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Lipid nanovehicles are currently the most advanced vehicles used for RNA delivery, as demonstrated by the approval of patisiran for amyloidosis therapy in 2018. To illuminate the unique superiority of lipid nanovehicles in RNA delivery, in this review, we first introduce various RNA therapeutics, describe systemic delivery barriers, and explain the lipid components and methods used for lipid nanovehicle preparation. Then, we emphasize crucial advances in lipid nanovehicle design for overcoming barriers to systemic RNA delivery. Finally, the current status and challenges of lipid nanovehicle-based RNA therapeutics in clinical applications are also discussed. Our objective is to provide a comprehensive overview showing how to utilize lipid nanovehicles to overcome multiple barriers to systemic RNA delivery, inspiring the development of more high-performance RNA lipid nanovesicles in the future.
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Light-based three-dimensional (3D) printing of hydrogels has been widely adopted for accelerating bone regeneration. However, the design principles of traditional hydrogels do not take into consideration the biomimetic regulation of multiple stages throughout the bone healing, and the hydrogels made cannot effectively induce sufficient osteogenesis, which in turn greatly limits their capacity in guiding bone regeneration. The recent progress achieved in DNA hydrogel, which is based on synthetic biology, could facilitate the innovation of the current strategy due to its advantages, such as resistance to enzymatic degradation, programmability, structural controllability, and mechanical properties. However, 3D printing of DNA hydrogel is not well defined and appears to have a few distinct early forms. In this article, a perspective on the early development of 3D printing of DNA hydrogels is presented, and a potential implication of the hydrogel-based bone organoids built-up for bone regeneration is proposed.
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Osteoporotic fractures secondary to osteoporosis increase very rapidly in incidence, and have become a major cause of disability and mortality in the elderly population. Currently, there have no standard guidelines for perioperative management, surgery and postoperative rehabilitation, causing multiple complications and poor therapeutic outcome. The authors previously proposed bone repair strategies including active anti-osteoporosis, adequate bone grafting and bone healing acceleration, namely "three-in-one" bone repair strategy. The care steps in osteoporotic fracture surgery inluded perioperative management, operative precaution, and postoperative prevention of secondary fractures. With this in mind, the authors further discussed the detailed application of "three-in-one" bone repair strategy including perioperative active anti-osteoporosis treatment, early rehabilitation training, standardized internal fixation selection, standard bone grafting methods and prevention of secondary complications, so as to promote the standardized treatment of osteoporotic fractures and improve the prognosis.
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Chronic refractory wound (CRW) is one of the most challengeable issues in clinic due to complex pathogenesis, long course of disease and poor prognosis. Experts need to conduct systematic summary for the diagnosis and treatment of CRW due to complex pathogenesis and poor prognosis, and standard guidelines for the diagnosis and treatment of CRW should be created. The Guideline forthe diagnosis and treatment of chronic refractory wounds in orthopedic trauma patients ( version 2023) was created by the expert group organized by the Chinese Association of Orthopedic Surgeons, Chinese Orthopedic Association, Chinese Society of Traumatology, and Trauma Orthopedics and Multiple Traumatology Group of Emergency Resuscitation Committee of Chinese Medical Doctor Association after the clinical problems were chosen based on demand-driven principles and principles of evidence-based medicine. The guideline systematically elaborated CRW from aspects of the epidemiology, diagnosis, treatment, postoperative management, complication prevention and comorbidity management, and rehabilitation and health education, and 9 recommendations were finally proposed to provide a reliable clinical reference for the diagnosis and treatment of CRW.
