The integrated repair of bone and cartilage boasts advantages for osteochondral restoration such as a long-term repair effect and less deterioration compared to repairing cartilage alone.Constructing multifactorial,sp...The integrated repair of bone and cartilage boasts advantages for osteochondral restoration such as a long-term repair effect and less deterioration compared to repairing cartilage alone.Constructing multifactorial,spatially oriented scaffolds to stimulate osteochondral regeneration,has immense significance.Herein,targeted drugs,namely kartogenin@polydopamine(KGN@PDA)nanoparticles for cartilage repair and miRNA@calcium phosphate(miRNA@CaP)NPs for bone regeneration,were in situ deposited on a patterned supramolecular-assembled 2-ureido-4[lH]-pyrimidinone(UPy)modified gelation hydrogel film,facilitated by the dynamic and responsive coordination and complexation of metal ions and their ligands.This hydrogel film can be rolled into a cylindrical plug,mimicking the Haversian canal structure of natural bone.The resultant hydrogel demonstrates stable mechanical properties,a self-healing ability,a high capability for reactive oxygen species capture,and controlled release of KGN and miR-26a.In vitro,KGN@PDA and miRNA@CaP promote chondrogenic and osteogenic differentiation of mesenchymal stem cells via the JNK/RUNX1 and GSK-3β/β-catenin pathways,respectively.In vivo,the osteochondral plug exhibits optimal subchondral bone and cartilage regeneration,evidenced by a significant increase in glycosaminoglycan and collagen accumulation in specific zones,along with the successful integration of neocartilage with subchondral bone.This biomaterial delivery approach represents a significant toward improved osteochondral repair.展开更多
BACKGROUND:Few contemporary studies have assessed physicians’knowledge of radiation exposure associated with common imaging studies,especially in trauma care.The purpose of this study was to assess the knowledge of p...BACKGROUND:Few contemporary studies have assessed physicians’knowledge of radiation exposure associated with common imaging studies,especially in trauma care.The purpose of this study was to assess the knowledge of physicians involved in caring for trauma patients regarding the effective radiation doses of musculoskeletal(MSK)imaging studies routinely utilized in the trauma setting.METHODS:An electronic survey was distributed to United States orthopaedic surgery,general surgery,and emergency medicine(EM)residency programs.Participants were asked to estimate the radiation dose for common imaging modalities of the pelvis,lumbar spine,and lower extremity,in terms of chest X-ray(CXR)equivalents.Physician estimates were compared to the true effective radiation doses.Additionally,participants were asked to report the frequency of discussing radiation risk with patients.RESULTS:A total of 218 physicians completed the survey;102(46.8%)were EM physicians,88(40.4%)wereorthopaedicsurgeons,and28(12.8%)weregeneralsurgeons.Physicians underestimated the effective radiation doses of nearly all imaging modalities,most notably for pelvic computed tomaography(CT)(median 50 CXR estimation vs.162 CXR actual)and lumbar CT(median 50 CXR estimation vs.638 CXR actual).There was no difference between physician specialties regarding estimation accuracy(P=0.133).Physicians who regularly discussed radiation risks with patients more accurately estimated radiation exposure(P=0.007).CONCLUSION:The knowledge among orthopaedic and general surgeons and EM physicians regarding the radiation exposure associated with common MSK trauma imaging is lacking.Further investigation with larger scale studies is warranted,and additional education in this area may improve care.展开更多
Surgery remains the standard treatment for spinal metastasis.However,uncontrolled intraoperative bleeding poses a significant challenge for adequate surgical resection and compromises surgical outcomes.In this study,w...Surgery remains the standard treatment for spinal metastasis.However,uncontrolled intraoperative bleeding poses a significant challenge for adequate surgical resection and compromises surgical outcomes.In this study,we develop a thrombin(Thr)-loaded nanorobothydrogel hybrid superstructure by incorporating nanorobots into regenerated silk fibroin nanofibril hydrogels.This superstructure with superior thixotropic properties is injected percutaneously and dispersed into the spinal metastasis of hepatocellular carcinoma(HCC)with easy bleeding characteristics,before spinal surgery in a mouse model.Under near-infrared irradiation,the self-motile nanorobots penetrate into the deep spinal tumor,releasing Thr in a controlled manner.Thr-induced thrombosis effectively blocks the tumor vasculature and reduces bleeding,inhibiting tumor growth and postoperative recurrence with Au nanorod-mediated photothermal therapy.Our minimally invasive treatment platform provides a novel preoperative therapeutic strategy for HCC spinal metastasis effectively controlling intraoperative bleeding and tumor growth,with potentially reduced surgical complications and enhanced operative outcomes.展开更多
