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Reduction-responsive nucleic acid nanocarrier-mediated miR-22 inhibition of PI3K/AKT pathway for the treatment of patient-derived tumor xenograft osteosarcoma

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Bioactive Materials 2023年第10期28卷 376-385页

作者： Dafu Chen Chengyue Lei Weifeng Liu Meiyu Shao Meizhou Sun Jianxun Guo Jingjing Cao Jing-Jun Nie Peng Luo Yuwen Luo Bingran Yu Renxian Wang Shun Duan Fu-Jian Xu Laboratory of Bone Tissue Engineering Beijing Laboratory of Biomedical MaterialsNational Center for OrthopaedicsBeijing Research Institute of Traumatology and OrthopaedicsBeijing Jishuitan HospitalBeijing100035China State Key Laboratory of Chemical Resource Engineering Key Lab of Biomedical Materials of Natural Macromolecules(Beijing University of Chemical Technology)Ministry of EducationBeijing Laboratory of Biomedical MaterialsBeijing University of Chemical TechnologyBeijing100029China Department of orthopaedic Oncology surgery Beijing Jishuitan HospitalPeking UniversityBeijing100035China JST Sarcopenia Research Centre Beijing Research Institute of Traumatology and OrthopaedicsBeijing Jishuitan HospitalBeijing100035China

miRNAs are important regulators of gene expression and play key roles in the development of cancer, including osteosarcoma. During the development of osteosarcoma, the expression of miR-22 is significantly downregulated, making miR-22 as a promising therapeutic target against osteosarcoma. To design and fabricate efficient delivery carriers of miR-22 into osteosarcoma cells, a hydroxyl-rich reduction-responsive cationic polymeric nanoparticle, TGIC-CA (TC), was developed in this work, which also enhanced the therapeutic effects of Volasertib on osteosarcoma. TC was prepared by the ring-opening reaction between amino and epoxy groups by one-pot method, which had the good complexing ability with nucleic acids, reduction-responsive degradability and gene transfection performance. TC/miR-22 combined with volasertib could inhibit proliferation, migration and promote apoptosis of osteosarcoma cells in vitro. The anti-tumor mechanisms were revealed as TC/ miR-22 and volasertib could inhibit the PI3K/Akt signaling pathway synergistically. Furthermore, this strategy showed outstanding tumor suppression performance in animal models of orthotopic osteosarcoma, especially in patient-derived chemo-resistant and chemo-intolerant patient-derived xenograft (PDX) models, which reduced the risk of tumor lung metastasis and overcame drug resistance. Therefore, it has great potential for efficient treatment of metastasis and drug resistance of osteosarcoma by the strategy of localized, sustained delivery of miR-22 using the cationic nanocarriers combined with non-traditional chemotherapy drugs.

关键词： Nucleic acid delivery Nanoparticle Gene therapy Osteosarcoma Responsive Patient-Derived Xenograft(PDX)

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Long-term results of olecranon fractures treated using the XS nail? system

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中华创伤杂志(英文版) 2022年第6期25卷 336-344页

作者： H?chtl-Lee Leonard Spalteholz Matthias Raven Tim Friedrich Moghaddam Arash Friedl Wilhelm Aschaffenburg Trauma and orthopaedic Research Group Center for orthopaedics Trauma surgery and Sports Medicine Hospital Aschaffenburg-Alzenau GGmbH Am Hasenkopf 1 Aschaffenburg Germany Center for orthopaedics and Trauma surgery Leipzig division of orthopaedics and Trauma surgery Rotkreuzklinik Wertheim GGmbH Wertheim Am Main