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Periarticular fracture of the shoulder is a common type of fractures in the elderly. Postoperative adverse events such as internal fixation failure, humeral head ischemic necrosis and upper limb dysfunction occur frequently, which seriously endangers the exercise and health of the elderly. Compared with the fracture with normal bone mass, the osteoporotic periarticular fracture of the shoulder is complicated with slow healing and poor rehabilitation, so the clinical management becomes more difficult. At present, there is no targeted guideline or consensus for this type of fracture in China. In such context, experts from Youth Osteoporosis Group of Chinese Orthopedic Association, Orthopedic Expert Committee of Geriatrics Branch of Chinese Association of Gerontology and Geriatrics, Osteoporosis Group of Youth Committee of Chinese Association of Orthopedic Surgeons and Osteoporosis Committee of Shanghai Association of Chinese Integrative Medicine developed the Chinese expert consensus on the diagnosis and treatment of osteoporotic periarticular fracture of the shoulder in the elderly ( version 2023). Nine recommendations were put forward from the aspects of diagnosis, treatment strategies and rehabilitation of osteoporotic periarticular fracture of the shoulder, hoping to promote the standardized, systematic and personalized diagnosis and treatment concept and improve functional outcomes and quality of life in elderly patients with osteoporotic periarticular fracture of the shoulder.
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Objective:To compare the clinical results of modified posterolateral approach combined medial approach versus traditional posterolateral approach combined with medial approach in open reduction and internal fixation of trimalleolar ankle fracture.Methods:A retrospective cohort study was used to analyze the clinical data of 46 patients with trimalleolar ankle fracture admitted to the First Affiliated Hospital of Naval Military Medical University from June 2013 to June 2019, including 14 males and 32 females, at age of 19-71 years [(49.2±14.9)years]. There were 33 patients with supination-external rotation type IV ankle fracture and 13 with pronation-external rotation type IV ankle fracture according to Lauge-Hansen classification. Open reduction and internal fixation was performed through the modified posterolateral approach combined with medial approach in 25 patients (modified approach group), and through the traditional posterolateral approach combined with medial approach in 21 patients (traditional approach group). The visual analogue score (VAS) at 3 days and 1 week after surgery, fracture healing time, range of ankle flexion and extension and Baird-Jackson score at the final follow-up and postoperative complications (numbness of the affect limb, wound necrosis, etc.) were compared between the two groups.Results:All patients were followed up for 11-21 months [(14.8±2.2)months]. There was no statistical difference in VAS or fracture healing time at 3 days after surgery between the two groups (all P>0.05). The VAS was 3.0 (3.0, 4.0)points in modified approach group at 1 week after surgery, significantly lower than 4.0 (3.0, 5.0)points in traditional approach group ( P<0.05). At the final follow-up, there was no statistical difference in range of ankle plantarflexion between the two groups ( P>0.05), but range of ankle dorsiflexion was significantly greater in modified approach group [(11.8±2.8)°] than that in traditional approach group [(8.1±3.5)°] ( P<0.01). At the final follow-up, Baird-Jackson score was not statistically different between the two groups ( P>0.05). There were 4 patients with numbness and 2 with wound necrosis in traditional approach group, but no numbness or wound necrosis occurred in modified approach group ( P<0.01). Conclusion:Both the modified posterolateral approach combined with medial approach and traditional posterolateral approach combined with medial approach can achieve good clinical results in open reduction and internal fixation of trimalleolar ankle fractures, but the former has advantages of better pain relief, better recovery of ankle dorsiflexion and less complications.
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Bone tissue repair has long been a hot topic and difficult issue in the field of regenerative medicine research. Although the rapid development of bone tissue engineering technology significantly accelerates the level of bone repair in recent years, bone regeneration research still faces many challenges such as difficulty in regeneration under pathological condition and unclear regenerative regulatory mechanisms. As a result, the evelopment of bone tissue engineering technology encounters a bottleneck, restricting more researches over bone regeneration and repair. As a novel concept, bone organoids are proposed and constructed in vitro with the help of tissue engineering technology based on biological theory, and can simulate the complex biological functions of bone in vivo. Bone organoids show broad application prospects in the research of bone regeneration, including elucidating regulatory regeneration mechanisms, screening biomaterials and promoting regeneration, etc. In this study, the authors preliminarily discuss the features, construction and value of bone organoids so as to provide new insight for the treatment of bone defect.
