fixation in both groups. No intergroup difference was found regarding the visual analog scale (P = .80), Disability of Arm, Shoulder, and Hand (P = .42), or Constant score (P = .28) at 2 years. However, there was a significant difference in the displacement ratio at 6 weeks (P < .0001), 3 months (P < .0001), 6 months (P < .0001), 1 year (P < .0001), and 2 years (P < .0001) postoperatively between the 2 groups. There were 3 complications in the ST group, including 1 case of secondary coracoid fracture, 1 case of AC joint arthrosis combined with ossification of the CC ligaments, and 1 case of clavicular erosion. All complications occurred in the ST group. CONCLUSIONS: Both surgical methods are effective in treating AC joint dislocation, but the DT system is more reliable for reduction maintenance.

The Process of Osteoblastic Infection by Staphylococcus Aureus.

Bone infection is difficult to cure, and relapse frequently occurs, which is a major treatment problem. One of the main reasons for the refractory and recurrent nature of bone infection is that bacteria, such as Staphylococcus aureus (S. aureus), can be internalized into osteoblasts after infecting bone tissue, thereby avoiding attack by the immune system and antibiotics. Understanding how bacteria (such as S. aureus) are internalized into osteoblasts is key to effective treatment. S. aureus is the most common pathogenic bacterium that causes bone infection. This paper reviews the literature, analyzes the specific process of osteoblastic S. aureus infection, and summarizes specific treatment strategies to improve bone infection treatment.

Distal locked versus unlocked intramedullary nailing for stable intertrochanteric fractures, a systematic review and meta-analysis.

BACKGROUND: Intramedullary nails have become the main treatment for intertrochanteric fractures. However, a distal locking procedure during nailing gradually raised controversy. In this study, a systematic review and meta-analysis of clinical trials was performed to summarize existing evidence, aiming to determine the safety and efficacy of distal locking or unlocking in the nailing of stable intertrochanteric fractures. METHODS: Appropriate articles were identified using the most common public databases, such as PubMed, Embase, the Cochrane Library, and Google Scholar from the inception of each database to April 2019, without restriction of language, publication date, and considering ongoing trials. Eligible studies were represented by randomized controlled trials or retrospective cohort studies, comparing distal locking and unlocking for the treatment of acute stable intertrochanteric fractures in adult patients. Information regarding methodological quality, patient demographics, and clinical outcomes were extracted independently by two reviewers. Subsequently, patients were divided into a locking and unlocking group. RESULTS: This study included 9 articles, comprising a total of 1978 patients with a similar baseline. The results showed that the unlocking group had a shorter operation time, less intraoperative bleeding, lower transfusion rate, and less thigh pain after the treatment of femoral intertrochanteric fracture when compared with the distal locking group. No significant differences were observed in safety-related outcomes, including mortality, infection rate, cutting out, loss of reduction, backing out of lag screws, cephalic screw breakage, nail breakage, and peri-implant fractures between the two groups. In addition, efficacy-related outcomes including nonunion, delayed healing rates, and the Harris functional score were not significantly different between the two groups. CONCLUSIONS: Our pooled analysis demonstrated that distal unlocking of stable intertrochanteric fractures can shorten the operation time, reduce intraoperative bleeding, and reduce the blood transfusion rate. The use of locked or unlocked intramedullary nailing does not affect long-term outcomes regarding complications and function.

Popliteal artery transection associated with a minimally displaced tibial plateau fracture: a case report and review of the literature.