Rheumatoid arthritis(RA)is a systemic autoimmune disease that is primarily manifested as synovitis and polyarticular opacity and typically leads to serious joint damage and irreversible disability,thus adversely affec...Rheumatoid arthritis(RA)is a systemic autoimmune disease that is primarily manifested as synovitis and polyarticular opacity and typically leads to serious joint damage and irreversible disability,thus adversely affecting locomotion ability and life quality.Consequently,good prognosis heavily relies on the early diagnosis and effective therapeutic monitoring of RA.Activatable fluorescent probes play vital roles in the detection and imaging of biomarkers for disease diagnosis and in vivo imaging.Herein,we review the fluorescent probes developed for the detection and imaging of RA biomarkers,namely reactive oxygen/nitrogen species(hypochlorous acid,peroxynitrite,hydroxyl radical,nitroxyl),pH,and cysteine,and address the related challenges and prospects to inspire the design of novel fluorescent probes and the improvement of their performance in RA studies.展开更多
Degenerative musculoskeletal diseases are structural and functional failures of the musculoskeletal system,including osteoarthritis,osteoporosis,intervertebral disc degeneration(IVDD),and sarcopenia.As the global popu...Degenerative musculoskeletal diseases are structural and functional failures of the musculoskeletal system,including osteoarthritis,osteoporosis,intervertebral disc degeneration(IVDD),and sarcopenia.As the global population ages,degenerative musculoskeletal diseases are becoming more prevalent.However,the pathogenesis of degenerative musculoskeletal diseases is not fully understood.Previous studies have revealed that endoplasmic reticulum(ER)stress is a stress response that occurs when impairment of the protein folding capacity of the ER leads to the accumulation of misfolded or unfolded proteins in the ER,contributing to degenerative musculoskeletal diseases.By affecting cartilage degeneration,synovitis,meniscal lesion,subchondral bone remodeling of osteoarthritis,bone remodeling and angiogenesis of osteoporosis,nucleus pulposus degeneration,annulus fibrosus rupture,cartilaginous endplate degeneration of IVDD,and sarcopenia,ER stress is involved in the pathogenesis of degenerative musculoskeletal diseases.Preclinical studies have found that regulation of ER stress can delay the progression of multiple degenerative musculoskeletal diseases.These pilot studies provide foundations for further evaluation of the feasibility,efficacy,and safety of ER stress modulators in the treatment of musculoskeletal degenerative diseases in clinical trials.In this review,we have integrated up-to-date research findings of ER stress into the pathogenesis of degenerative musculoskeletal diseases.In a future perspective,we have also discussed possible directions of ER stress in the investigation of degenerative musculoskeletal disease,potential therapeutic strategies for degenerative musculoskeletal diseases using ER stress modulators,as well as underlying challenges and obstacles in bench-to-beside research.展开更多
Early surgical resection and chemotherapy of bone cancer are commonly used in the treatment of bone tumor,but it is still highly challenging to prevent recurrence and fill the bone defect caused by the resection site....Early surgical resection and chemotherapy of bone cancer are commonly used in the treatment of bone tumor,but it is still highly challenging to prevent recurrence and fill the bone defect caused by the resection site.In this work,we report a rational integration of photonic-responsive two-dimensional(2D)ultrathin niobium carbide(Nb2C)MXene nanosheets(NSs)into the 3D-printed bone-mimetic scaffolds(NBGS)for osteosarcoma treatment.The integrated 2D Nb2C-MXene NSs feature specific photonic response in the second near-infrared(NIR-II)biowindow with high tissue-penetrating depth,making it highly efficient in killing bone cancer cells.Importantly,Nb-based species released by the biodegradation of Nb2C MXene can obviously promote the neogenesis and migration of blood vessels in the defect site,which can transport more oxygen,vitamins and energy around the bone defect for the reparative process,and gather more immune cells around the defect site to accelerate the degradation of NBGS.The degradation of NBGS provides sufficient space for the bone remodeling.Besides,calcium and phosphate released during the degradation of the scaffold can promote the mineralization of new bone tissue.The intrinsic multifunctionality of killing bone tumor cell and promoting angiogenesis and bone regeneration makes the engineered Nb2C MXeneintegrated composite scaffolds a distinctive implanting biomaterial on the efficient treatment of bone tumor.展开更多