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Lower extremity deep vein thrombosis (DVT) is one of the main complications in patients with traumatic fractures, and for severe patients, the DVT can even affect arterial blood supply, resulting in insufficient limb blood supply. If the thrombus breaks off, pulmonary embolism may occur, with a high mortality. The treatment and rehabilitation strategies of thrombosis in patients with lower extremity fractures have its particularity. DVT in traumatic fractures patients has attracted extensive attention and been largely studied, and the measures for prevention and treatment of DVT are constantly developing. In recent years, a series of thrombosis prevention and treatment guidelines have been updated at home and abroad, but there are still many doubts about the prevention and treatment of DVT in patients with different traumatic fractures. Accordingly, on the basis of summarizing the latest evidence-based medical evidence at home and abroad and the clinical experience of the majority of experts, the authors summarize the clinical treatment and prevention protocols for DVT in patients with traumatic fractures, and make this consensus on the examination and assessment, treatment, prevention and preventive measures for DVT in patients with different fractures so as to provide a practicable approach suitable for China ′s national conditions and improve the prognosis and the life quality of patients.
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Osteoarthritis (OA) is the most common type of arthritis with no effective therapy. Subchondral bone and overlying articular cartilage are closely associated and function as "osteo-chondral unit" in the joint. Abnormal mechanical load leads to activated osteoclast activity and increased bone resorption in the subchondral bone, which is implicated in the onset of OA pathogenesis. Thus, inhibiting subchondral bone osteoclast activation could prevent OA onset. Betaine, isolated from the Lycii Radicis Cortex (LRC), has been demonstrated to exert anti-inflammatory, antifibrotic and antiangiogenic properties. Here, we evaluated the effects of betaine on anterior cruciate ligament transection (ACLT)-induced OA mice. We observed that betaine decreased the number of matrix metalloproteinase 13 (MMP-13)-positive and collagen X (Col X)-positive cells, prevented articular cartilage proteoglycan loss and lowered the OARSI score. Betaine decreased the thickness of calcified cartilage and increased the expression level of lubricin. Moreover, betaine normalized uncoupled subchondral bone remodeling as defined by lowered trabecular pattern factor (Tb.pf) and increased subchondral bone plate thickness (SBP). Additionally, aberrant angiogenesis in subchondral bone was blunted by betaine treatment. Mechanistically, we demonstrated that betaine suppressed osteoclastogenesis in vitro by inhibiting reactive oxygen species (ROS) production and subsequent mitogen-activated protein kinase (MAPK) signaling. These data demonstrated that betaine attenuated OA progression by inhibiting hyperactivated osteoclastogenesis and maintaining microarchitecture in subchondral bone.
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[This corrects the article DOI: 10.3389/fphar.2018.00022.].
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The osteoporotic fracture is characterized by a high disability rate，poor internal fixation strength，delayed bone healing，etc.，which greatly affects elderly health，so accelerating fracture healing is the key point of therapeutic strategies. Current researches mainly concentrate in bone formation acceleration and resorption inhibition，but the outcomes turn out to be unsatisfactory under the coupling of osteoblasts and osteoclasts. The accumulation of yellow adipose tissue in the medullary cavity is often arisen in patients with osteoporotic fractures，but its role and mechanism in bone metabolism remain unclear. Bone marrow adipocytes are differentiated from mesenchymal stromal cells and possess unique metabolic and secretory functions involving in energy metabolism，maintenance of hematopoietic microenvironment and regulation of bone metabolism balance. However，the role of bone marrow adipose tissue（BMAT）in osteoporotic fracture healing requires more elucidation. In this study，the authors discuss the key role and molecular mechanism of BMAT in the regulation of bone metabolism and homeostasis，aiming to provid new ideas and targets for the promotion of osteoporotic fracture healing.