BACKGROUND: Poplital artery transection injury is potentially catastrophic, or even life-threatening. Severe traumas, including open fracture, gunshot, stabs, and knee dislocation and complex fracture of proximal tibia or distal femur, are the common causes of high rate of amputation due to popliteal artery trauma. No report mentions vascular injury associated with minimally displaced tibial plateau fracture in adult. CASE PRESENTATION: A 30-year-old male presented with popliteal artery transection injury associated with minimally displaced tibial plateau fracture. He presented to emergency department, 6 h after fall from ground into a 1-m height hole. Physical examination suggested acute ischemia, with signs of paleness, coldness, anesthesia, hemorrhagic bullae below the right knee level. There was severe swelling and ecchymosis in popliteal fossa and around the leg with significant calf tenderness and pedal edema. Tibialis posterior, dorsalis pedis, and popliteal arterial pulses were not palpable. Radiograph suggested minimally displaced tibial plateau fracture with no evidence of knee dislocation. The patient was taken up for emergency surgery after consultation with vascular surgeon. During the closed reduction external fixation and compartment decompression, popliteal artery trunk was found transected and end-to-end repair was performed. During the post-operational period, no complication was developed and the patient was followed-up for 1 year. At the one-year follow-up, he acquired good stability of his right knee with full range of motion. CONCLUSION: Significant swelling and ecchymosis should alert the surgeons to the possibility of vascular injury in knee joint injury, even if there is no fracture or dislocation, or fracture is minimally displaced.

Study and Therapeutic Progress on Intracranial Serpentine Aneurysms.

An intracranial serpentine aneurysm (SA) is a clinically rare entity, and very few multi-case studies on SA have been published. The present study reviewed the relevant literature available on PubMed. The studied information included the formation mechanism and natural history of SA as well as its clinical manifestation, imaging characteristics, and current treatments. After reviewing the literature, we conclude that intracranial SA can be managed surgically and by endovascular embolization, but the degree of blood flow in normal brain tissue distal to the SA must be evaluated. A balloon occlusion test (BOT) or cross compression test is recommended for this evaluation. If the collateral circulation is sufficiently compensatory, direct excision or embolization can be performed. However, if the compensatory collateral circulation is poor, a bypass surgery is necessary. Satisfactory results can be achieved in the majority of SA patients after treatment. However, the size of the aneurysm may increase in some patients after endovascular treatment. Special attention should be paid to cases exhibiting a significant mass effect to avoid subsequent SA excision due to an intolerable mass effect. Satisfactory results can be achieved with careful treatment of SA.

A new device for efficient preparation of standard antibiotic bead chains and customized antibiotic delivery.

Antibiotic-loaded polymethylmethacrylate (PMMA) beads are widely used in orthopedic practice for the prevention of infections after open fractures and in the management of osteomyelitis. The use of commercial beads is limited by insufficient flexibility, lack of provision for selection of specific antibiotic, and short drug-release time. Further, the manual procedure for the preparation of PMMA beads is slow, and the products are not uniform in size. Uniformity of the bead size is crucial because the placement of oversized beads place at sites with limited space (e.g., narrow medullary canal) is difficult, and their retrieval from such sites is painful to the patient. To overcome the limitations of commercial beads and manually prepared beads, we developed a simple device for the efficient preparation of antibiotic-loaded PMMA beads of uniform sizes. We describe the device, bead preparation, and the characteristics of the beads prepared using our device, and the preliminary clinical results. The beads obtained using this device were relatively small, had excellent flexibility, and were suitable for implantation in small spaces. The device permits the selection of the antibiotic to be loaded on to the beads. The results of preliminary studies of the beads prepared using our device have been positive, highlighting the need for more large-scale and longitudinal investigations.

Incidence and risk factors for venous thromboembolism following surgical treatment of fractures below the hip: a meta-analysis.