PRIMARY synovial chondromatosis is a rarecondition in which foci of cartilage develop in thesynovial membrane of joints, bursae and tendonsheaths. It typically involves a single large jointin a young adult male.1 The ...PRIMARY synovial chondromatosis is a rarecondition in which foci of cartilage develop in thesynovial membrane of joints, bursae and tendonsheaths. It typically involves a single large jointin a young adult male.1 The ectopic foci of cartilage canresult in painful joint effusion, and the generation of loosebodies can cause mechanical symptoms.2,3 The etiology ofprimary synovial chondromatosis remains unknown, butmetaplastic theory is the most popular hypothesis. Thecommonly involved joints are knee, elbow, and hip.^4 Theshoulder is a rare site of synovial chondromatosis2,3,5 andthe extra-articular involvement even rarer, with only fewcases presented in literature. This report presents a rarecase of primary combined intra-articular andextra-articular synovial chondromatosis of shoulder jointtreated with arthroscopy.展开更多
The original version of this article unfortunately contain some mistakes in figure.The authors found that the curves in Fig.1f,g were missing.The corrected version of Fig.1 is given below:Fig.1 Fabrication and charact...The original version of this article unfortunately contain some mistakes in figure.The authors found that the curves in Fig.1f,g were missing.The corrected version of Fig.1 is given below:Fig.1 Fabrication and characterization of ultrathin 2D Nb2C MXene NSs.a,b SEM images of Nb2AlC ceramics with corresponding element mapping(Nb,Al and C).c,d SEM images of multilayered Nb2C MXene and the corresponding element mapping(Nb,Al and C).展开更多
Essential proteins are crucial for biological processes and can be identified through both experimental and computational methods.While experimental approaches are highly accurate,they often demand extensive time and ...Essential proteins are crucial for biological processes and can be identified through both experimental and computational methods.While experimental approaches are highly accurate,they often demand extensive time and resources.To address these challenges,we present a computational ensemble learning framework designed to identify essential proteins more efficiently.Our method begins by using node2vec to transform proteins in the protein–protein interaction(PPI)network into continuous,low-dimensional vectors.We also extract a range of features from protein sequences,including graph-theory-based,information-based,compositional,and physiochemical attributes.Additionally,we leverage deep learning techniques to analyze high-dimensional position-specific scoring matrices(PSSMs)and capture evolutionary information.We then combine these features for classification using various machine learning algorithms.To enhance performance,we integrate the outputs of these algorithms through ensemble methods such as voting,weighted averaging,and stacking.This approach effectively addresses data imbalances and improves both robustness and accuracy.Our ensemble learning framework achieves an AUC of 0.960 and an accuracy of 0.9252,outperforming other computational methods.These results demonstrate the effectiveness of our approach in accurately identifying essential proteins and highlight its superior feature extraction capabilities.展开更多
EXTRASKELETAL chondroma is a rare benigntumor that usually develops in the soft tissue,which commonly occurs in the limbs of adults andgenerally presents as painless masses without thesurrounding tissues involvement. ...EXTRASKELETAL chondroma is a rare benigntumor that usually develops in the soft tissue,which commonly occurs in the limbs of adults andgenerally presents as painless masses without thesurrounding tissues involvement. The diagnosis mainlydepends on computed tomography, magnetic resonanceimaging （MRI） examination, and postoperative pathologicalexamination. This paper reports a case of extraskeletalchondroma in the popliteal region.展开更多