Purpose: Olecranon fractures are particularly vulnerable to distraction and subsequent fracture dislocation due to the high tensile forces. Surgical treatment aims at reducing the fracture and restoring the anatomical joint surface condition, as well as neutralizing the strain inhibiting fracture healing. The XS nail? (Intercus GmbH, Bad Blankenberg, Germany), an intramedullary implant exerting compression across the entire fracture surface, unlike plates, leaves a minimal extra-cortical profile, and can be secured with threaded locking wires, thereby retaining the anatomical reduction without displacement or steps within the articular surface, which was often found in tension band wiring. After encouraging initial results, the long-term outcome was assessed. Methods: This retrospective study evaluated the long-term outcome of patients surgically treated at our trauma center between January 2002 and December 2005 using the XS nail?. Patients over the age of 18 years eligible for the study must have undergone surgery for isolated, recent (less than 14 days) traumatic olecranon fractures, without concomitant injuries to the ipsilateral elbow and forearm. Further exclusion criteria were pseudarthrosis, re-fractures and osteotomy for distal humerus surgery, as well as polytraumatized patients unable to aid in their own recovery. Data were retrospectively gathered by standardised questionnaire and patient records, as well as surgery and anesthesiology reports. Data analysis was performed using Microsoft Office Excel? 2016. Results: There were 32 patients, 13 males (mean age 49.0 years) and 19 females (mean age 68.9 years) with 11 Schatzkers type D, 7 each type A and C, 5 type B and 2 type E at an average of 55.2 months, all showing complete consolidation. Of them, 6 patients had a loss of range of motion with more than 10° in the sagittal plane, and only 1 patient exceeded 10° reduction of supina

关键词： Olecranon fracture Intramedullary nail Treatment DASH XS nail

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Osteolysis in total hip arthroplasty in relation to metal ion release: Comparison between monolithic prostheses and different modularities

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World Journal of Orthopedics 2021年第10期12卷 768-780页

作者： Francesco Manfreda Egzon Bufi Enrico Francesco Florio Paolo Ceccarini Giuseppe Rinonapoli Auro Caraffa Pierluigi Antinolfi division of Orthopedics and Trauma surgery Santa Maria della Misericordia HospitalPerugia 06100Italy Department of Orthopedics and traumatology University of PerugiaPerugia 06100Italy Department of orthopaedic and traumatology Infermi HospitalAUSL RomagnaRimini 47921Italy Department of orthopaedic University of PerugiaPerugia 06100Italy

BACKGROUND Among the various complications associated with total hip arthroplasty(THA)periprosthetic osteolysis and wear phenomena due to the release of metal particles,are two of the most common and have been reported to be correlated because of inflammatory responses directed towards released particles that generally activate macrophagic osteolytic ***,new masses known as pseudotumors can appear in soft tissues around a prosthetic *** date,there is paucity of reliable data from studies investigating for any association between the above mentioned adverse *** To investigate for the existence of any association between serum and urine concentrations of metal-ions released in THA and periprosthetic osteolysis for modular neck and monolithic *** Overall,76 patients were divided into three groups according to the type of hip prosthesis implants:Monoblock,modular with metal head and modular with ceramic *** an average f-up of 4 years,we conducted a radiological evaluation in order to detect any area of osteolysis around the prosthesis of both the femur and the ***,serum and urinary tests were performed to assess the values of Chromium and Cobalt *** analysis was performed to determine any association between the ion release and *** For the 3 study groups,the monolithic,modular ceramic-headed and modular metal-headed implants had different incidences of osteolysis events,which were higher for the modular ***,the most serious of these(grade 3)were detected almost exclusively for the modular implants with metal heads.A mapping of the affected areas was performed revealing that the highest incidences of osteolysis were evidenced in the pertrochanteric region at the femur level,and in the supero-external region at the acetabular *** the evaluation of the release of metals-ions from wear processes,serum and urinary chromium and cobalt values were found to

关键词： Total hip arthroplasty Peri-prosthetic osteolysis Metal-ions Monolithic total hip arthroplasty Modular ceramic headed total hip arthroplasty Modular metallic headed total hip arthroplasty

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Peripheral nerve regeneration with conduits:use of vein tubes