Venous thromboembolism (VTE) is a common complication after surgical treatment of fractures, which is associated with significant morbidity and mortality. Identifying the risk factors for VTE is important for preventive strategies to reduce the incidence of VTE. Therefore, we conducted a meta-analysis to evaluate the incidence of VTE and the risk factors influencing the development of VTE in patients who underwent surgery for fractures below the hip. PubMed, Embase, Web of Science, SinoMed (Chinese BioMedical Literature Service System, China) and CNKI (National Knowledge Infrastructure, China) databases were systematically searched to identify cohort or case-control studies that investigated the incidence and risk factors for VTE following surgical treatment of fractures below the hip. VTE risk ratios (RRs) were pooled by use of a fixed-effect model or a random-effect model, depending on the heterogeneity among the included studies. Heterogeneity between the studies was assessed by I2 statistics. Twenty-three studies with a total of 191 294 patients who met the inclusion criteria were included in this meta-analysis. Our results demonstrated that age (≥60 years) (RR = 1·85, 95% confidence interval (CI): 1·34, 2·55; P = 0·000), previous VTE(RR = 5·25, 95% CI: 2·77, 9·96; P = 0·000), heart failure (RR = 1·74, 95% CI: 1·34, 2·27; P = 0·000), current smoking status (RR = 1·23, 95% CI: 1·07, 1·41; P = 0·004), hypertension (RR = 1·62, 95% CI: 1·27, 2·06; P = 0·000), hyperlipidaemia (RR = 2·16, 95% CI: 1·79, 2·62; P = 0·000), diabetes mellitus (RR = 1·46, 95% CI: 1·27, 1·68; P = 0·000), obesity (RR = 1·58, 95% CI: 1·35,·1·85; P = 0·000), multiple fractures (RR = 2·14, 95% CI: 1·00, 4·60; P = 0·050), varicose veins (RR = 3·07, 95% CI: 1·12, 8·47; P = 0·030), prolonged operation time (weighted mean differences (WMD) = 1·22, 95% CI: 0·63, 1·81; P = 0·000) and prolonged bed rest time (WMD = 3·12, 95% CI: 2·96, 3·29; P = 0·000) were associated with an increased risk of developing VTE. The other variables, including age (<60 years), previous smoking, immobility, pregnancy, cancer, open fractures and combination with trauma were not identified as significant risk factors for VTE. Almost all the risk factors mentioned above are in line with the known risk factors for VTE following surgery for fractures below the hip. Thus, surgeons should pay close attention to patients with these medical conditions in order to reduce the incidence of VTE following surgical treatment of fractures below the hip.

Current Status of the Application of Intracranial Venous Sinus Stenting.

The intracranial venous sinus is an important component of vascular disease. Many diseases involve the venous sinus and are accompanied by venous sinus stenosis (VSS), which leads to increased venous pressure and high intracranial pressure. Recent research has focused on stenting as a treatment for VSS related to these diseases. However, a systematic understanding of venous sinus stenting (VS-Stenting) is lacking. Herein, the literature on idiopathic intracranial hypertension (IIH), venous pulsatile tinnitus, sinus thrombosis, high draining venous pressure in dural arteriovenous fistula (AVF) and arteriovenous malformation (AVM), and tumor-caused VSS was reviewed and analyzed to summarize experiences with VS-Stenting as a treatment. The literature review showed that satisfactory therapeutic effects can be achieved through stent angioplasty. Thus, the present study suggests that selective stent release in the venous sinus can effectively treat these diseases and provide new possibilities for treating intracranial vascular disease.

Shockwaves induce osteogenic differentiation of human mesenchymal stem cells through ATP release and activation of P2X7 receptors.

Shockwave treatment promotes bone healing of nonunion fractures. In this study, we investigated whether this effect could be due to adenosine 5'-triphosphate (ATP) release-induced differentiation of human mesenchymal stem cells (hMSCs) into osteoprogenitor cells. Cultured bone marrow-derived hMSCs were subjected to shockwave treatment and ATP release was assessed. Osteogenic differentiation and mineralization of hMSCs were evaluated by examining alkaline phosphatase activity, osteocalcin production, and calcium nodule formation. Expression of P2X7 receptors and c-fos and c-jun mRNA was determined with real-time reverse transcription polymerase chain reaction and Western blotting. P2X7-siRNA, apyrase, P2 receptor antagonists, and p38 MAPK inhibitors were used to evaluate the roles of ATP release, P2X7 receptors, and p38 MAPK signaling in shockwave-induced osteogenic hMSCs differentiation. Shockwave treatment released significant amounts (≈ 7 µM) of ATP from hMSCs. Shockwaves and exogenous ATP induced c-fos and c-jun mRNA transcription, p38 MAPK activation, and hMSC differentiation. Removal of ATP with apyrase, targeting of P2X7 receptors with P2X7-siRNA or selective antagonists, or blockade of p38 MAPK with SB203580 prevented osteogenic differentiation of hMSCs. Our findings indicate that shockwaves release cellular ATP that activates P2X7 receptors and downstream signaling events that caused osteogenic differentiation of hMSCs. We conclude that shockwave therapy promotes bone healing through P2X7 receptor signaling, which contributes to hMSC differentiation.