Objective To construct adeno-associated virus (AAV) expression system for transforming growth factor β3 (TGFβ3) and detect its biological effect on proteoglycan synthesis of the earlier and later dedifferentiated ra...Objective To construct adeno-associated virus (AAV) expression system for transforming growth factor β3 (TGFβ3) and detect its biological effect on proteoglycan synthesis of the earlier and later dedifferentiated rabbit lumbar disc nucleus pulpous (NP) cells, which was compared with that of adenovirus (AV) expression system for TGFβ1. Methods TGFβ3 gene was obtained using PCR. Its upstream contained restriction enzyme site Kpn Ⅰ, and its downstream contained restriction enzyme site SalⅠ. Using the restriction enzyme sites of PCR product of TGFβ3 and the corresponding multiple cloning site (MCS) in plasmid AAV, TGFβ3 was subcloned into AAV. The recombinant plasmid AAV-TGFβ3 was transfected into H293 cells with LipofectamineTM 2000, and the expression of TGFβ3 gene was detected using immunofluorescent analysis. After AAV-TGFβ3 virus particle with infectious activity was packaged, TGFβ3 expression in NP cells was detected by immunoblotting, and its biological effect on proteoglycan synthesis was detected by antonopulos method and compared with that of AV-TGFβ1 in the earlier and later dedifferentiated NP cells. Results For the earlier dedifferentiated NP cells, AAV-TGFβ3 slowly and stably enhanced proteoglycan synthesis, but AV-TGFβ1 rapidly and transiently enhanced its synthesis. For the later dedifferentiated NP cells, AAV-TGFβ3 stably enhanced proteoglycan synthesis, but AV-TGFβ1 inhibited its synthesis. Conclusion AAV expression system can mediate TGFβ3 gene to be expressed stably, and AAV-TGFβ3 can enhance proteoglycan synthesis of the earlier and later dedifferentiated NP cells.展开更多
Background: The purpose of this study was to compare the frequency of femoroacetabular impingement(FAI) between matched groups of military veterans and civilian patients with end-stage hip osteoarthritis(OA).Methods: ...Background: The purpose of this study was to compare the frequency of femoroacetabular impingement(FAI) between matched groups of military veterans and civilian patients with end-stage hip osteoarthritis(OA).Methods: Patients who underwent a primary total hip arthroplasty(THA) between January 1, 2015 and December 31, 2015 at a single Veteran’s Affairs Hospital were identified. Veterans were then matched 1:2 with civilian patients from our prospective outcome registry. The alpha angle and lateral center-edge angle(LCEA) were measured by a single evaluator. Independent t-tests were used to compare joint angles, and Fisher exact tests were used to compare the prevalence of cam(alpha angle ≥60°), pincer(LCEA ≥40°), or mixed-type pathologies.Results: Twenty-one veterans were matched 1:2 with civilian patients. The mean alpha angle did not significantly differ between groups(P=0.33) nor did the prevalence of cam deformities(P=0.79). The LCEAs were significantly greater in veterans than in civilians(P=0.04), and veterans also demonstrated a significantly greater prevalence of pincer and mixed-type deformities than civilians(P=0.025 and P=0.004, respectively).Conclusions: These results suggest that FAI is perhaps a more common mechanism in the progression of OA in a veteran population than in a civilian population, as pincer and mixed-type deformities were significantly more common among veterans than civilians. The forces borne by the hip during military training exceed normal physiologic conditions. In addition, the time between symptom onset and surgical correction may be 10–12 months longer for active military personnel than for civilians. The combination of increased physical demands and a protracted time to treatment highlights the need for better recognition of FAI in military members. Future studies are necessary to determine whether earlier intervention may prevent or delay the progression to end-stage OA and the need for total hip arthroplasty.展开更多
Objective. To introduce a new spinal internal fixation system, Texas Scottish Rite Hospital (TSRH), and to investigate its early clinical outcomes.Methods. The preliminary clinical outcomes of 15 patients with thoraco...Objective. To introduce a new spinal internal fixation system, Texas Scottish Rite Hospital (TSRH), and to investigate its early clinical outcomes.Methods. The preliminary clinical outcomes of 15 patients with thoracolumbar or lumbar scoliosis treated by anterior spinal fusion with TSRH instrumentation were studied retrospectively. Fourteen patients were diagnosed as idiopathic scoliosis and 1 as neuromuscular scoliosis.Results. Preoperatively, the Cobb's angle on the coronal plane was 55. 8° (range 35° - 78°), and 14° postoperatively, with an average correction of 74. 8 %. The average unfused thoracical curve was 35. 9 ° preoperatively (range 26° - 51°) and 21. 