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Neural Regeneration Research 2015年第4期10卷 529-533页

作者： Rodrigo Guerra Sabongi Marcela Fernandes Joao Baptista Gomes dos Santos Department of Orthopedics and traumatology Escola Paulista de MedicinaFederal University of Sao Paulo division of Hand surgery Department of Orthopedics and TraumatologyEscola Paulista de MedicinaFederal University of Sao Paulo

Treatment of peripheral nerve injuries remains a challenge to modern medicine due to the com-plexity of the neurobiological nerve regenerating process. There is a greater challenge when the transected nerve ends are not amenable to primary end-to-end tensionless neurorraphy. When facing a segmental nerve defect, great effort has been made to develop an alternative to the au-tologous nerve graft in order to circumvent morbidity at donor site, such as neuroma formation, scarring and permanent loss of function. Tubolization techniques have been developed to bridge nerve gaps and have been extensively studied in numerous experimental and clinical trials. The use of a conduit intends to act as a vehicle for moderation and modulation of the cellular and molecular ambience for nerve regeneration. Among several conduits, vein tubes were validated for clinical application with improving outcomes over the years. This article aims to address the investigation and treatment of segmental nerve injury and draw the current panorama on the use of vein tubes as an autogenous nerve conduit.

关键词： peripheral nerve injury nerve graft nerve conduit Wallerian degeneration neurotrophic factors veins autografts nerve regeneration

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Wrist joint moments of walker-assisted gait:a study of biomechanics and instrumentation

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仪器仪表学报 2007年第9期28卷 1537-1542页

作者： Ming Dong Wang Weijie Wan Baikun Hu Yong Department of Biomedical Engineering and Scientific Instrument Tianjin University Tianfin 300072 China Department of orthopaedic and Trauma surgery University of Dundee UK Department of orthopaedics and traumatology Hong Kong University Hong Kong SAR China

While walkers are commonly prescribed to improve patient stability and ambulatory ability,quantitative study of the biomechanical and functional requirements for effective walker use is *** investigate the changes in wrist joint moments that occur with the use of a standard walker,a strain gauge-based walker instrumentation sys- tem was developed for the measurement of wrist joint *** walker dynamometer was integrated with an up- per extremity biomechanical *** system data were collected for twelve healthy,right-handed young a- dults following informed *** upper extremity kinematic data were acquired with a six-camera motion a- nalysis *** joint moments at the wrist were determined in the three clinical planes using the inverse dy- namics *** showed that during a walker-assisted gait there were several typical demands of wrist abduc- tor,adductor,flexor and external *** interesting'bare phase'of wrist joint moments was also found in phase angle[-30°,30°]of gait *** description of wrist joint moments during walker-assisted gait may pro- vide insight into walker use parameters and rehabilitative strategies.

关键词：生物力学仪表助行器辅助步法桡腕关节矩

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A modified three-incision approach to treating three-column Lisfranc injuries

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Chinese Journal of traumatology 2022年第6期25卷 362-366页

作者： Ting-Hu Zhao Han-Xin Chen Bin Jia Yun-Bo Bai Jike Lu Wei Ren Department of Foot and Ankle Shen Zhen Ping Le Orthopaedic HospitalShenzhen518118Guangdong ProvinceChina Department of orthopaedic Trauma Shen Zhen Ping Le Orthopaedic HospitalShenzhen518118Guangdong ProvinceChina Department of Orthopedic surgery United Family HospitalBeijing100015China