A retrospective comparison of the modified tension band technique and the parallel titanium cannulated lag screw technique in transverse patella fracture.

OBJECTIVE: To compare efficacy between the modified tension band technique and the parallel titanium cannulated lag screw technique for the transverse patella fracture. METHODS: Seventy-two patients were retrospectively analyzed aged 22 to 79 years (mean, 55.6 years) with transverse patella fractures, among whom 37 patients underwent the modified tension band and 35 patients received the titanium cannulated lag screw. Patients were followed up for 1-3 years. We analyzed the difference of operation time, complications, fracture reduction, fracture healing time, and the Iowa score for knee function between both groups. RESULTS: In modified tension band group, five patients had skin irritation and seven suffered wire migration, two of whom required a second operation. In comparison, there were no complications in the titanium cannulated lag screw group, which also had a higher fracture reduction rate and less operation time. CONCLUSION: The parallel titanium cannulated lag screw technique has superior results and should be considered as an alternative method to treat transverse patella fracture.

Low-energy shock waves promote the cisplatin chemosensitivity of human osteosarcoma MNNG/HOS cells via the P2X7/Akt/mTOR pathway.

Background: The current dilemma of osteosarcoma treatment is the resistance of chemotherapeutic drugs after long-term usage, which also introduces life-threatening side effects. Methods and results: To minimize chemoresistance in osteosarcoma patients, the authors applied shock waves (SWs) to human osteosarcoma MNNG/HOS cells, then evaluated the cell viability and extracellular ATP levels, and further investigated the effect of SWs on cisplatin (DDP) cytotoxicity in MNNG/HOS cells. The authors' results showed that 400 SW pulses at 0.21 mJ/mm2 exhibited little influence on the MNNG/HOS cell viability. In addition, this SW condition significantly promoted the extracellular ATP release in MNNG/HOS cells. Importantly, low-energy SWs obviously increased Akt and mammalian target of rapamycin (mTOR) phosphorylation and activation in MNNG/HOS cells, which could be partially reversed in the presence of P2X7 siRNA. The authors also found that low-energy SWs strongly increased the DDP sensitivity of MNNG/HOS cells in the absence of P2X7. Conclusions: For the first time, the authors found that SW therapy reduced the DDP resistance of MNNG/HOS osteosarcoma cells when the ATP receptor P2X7 was downregulated. SW therapy may provide a novel treatment strategy for chemoresistant human osteosarcoma.

Shock wave assisted intracellular delivery of antibiotics against bone infection with Staphylococcus aureus via P2X7 receptors.

Background: Treatment of chronic osteomyelitis (bone infection) remains a clinical challenge; in particular, it requires enhanced delivery of antibiotic drugs for the treatment of intracellular Staphylococcus aureus (S. aureus), which prevents infection recurrence and resistance. Previous studies have found that noninvasive shock waves used to treat musculoskeletal diseases can alter cell permeability, however, it is unclear whether shock waves alter cell membrane permeability in chronic osteomyelitis. Furthermore, it remains unknown whether such changes in permeability promote the entry of antibiotics into osteoblasts to exert antibacterial effects. Methods: In our study, trypan blue staining was used to determine the shock wave parameters that had no obvious damage to the osteoblast model; the effect of shocks waves on the cell membrane permeability of osteoblast model was detected by BODIPY®FL vancomycin; high performance liquid chromatography-mass spectrometry (HLPC-MS) was used to detect the effect of shock wave on the entry of antibiotics into the osteoblast model; plate colony counting method was used to detect the clearance effect of shock wave assisted antibiotics on S. aureus in the osteoblast model. To explore the mechanism, the effect of different pulses of shock waves on S. aureus was examined by plate colony counting method, besides, P2X7 receptor in osteoblast was detected by immunofluorescence and the extracellular ATP levels was detected. Furthermore, the effect of P2X7 receptor antagonists KN-62 or A740003 on the intracellular antibacterial activity of shock-assisted antibiotics was observed. Then, we used S. aureus to establish a rat model of chronic tibial osteomyelitis and investigated the efficacy and safety of shock-wave assisted antibiotics in the treatment of chronic osteomyelitis in rats. Results: The viability of the osteoblast models of intracellular S. aureus infection was not significantly affected by the application of up to 400 shock wave pulses at 0.21 mJ/mm2. Surprisingly, the delivery of BODIPY®FL vancomycin to osteoblast model cells was markedly enhanced by this shock wave treatment. Furthermore, the shock wave therapy increased the delivery of hydrophilic antibiotics (vancomycin and cefuroxime sodium), but not lipophilic antibiotics (rifampicin and levofloxacin), which improved the intracellular antibacterial effect. Afterwards, we discovered that shock wave treatment increased the extracellular concentration of ATP (the P2X7 receptor activator)， while KN-62 or A740003, a P2X7 receptor inhibitor, decreased intracellular antibacterial activity. We then found that 0.1 mL of 1 × 1011 CFU/mL ATCC25923 S. aureus was suitable for modeling chronic osteomyelitis in rats. Besides, the shock wave-assisted vancomycin treatment with the strongest antibacterial and osteogenic effects among the tested treatments was confirmed in vivo by imaging examination, microbiological cultures, and histopathology, with favorable safety. Conclusions: Our results suggest that shock waves can promote the entry of antibiotics into osteoblasts for antibacteria by changing the cell membrane permeability in a P2X7 receptor-dependent manner. Besides, considering antibacterial and osteogenic efficiency and a high degree of safety in rat osteomyelitis model, shock wave-assisted vancomycin treatment may thus represent a possible adjuvant therapy for chronic osteomyelitis.