8° (10°-42° ) postoperatively, with 40% correction. The sagittal curve of lumbar was kept physiologically, preoperative 27. 9° and postoperative 25. 7° respectively. The trunk shift was 13.4 mm (5 - 28mm) preoperatively and 3. 5 mm (0-7 mm) postoperatively. The averaged apic vertebra derivation was 47. 8 mm (21 - 69 mm) before operation and 10. 8 mm (3-20 mm) after operation. The distance of C7 to center sacrum vertical line (CSVL) was 19. 5 mm(16 - 42)preoperatively and 11. 3 mm (0-32 mm) postoperatively. The apical vertebra rotation was 3 degree in 15 patients preoperatively, and were improved to normal in 10 patients, 1 degree in 4 patients, and 2 degree in 1 patients postoperatively. None had neurological injury and infection. Only 1 patient complained a cool feeling in the low extremity of concave side, and the symptom vanished at 3-month followed up.Conclusion. If used appropriately, TSRH anterior spinal system is a good treatment for low thoracic or thoracic lumbar scoliosis.展开更多
Objective:To introduce a key-vertebral-screws technique(KVST) in the surgical treatment of scoliosis extending to main thoracic levels, and to find the role of fulcrum bending in predicting the result of surgical trea...Objective:To introduce a key-vertebral-screws technique(KVST) in the surgical treatment of scoliosis extending to main thoracic levels, and to find the role of fulcrum bending in predicting the result of surgical treatment for scoliosis by this technique. Methods: Seventeen consecutive patients with scoliosis extending to main thoracic spine,who underwent pure posterior fusion without anterior or posterior release by KVST between January 2004 and July 2005 were evaluated for fulcrum bending flexibility, surgical correction rate, fulcrum bending correction index (FBCI) in main thoracic curves. Universal Spine System (USS) instrumentation was used in 15 cases,Monarch in another 2 cases. The severity of the curves was measured by Cobb's method using Rad Work 6. 0 software. Preoperative standing AP radiographs, preoperative fulcrum bending anterioposterior (AP) radiographs, postoperative standing AP radiographs, and most recent follow-up standing AP radiographs for spine were measured and recorded. All the data were analyzed with two-sample paired t-test by Origin 7. 0 software. Results: Infection and neurological complications were not noted. No major complications were found. Just one case had some axial back pain, which got a full recovery from physiotherapy for 2 weeks. In the X-ray, there was an average correction of 71. 5% of the fused main thoracic curves, which had no significant lose of correction in final follow-up. For the whole fused main thoracic curves, the fulcrum bending flexibility were lower to operation correction rate (P = 0. 013). The average FBCI was 123%. From the data, the more rigid curves (especially fulcrum bending flexibility <50%), the more correction rate operation could get, compared with fulcrum bending flexibility. Conclusion: (1) KVST is a good method in the surgical treatment of thoracic scoliosis, which can get satisfying result with lower medical cost. (2) Fulcrum bending flexibility is lower than operative correction rate by KVST in main thoracic curves (P<0. 05). In the more rigid curves assessed by fulcrum-bending radiograph, the operative corrective could be gained, especially in the curves which FBCI is lower than 50%.展开更多
Objective: To identify eukaryotic expression vector of human bone morphogenetic protein 2 pcDNA3/BMP2, verify its expression in transfected human mesenchymal stem cells (hMSCs) and the effect on hMSCs differentiation....Objective: To identify eukaryotic expression vector of human bone morphogenetic protein 2 pcDNA3/BMP2, verify its expression in transfected human mesenchymal stem cells (hMSCs) and the effect on hMSCs differentiation. Methods: The BMP2 gene was cloned into a eukaryotic expression vector pcDNA3. Transfected the recombinant into hMSCs by liposome. Immunnohistochemistry and in situ hybridization methods were used to identify the expression of BMP2 mRNA and protein; ALP and Von Kossa stains were performed to identify the BMP2 gene differentiated effect on the hMSCs. Results: The pcDNA3/BMP2 fragments were as large as theory. BMP2 mRNA and protein were expressed and synthesized both in 48 h and 4 weeks after transfection, the ALP and Ca deposit exhibition, which marked the osteogenic lineage of hMSCs, were enhanced and sped. Conclusion: Transfection of pcDNA3/BMP2 is able to provide transient and persistent expression in hMSCs, and promote the MSCs differentiation to osteogenic lineage.展开更多
基金the Natural Science Foundation of China(Grant Nos.82072413,82101649)National Key Research and Development Program of China(Grant Nos.2021YFE0105400).