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The osteoporotic fracture is characterized by difficult treatment and poor prognosis. The studies of bone biology show that bone microenvironment changes during osteoporotic fractures，such as changes in immune factors，abnormal chemotaxis and differentiation of mesenchymal stem cells（MSCs），decreased estrogen secretion and receptor down-regulation and decreased mechanical sensitivity，which affect the fracture healing process. Current studies have shown that by improving the phenotypic polarization of macrophages，enhancing the chemotactic osteogenic activity of MSCs，supplementing estrogen and improving the biomechanical properties of bone can remodel the balance of bone microenvironment，thereby effectively improve the bone quality. The authors explore the effect and mechanism of bone microenvironment on healing of osteoporotic fractures from the perspectives of changes in bone microenvironment and imbalance of bone microenvironment that affect fracture healing and methods of bone microenvironment reconstruction，so as to provide new ideas for clinical treatment of osteoporotic fractures.
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The osteoporotic fracture, also known as fragility fracture, occurs due to osteoporosis. With the acceleration of aging in China, the incidence of osteoporotic fracture increases rapidly, which causes significant changes in the spectrum of orthopedic trauma. The osteoporotic fracture has both the commonness and particularity of fracture, which poses challenges to orthopedic surgeons. Meanwhile, the fast improvement of interdisciplinary research and the advancement of basic research in bone metabolism have brought many opportunities to facilitate the treatment of osteoporotic fracture. The authors intend to illustrate the challenges and solutions during the treatment of osteoporotic fracture by elaborating the awareness, fracture assessment, drug development, implant design, postoperative rehabilitation and refracture prevention to establish an improved protocol for the therapy.
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Osteoporotic fractures have become major social problems threatening the health of the elderly population in China. Compared with conventional fractures, low bone mass, bone defect and retarded healing issues of osteoporotic fractures contribute to the difficulty in treatment and rehabilitation. Addressing major concerns in clinical settings, the "three in one" bone repair strategy focuses on anti-osteoporosis therapies, appropriate bone graft and fracture healing promotion. The authors summarize misunderstandings in diagnosis and treatment of osteoporotic fractures and repair strategies, expecting to improve prognosis and clinically standardize the treatments for osteoporotic fractures, to further improve therapeutic effect and living quality of the patients.
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The incidence of osteoporotic distal humeral fracture in the elderly is progressing in recent decade. Difficulty of reduction and poor internal fixation stability make osteoporotic distal humerus fractures become a challenging fracture type. Therefore, it is necessary to develop an individualized treatment plan based on the patient's condition and functional requirements. The authors discuss key questions in the treatment of osteoporotic distal humerus fracture in combination with current literatures and researches, so as to provide a reference for clinical diagnosis and treatment.
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Due to the aging population in China, the occurrence of osteoporotic fractures is surging. Osteoporotic fractures around the joints like wrist, hip or knee are usually more sophisticated, compared with those in vertebrae, causing more challenges in treatment and rehabilitation. When dealing with these cases, orthopedic surgeons should pay attention to systematic anti-osteoporosis therapy including medications like calcium supplement and bone metabolic regulation drugs. In addition, the bone quality of the patients and the implant stability should be considered during surgical procedures. Besides, the patients need to be guided to participate in early motions and weight-bearing exercises to gain better function and satisfactory recovery. The authors focus on the issues and strategies of anti-osteoporosis management, surgery protocol, early rehabilitation as well as long-term follow-up and prevention of the patients with periarticular osteoporotic fractures so as to provide references for clinical practices.