Causal associations of anthropometric measurements with osteoarthritis: A Mendelian randomization study.

OBJECTIVE: We believe that there is a causal relationship between waist circumference and knee osteoarthritis. To confirm the hypothesis, we have conducted this study. METHODS: Genetic variants associated with the five anthropometric variables were obtained from previous large-scale genomewide association studies. Summary-level data on osteoarthritis were obtained from the UK Biobank. The univariable and multivariable MR framework were used to evaluate the associations. The two-sided p value was considered to be statistically significant at 0.01 (where p = 0.05/5) after Bonferroni correction for the five exposure variables. RESULTS: In the univariable MR, there was evidence of a detrimental effect of height, weight, BMI, waist circumference, and hip circumference on osteoarthritis risk in the main IVW analyses (height: OR 1.115, 95% CI 1.054-1.180; weight: OR 1.765, 95% CI 1.650-1.889; BMI: OR 1.952, 95%CI 1.841-2.068; waist circumference: OR 2.140, 95% CI 1.994-2.296; hip circumference: OR 1.719, 95% CI 1.600-1.846). And the analyses on knee osteoarthritis and hip osteoarthritis yielded similar results. However, the multivariable MR showed that only waist circumference was causally associated with osteoarthritis, after adjusting for the confounding exposure effects (waist circumference: OR 1.877, 95% CI 1.286-2.739). Such association was also repeated in the analyses on knee osteoarthritis but not hip osteoarthritis. CONCLUSION: Our study highlighted the causal associations between waist circumference and knee osteoarthritis risk.

Cardiovascular risk factors mediating the protective effect of education on cervical spondylosis risk.

The causal association between education and cervical spondylosis may be mediated partly through risk factors of cardiovascular disease. The identification of the protective effect of education and the evaluation of risk factors will help to optimize disease prevention at both clinical and public health levels. In this study, we applied several different Mendelian randomization (MR) methods to identify which cardiovascular factors underlie the clustering of cervical spondylosis with cardiovascular disease, and the degree to which these mediate an effect of education. Univariable MR analyses provided evidence supporting a protective effect of genetically predicted education on cervical spondylosis risk, and MVMR further identified the direct effect of education level. Our results also provided evidence supporting the detrimental effects of BMI and smoking on cervical spondylosis risk, with evidence that the effect of education is mediated through BMI and smoking. The proportions of the effect of education mediated through BMI and smoking were 12% and 3%, respectively. These findings highlight education, obesity, and smoking as common mechanisms underlying the clustering of cervical spondylosis with risk factors of cardiovascular disease, which might represent clinical and public health targets for reducing multi-morbidity and the burden of these common conditions.