文摘The integrated repair of bone and cartilage boasts advantages for osteochondral restoration such as a long-term repair effect and less deterioration compared to repairing cartilage alone.Constructing multifactorial,spatially oriented scaffolds to stimulate osteochondral regeneration,has immense significance.Herein,targeted drugs,namely kartogenin@polydopamine(KGN@PDA)nanoparticles for cartilage repair and miRNA@calcium phosphate(miRNA@CaP)NPs for bone regeneration,were in situ deposited on a patterned supramolecular-assembled 2-ureido-4[lH]-pyrimidinone(UPy)modified gelation hydrogel film,facilitated by the dynamic and responsive coordination and complexation of metal ions and their ligands.This hydrogel film can be rolled into a cylindrical plug,mimicking the Haversian canal structure of natural bone.The resultant hydrogel demonstrates stable mechanical properties,a self-healing ability,a high capability for reactive oxygen species capture,and controlled release of KGN and miR-26a.In vitro,KGN@PDA and miRNA@CaP promote chondrogenic and osteogenic differentiation of mesenchymal stem cells via the JNK/RUNX1 and GSK-3β/β-catenin pathways,respectively.In vivo,the osteochondral plug exhibits optimal subchondral bone and cartilage regeneration,evidenced by a significant increase in glycosaminoglycan and collagen accumulation in specific zones,along with the successful integration of neocartilage with subchondral bone.This biomaterial delivery approach represents a significant toward improved osteochondral repair.
文摘BACKGROUND:Few contemporary studies have assessed physicians’knowledge of radiation exposure associated with common imaging studies,especially in trauma care.The purpose of this study was to assess the knowledge of physicians involved in caring for trauma patients regarding the effective radiation doses of musculoskeletal(MSK)imaging studies routinely utilized in the trauma setting.METHODS:An electronic survey was distributed to United States orthopaedic surgery,general surgery,and emergency medicine(EM)residency programs.Participants were asked to estimate the radiation dose for common imaging modalities of the pelvis,lumbar spine,and lower extremity,in terms of chest X-ray(CXR)equivalents.Physician estimates were compared to the true effective radiation doses.Additionally,participants were asked to report the frequency of discussing radiation risk with patients.RESULTS:A total of 218 physicians completed the survey;102(46.8%)were EM physicians,88(40.4%)wereorthopaedicsurgeons,and28(12.8%)weregeneralsurgeons.Physicians underestimated the effective radiation doses of nearly all imaging modalities,most notably for pelvic computed tomaography(CT)(median 50 CXR estimation vs.162 CXR actual)and lumbar CT(median 50 CXR estimation vs.638 CXR actual).There was no difference between physician specialties regarding estimation accuracy(P=0.133).Physicians who regularly discussed radiation risks with patients more accurately estimated radiation exposure(P=0.007).CONCLUSION:The knowledge among orthopaedic and general surgeons and EM physicians regarding the radiation exposure associated with common MSK trauma imaging is lacking.Further investigation with larger scale studies is warranted,and additional education in this area may improve care.
基金supported by the National Natural Science Foundation of China(No.52103171,82172738,82272457,22305044)China Postdoctoral Science Foundation(2023M730638)+3 种基金“Technology Innovation Action Plan”of Science and Technology Commission of Shanghai Municipality(21S11902700)Natural Science Foundation of Shanghai(21ZR1412300),Shanghai Science and Technology program(23Y31900202,23010502600)Shanghai“Rising Stars of Medical Talent”Youth Development Program(Youth Medical Talents-Specialist Program,[2020]087)Medical Engineering fund of Fudan University(yg2023-27).
文摘Surgery remains the standard treatment for spinal metastasis.However,uncontrolled intraoperative bleeding poses a significant challenge for adequate surgical resection and compromises surgical outcomes.In this study,we develop a thrombin(Thr)-loaded nanorobothydrogel hybrid superstructure by incorporating nanorobots into regenerated silk fibroin nanofibril hydrogels.This superstructure with superior thixotropic properties is injected percutaneously and dispersed into the spinal metastasis of hepatocellular carcinoma(HCC)with easy bleeding characteristics,before spinal surgery in a mouse model.Under near-infrared irradiation,the self-motile nanorobots penetrate into the deep spinal tumor,releasing Thr in a controlled manner.Thr-induced thrombosis effectively blocks the tumor vasculature and reduces bleeding,inhibiting tumor growth and postoperative recurrence with Au nanorod-mediated photothermal therapy.Our minimally invasive treatment platform provides a novel preoperative therapeutic strategy for HCC spinal metastasis effectively controlling intraoperative bleeding and tumor growth,with potentially reduced surgical complications and enhanced operative outcomes.