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Objective:To investigate the influences of anxiety on postoperative efficacy in elderly patients with complex proximal humerus fractures.Methods:A retrospective case control study was conducted to analyze the clinical data of 297 elderly patients with complex proximal humerus fractures admitted to 5 tertiary hospitals in Shanghai from January 2017 to December 2018. There were 121 males and 176 females, aged 65-85 years [(74.2±8.5)years]. The fracture types included Neer type III in 176 patients and Neer type IV in 121 patients. Two days after admission, patients were analyzed by self-rating anxiety scale (SAS) and anxiety factors questionnaire (participated by Shanghai Mental Health Center) and they were divided into anxiety group (SAS>35) and nonanxiety group (SAS≤35). Anxiety group included 68 patients, among which 7 had conservative treatments. Nonanxiety group contained 229 patients, among which 7 had conservative treatments. Both groups underwent with proximal reduction of humerus fractures accepted the operations. Operative patient in both groups underwent open reduction and plate fixation. The surgery rate and length of hospital stay were compared between groups. After 1 year of follow-up, Constant-Murley score was used to evaluate the effect of shoulder joint and dual-energy X-ray absorptiometry (DXA) was taken to observe the wrist joint bone mineral density. Postoperative complications were recorded.Results:All operative patients were followed up for 10-28 months, with an average of 13.6 months. The surgery rate was 89.7% (61/68) in anxiety group and 96.9% (222/229) in nonanxiety group ( P<0.05). The hospital stay was (6.8±3.4)days for non-surgery patients and (10.2±2.8)days for surgery patients in anxiety group and (4.2±1.6)days for non-surgery patients and (7.4±2.2)days for surgery patients in nonanxiety group ( P<0.05). In anxiety group and nonanxiety group, the excellent and good rate of Constant-Murley score was respective 75.4% (46/61) and 88.3% (196/222) and the wrist joint bone mineral density was respective (-3.1±0.5)SD and (-2.9±0.6)SD (both P<0.05). The incidence of complications was 8.2% (5/61) in anxiety group and 4.5% (10/222) in nonanxiety group ( P>0.05). Conclusions:Anxiety has a significant negative influence on the surgery rate, length of hospital stay, shoulder joint function, wrist joint bone mineral density. Intervention on anxiety in elderly patients with complex proximal humerus fractures should be valued attention by clinical orthopedic surgeons.
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TSCI have dyskinesia and sensory disturbance that can cause various life-threaten complications. The patients with traumatic spinal cord injury (TSCI), seriously affecting the quality of life of patients. Based on the epidemiology of TSCI and domestic and foreign literatures as well as expert investigations, this expert consensus reviews the definition, injury classification, rehabilitation assessment, rehabilitation strategies and rehabilitation measures of TSCI so as to provide early standardized rehabilitation treatment methods for TSCI.
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Objective:To investigate the efficacy of Hebert screw internal fixation of osteoporotic distal humeral coronary fractures in the elderly.Methods:A retrospective case series study was conducted to analyze the data of 26 elderly patients with osteoporotic distal humeral coronary fractures treated in Changhai Hospital from December 2011 to December 2018, including 3 males and 23 females aged 56-84 years (mean, 67.8 years). According to Bryan-Morrey classification, there were 7 patients with type I, 11 with type III, and 8 with type IV. All patients received open reduction and internal fixation. Among the 26 patients, 10 patients with simple humeral head fractures were treated with Hebert screw internal fixation, and 16 patients with humeral head fractures combined with humeral epicondyle fracture were treated with Hebert screw combined with humeral condyle miniplate. Operation time and intraoperative bleeding volume were recorded. At last follow-up, elbow range of motion were measured, and Mayo elbow performance score and visual analog scale (VAS) score were assessed. Meantime, complications were observed.Results:A total of 22 patients were followed up for 6-57 months (mean, 31.8 months). Intraoperative bleeding volume was 100 to 245 ml (mean, 126 ml) and operation time was 60 to 195 minutes (mean, 85 minutes). At last follow-up, the elbow joint flexion was (117.3±4.2)° and extension was (8.2±2.1)°. Mayo elbow performance score improved from preoperative 16.5 (12.8, 24.0)points to postoperative 85.0 (82.5, 92.3)points ( P<0.05). VAS was increased from preoperative (9.6±0.5)points to (2.3±0.2)points at latest follow-up( P<0.05). Two patients had elbow joint stiffness after operation and recovered after functional exercise. One patient had bone displacement when receiving rehabilitation care, which did not affect the function, and hence no further treatment was given. All patients had no infection or skin and soft tissue complications after surgery. Conclusions:For osteoporotic distal humeral coronary fractures in the elderly, Hebert screw internal fixation is effective in facilitating function recovery and relieving pain. When the fracture is combined with lateral humeral condyle fracture, additional plate fixation can be used for rigid stabilization.