Purpose:The most popular surgical approach to manage Lisfranc fracture-dislocations is the double-incision approach,which frequently causes a variety of complications,such as skin necrosis,rotational malreduction of the first tarsometatarsal joint(TMTJ)and lateral column dorsoplantar malreduction of the *** introduce a three-incision approach to treat Lisfranc fracture-dislocations with only minor postoperative complications and good foot ***:We prospectively selected 30 previously healthy patients,ranging from 18 to 60 years of age,but only 23 patients completed the follow-up and thus were finally included,with an average age of 38.1±12.9 *** patients have sustained Lisfranc fracture-dislocations involving all three-column;13.0%(3/23)were Myerson classification type A(medial),47.8%(11/23)were type A(lateral),and 39.1%(9/23)were type *** patients were treated via a three-incision approach:a long incision made along the lateral border of the second ray was used as a working incision to visualize and reduce the first three TMTJs,as well as to apply internal fixation instrumentation;a 2 cm medial incision was made at the medial side of the first TMTJ as an inspecting incision,ensuring good reduction of the first TMTJ in medial and plantar view;another 1 cm inspecting incision was made at the dorsal side of the fourth/fifth TMTJ to prevent sagittal subluxation of the lateral ***±SD was used for quantitative data such as operation time,follow-up time and foot function *** complications were documented,and foot function was evaluated using the American orthopaedic foot&ankle society score,foot function index and Maryland foot score at *** foot function of the injured foot and contralateral foot of the same patient was at the end of follow-up,and independent samplet-test was used for statistical ***:The median operation time was 117.9±14.6 min(range 93-142 min).All complications occurred within three

关键词： Surgical approach Three-incision approach Complication Three-column Lisfranc fracture-dislocation Foot function

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“Genetic scissors”CRISPR/Cas9 genome editing cutting-edge biocarrier technology for bone and cartilage repair

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Bioactive Materials 2023年第4期22卷 254-273页

作者： Chao Li Yawei Du Tongtong Zhang Haoran Wang Zhiyong Hou Yingze Zhang Wenguo Cui Wei Chen Department of orthopaedics The Third Hospital of Hebei Medical UniversityOrthopaedic Research Institution of Hebei ProvinceNHC Key Laboratory of Intelligent Orthopaedic EquipmentNo.139 Ziqiang RoadShijiazhuang050051PR China Department of orthopaedics Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint DiseasesShanghai Institute of Traumatology and OrthopaedicsRuijin HospitalShanghai Jiao Tong University School of Medicine197 Ruijin 2nd RoadShanghai200025PR China

CRISPR/Cas9 is a revolutionary genome editing technology with the tremendous advantages such as precisely targeting/shearing ability,low cost and convenient operation,becoming an efficient and indispensable tool in biological *** a disruptive technique,CRISPR/Cas9 genome editing has a great potential to realize a future breakthrough in the clinical bone and cartilage repairing as *** review highlights the research status of CRISPR/Cas9 system in bone and cartilage repair,illustrates its mechanism for promoting osteogenesis and chondrogenesis,and explores the development tendency of CRISPR/Cas9 in bone and cartilage repair to overcome the current limitations.

关键词： CRISPR/Cas9 Genome editing Bone repair Cartilage repair

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Total hip replacement:A meta-analysis to evaluate survival of cemented,cementless and hybrid implants

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World Journal of Orthopedics 2017年第2期8卷 192-207页

作者： Phedy Phedy H Dilogo Ismail Charles Hoo Yoshi P Djaja Departement of orthopaedic and traumatology Fatmawati General HospitalFaculty of Medicine Universities Indonesia Departement of orthopaedic and traumatology Ciptomangunkusumo General HospitalFaculty of Medicine Universities Indonesia