基金supported by the National Natural Science Foundation of China(82072432)the China-Japan Friendship Hospital Horizontal Project/Spontaneous Research Funding(2022-HX-JC-7)+1 种基金the National High Level Hospital Clinical Research Funding(2022-NHLHCRF-PY-20)the Elite Medical Professionals project of China-Japan Friendship Hospital(ZRJY2021-GG12).
文摘Rheumatoid arthritis(RA)is a systemic autoimmune disease that is primarily manifested as synovitis and polyarticular opacity and typically leads to serious joint damage and irreversible disability,thus adversely affecting locomotion ability and life quality.Consequently,good prognosis heavily relies on the early diagnosis and effective therapeutic monitoring of RA.Activatable fluorescent probes play vital roles in the detection and imaging of biomarkers for disease diagnosis and in vivo imaging.Herein,we review the fluorescent probes developed for the detection and imaging of RA biomarkers,namely reactive oxygen/nitrogen species(hypochlorous acid,peroxynitrite,hydroxyl radical,nitroxyl),pH,and cysteine,and address the related challenges and prospects to inspire the design of novel fluorescent probes and the improvement of their performance in RA studies.
基金supported by the National Natural Science Foundation of China(92268115,82072506,81874030,82172387,82372371,82371989)the Science and Technology Innovation Program of Hunan Province(2021RC3025)+3 种基金the Natural Science Foundation of Jiangsu Province(BK20230066)the Suzhou Science and Technology Development Plan(SKY2023035,SZM2023008)the Gusu Health Talents Program(GSWS2020023)the Innovation Project for Postgraduate Students of Central South University(1053320221391,1053320231273).
文摘Degenerative musculoskeletal diseases are structural and functional failures of the musculoskeletal system,including osteoarthritis,osteoporosis,intervertebral disc degeneration(IVDD),and sarcopenia.As the global population ages,degenerative musculoskeletal diseases are becoming more prevalent.However,the pathogenesis of degenerative musculoskeletal diseases is not fully understood.Previous studies have revealed that endoplasmic reticulum(ER)stress is a stress response that occurs when impairment of the protein folding capacity of the ER leads to the accumulation of misfolded or unfolded proteins in the ER,contributing to degenerative musculoskeletal diseases.By affecting cartilage degeneration,synovitis,meniscal lesion,subchondral bone remodeling of osteoarthritis,bone remodeling and angiogenesis of osteoporosis,nucleus pulposus degeneration,annulus fibrosus rupture,cartilaginous endplate degeneration of IVDD,and sarcopenia,ER stress is involved in the pathogenesis of degenerative musculoskeletal diseases.Preclinical studies have found that regulation of ER stress can delay the progression of multiple degenerative musculoskeletal diseases.These pilot studies provide foundations for further evaluation of the feasibility,efficacy,and safety of ER stress modulators in the treatment of musculoskeletal degenerative diseases in clinical trials.In this review,we have integrated up-to-date research findings of ER stress into the pathogenesis of degenerative musculoskeletal diseases.In a future perspective,we have also discussed possible directions of ER stress in the investigation of degenerative musculoskeletal disease,potential therapeutic strategies for degenerative musculoskeletal diseases using ER stress modulators,as well as underlying challenges and obstacles in bench-to-beside research.
基金the financial support from the National Key R&D Program of China(Grant No.2016YFA0203700)the National Natural Science Foundation of China(Grant Nos.51872185,51722211,51672303,81672131,81672143,82072417 and 81802247)+2 种基金the Program of Shanghai Academic Research Leader(Grant No.18XD1404300)the National Key Research and Development Project of China(Grant No.2018YFC1106303)the Science and Technology Commission of Shanghai Municipality(Grant No.17060502400).