Gamma Nail Combined with One Cannulated Compression Screw Fixation for Treating Pauwels Type III Femoral Neck Fractures in Young and Middle-Aged Adults: Clinical Follow-Up and Biomechanical Studies.

OBJECTIVE: Recently, some clinical studies have reported the use of an intramedullary nailing system for treating unstable femoral neck fractures or femoral neck fractures combined with femoral shaft fractures in young adults, and the results have indicated certain advantages. However, no study has investigated the mechanical properties of this method. We aimed to evaluate the mechanical stability and clinical efficacy of the Gamma nail combined with one cannulated compression screw (CCS) fixation for treating Pauwels type III femoral neck fracture in young and middle-aged adults. METHODS: This study consists of two parts: a clinical retrospective study and randomized controlled biomechanical test. Twelve adult cadaver femora were used to test and compare the biomechanical properties among three fixation methods: three parallel CCS (group A), Gamma nail (group B), and Gamma nail combined with one cannulated compression screw (group C). The single continuous compression test, cyclic load test, and ultimate vertical load test were used to evaluate the biomechanical performance of the three fixation methods. We also conducted a retrospective study of 31 patients with Pauwels type III femoral neck fractures, including 16 patients with fractures fixed with three parallel CCS (CCS group) and 15 patients with fractures fixed with Gamma nail combined with one CCS (Gamma nail + CCS group). The patients were followed up for at least 3 years, and all were evaluated for surgical time (from skin incision to closure), surgical blood loss, hospital stay, and the Harris hip score. RESULTS: In mechanical experiments, we have found that the mechanical advantages of Gamma nail fixation are not as good as those of conventional CCS fixation. However, the mechanical properties of Gamma nail fixation combined with one cannulated screw perpendicular to the fracture line are much better than those of Gamma nail fixation and CCS fixation. No significant difference was found in the incidence of femoral head necrosis and nonunion between the CCS and Gamma nail + CCS groups. Moreover, there was no statistically significant difference in the Harris hip scores between the two groups. One patient in the CCS group showed significant withdrawal of cannulated screws at 5 months after surgery, whereas in the Gamma nail + CCS group, all patients, including those with femoral neck necrosis, showed no loss of stability of the fixation. CONCLUSION: Among the two fixation methods evaluated in this study, Gamma nail combined with one CCS fixation showed better biomechanical properties and may reduce complications associated with unstable fixation devices.

Silicone rubber sealed channel induced self-healing of large bone defects: Where is the limit of self-healing of bone?

Background: Large defects of long tubular bones due to severe trauma, bone tumor resection, or osteomyelitis debridement are challenging in orthopedics. Bone non-union and other complications often lead to serious consequences. At present, autologous bone graft is still the gold standard for the treatment of large bone defects. However, autologous bone graft sources are limited. Silicon rubber (SR) materials are widely used in biomedical fields, due to their safety and biocompatibility, and even shown to induce nerve regeneration. Materials and methods: We extracted rat bone marrow mesenchymal stem cells (BMMSCs) in vitro and verified the biocompatibility of silicone rubber through cell experiments. Then we designed a rabbit radius critical sized bone defect model to verify the effect of silicone rubber sealed channel inducing bone repair in vivo. Results: SR sealed channel could prevent the fibrous tissue from entering the fracture end and forming bone nonunion, thereby inducing self-healing of long tubular bone through endochondral osteogenesis. The hematoma tissue formed in the early stage was rich in osteogenesis and angiogenesis related proteins, and gradually turned into vascularization and endochondral osteogenesis, and finally realized bone regeneration. Conclusions: In summary, our study proved that SR sealed channel could prevent the fibrous tissue from entering the fracture end and induce self-healing of long tubular bone through endochondral osteogenesis. In this process, the sealed environment provided by the SR channel was key, and this might indicate that the limit of self-healing of bone exceeded the previously thought. The translational potential of this article: This study investigated a new concept to induce the self-healing of large bone defects. It could avoid trauma caused by autologous bone extraction and possible rejection reactions caused by bone graft materials. Further research based on this study, including the innovation of induction materials, might invent a new type of bone inducing production, which could bring convenience to patients. We believed that this study had significant meaning for the treatment of large bone defects in clinical practice.