AIM To determine whether cemented, cementless, or hybrid implant was superior to the other in terms of survival *** Systematic searches across MEDLINE, CINAHL, and Cochrane that compared cemented, cementless and hybrid total hip replacement(THR) were performed. Two independent reviewers evaluated the risk ratios of revision due to any cause, aseptic loosening, infection, and dislocation rate of each implants with a pre-determined form. The risk ratios were pooled separately for clinical trials, cohorts and registers before pooled altogether using fixed-effect model. Meta-regressions were performed to identify the source of heterogeneity. Funnel plots were analyzed. RESULTS Twenty-seven studies comprising 5 clinical trials, 9 cohorts, and 13 registers fulfilled the research criteria and analyzed. Compared to cementless THR, cemented THR have pooled RR of 0.47(95%CI: 0.45-0.48), 0.9(0.84-0.95), 1.29(1.06-1.57) and 0.69(0.6-0.79) for revision due to any reason, revision due to aseptic loosening, revision due to infection, and dislocation respectively. Compared to hybrid THR, the pooled RRs of cemented THR were 0.82(0.76-0.89), 2.65(1.14-6.17), 0.98(0.7-1.38), and 0.67(0.57-0.79) respectively. Compared to hybrid THR, cementless THR had RRs of 0.7(0.65-0.75), 0.85(0.49-1.5), 1.47(0.93-2.34) and 1.13(0.98-1.3).CONCLUSION Despite the limitations in this study, there was some tendency that cemented fixation was still superior than other types of fixation in terms of implant survival.

关键词： Total hip replacement Implant survival Cemented Cementless Hybrid Meta-analysis

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IκB-ζsignaling promotes chondrocyte inflammatory phenotype,senescence,and erosive joint pathology

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Bone Research 2022年第1期10卷 195-211页

作者： Manoj Arra Gaurav Swarnkar Yael Alippe Gabriel Mbalaviele Yousef Abu-Amer Department of orthopaedic surgery and Cell Biology&Physiology Washington University School of MedicineSt.LouisMO 63110US Bone and Mineral division Department of MedicineWashington University School of MedicineSt.LouisMO 63110US Shriners Hospital for Children St.LouisMO 63110US.

Osteoarthritis is a joint disease characterized by a poorly-defined inflammatory response that does not encompass a massive immune cell infiltration yet contributes to cartilage degradation and loss of joint mobility, suggesting a chondrocyte intrinsic inflammatory response. Using primary chondrocytes from joints of osteoarthritic mice and patients, we first show that these cells express ample pro-inflammatory markers and RANKL in an NF-κB dependent manner. The inflammatory phenotype of chondrocytes was recapitulated by exposure of chondrocytes to IL-1β and bone particles, which were used to model bone matrix breakdown products revealed to be present in synovial fluid of OA patients, albeit their role was not defined. We further show that bone particles and IL-1β can promote senescent and apoptotic changes in primary chondrocytes due to oxidative stress from various cellular sources such as the mitochondria. Finally, we provide evidence that inflammation, oxidative stress and senescence converge upon IκB-ζ, the principal mediator downstream of NF-κB, which regulates expression of RANKL, inflammatory, catabolic,and SASP genes. Overall, this work highlights the capacity and mechanisms by which inflammatory cues, primarily joint degradation products, i.e., bone matrix particles in concert with IL-1β in the joint microenvironment, program chondrocytes into an “inflammatory phenotype” which inflects local tissue damage.

关键词： inflammatory IκB oxidative

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Military training-related abdominal injuries and diseases:Common types,prevention and treatment

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Chinese Journal of traumatology 2022年第4期25卷 187-192页

作者： Chuan Pang Zhi-Da Chen Bo Wei Wen-Tong Xu Hong-Qing Xi division of Abdominal Trauma surgery Department of General SurgeryFirst Medical Center of Chinese PLA General HospitalBeijing226010China

Military training is intense,difficult and often dangerous,so all kinds of injuries or diseases frequently occur during *** of the previous studies and reviews on military training-related injuries focused on musculoskeletal system,whereas there are no reviews of abdominal injuries and *** the incidence of military training-related abdominal injuries and diseases is relatively low,the patients’condition is often critical especially in the presence of abdominal organ injury,leading to multiorgan dysfunction syndrome and even *** paper elaborates on common types of military training-related abdominal injuries and diseases as well as the prevention and treatment measures,which provides some basis for scientific and reasonable training and improvement of medical security.

关键词： Military training Injuries Abdomen Prevention Treatment

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