文摘Early surgical resection and chemotherapy of bone cancer are commonly used in the treatment of bone tumor,but it is still highly challenging to prevent recurrence and fill the bone defect caused by the resection site.In this work,we report a rational integration of photonic-responsive two-dimensional(2D)ultrathin niobium carbide(Nb2C)MXene nanosheets(NSs)into the 3D-printed bone-mimetic scaffolds(NBGS)for osteosarcoma treatment.The integrated 2D Nb2C-MXene NSs feature specific photonic response in the second near-infrared(NIR-II)biowindow with high tissue-penetrating depth,making it highly efficient in killing bone cancer cells.Importantly,Nb-based species released by the biodegradation of Nb2C MXene can obviously promote the neogenesis and migration of blood vessels in the defect site,which can transport more oxygen,vitamins and energy around the bone defect for the reparative process,and gather more immune cells around the defect site to accelerate the degradation of NBGS.The degradation of NBGS provides sufficient space for the bone remodeling.Besides,calcium and phosphate released during the degradation of the scaffold can promote the mineralization of new bone tissue.The intrinsic multifunctionality of killing bone tumor cell and promoting angiogenesis and bone regeneration makes the engineered Nb2C MXeneintegrated composite scaffolds a distinctive implanting biomaterial on the efficient treatment of bone tumor.
文摘PRIMARY synovial chondromatosis is a rarecondition in which foci of cartilage develop in thesynovial membrane of joints, bursae and tendonsheaths. It typically involves a single large jointin a young adult male.1 The ectopic foci of cartilage canresult in painful joint effusion, and the generation of loosebodies can cause mechanical symptoms.2,3 The etiology ofprimary synovial chondromatosis remains unknown, butmetaplastic theory is the most popular hypothesis. Thecommonly involved joints are knee, elbow, and hip.^4 Theshoulder is a rare site of synovial chondromatosis2,3,5 andthe extra-articular involvement even rarer, with only fewcases presented in literature. This report presents a rarecase of primary combined intra-articular andextra-articular synovial chondromatosis of shoulder jointtreated with arthroscopy.
文摘The original version of this article unfortunately contain some mistakes in figure.The authors found that the curves in Fig.1f,g were missing.The corrected version of Fig.1 is given below:Fig.1 Fabrication and characterization of ultrathin 2D Nb2C MXene NSs.a,b SEM images of Nb2AlC ceramics with corresponding element mapping(Nb,Al and C).c,d SEM images of multilayered Nb2C MXene and the corresponding element mapping(Nb,Al and C).
基金financially supported by the National Key R&D Program of China(Grant No.2022YFF1202600)the National Natural Science Foundation of China(Grant No.82301158)+4 种基金Science and Technology Innovation Action Plan of Shanghai Science and Technology Committee(Grant No.22015820100)Two-hundred Talent Support(Grant No.20152224)Translational Medicine Innovation Project of Shanghai Jiao Tong University School of Medicine(Grant No.TM201915)Clinical Research Project of Multi-Disciplinary Team,Shanghai Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine(Grant No.201914)China Postdoctoral Science Foundation(Grant No.2023M742332)。
文摘Essential proteins are crucial for biological processes and can be identified through both experimental and computational methods.While experimental approaches are highly accurate,they often demand extensive time and resources.To address these challenges,we present a computational ensemble learning framework designed to identify essential proteins more efficiently.Our method begins by using node2vec to transform proteins in the protein–protein interaction(PPI)network into continuous,low-dimensional vectors.We also extract a range of features from protein sequences,including graph-theory-based,information-based,compositional,and physiochemical attributes.Additionally,we leverage deep learning techniques to analyze high-dimensional position-specific scoring matrices(PSSMs)and capture evolutionary information.We then combine these features for classification using various machine learning algorithms.To enhance performance,we integrate the outputs of these algorithms through ensemble methods such as voting,weighted averaging,and stacking.This approach effectively addresses data imbalances and improves both robustness and accuracy.Our ensemble learning framework achieves an AUC of 0.960 and an accuracy of 0.9252,outperforming other computational methods.These results demonstrate the effectiveness of our approach in accurately identifying essential proteins and highlight its superior feature extraction capabilities.
文摘EXTRASKELETAL chondroma is a rare benigntumor that usually develops in the soft tissue,which commonly occurs in the limbs of adults andgenerally presents as painless masses without thesurrounding tissues involvement. The diagnosis mainlydepends on computed tomography, magnetic resonanceimaging （MRI） examination, and postoperative pathologicalexamination. This paper reports a case of extraskeletalchondroma in the popliteal region.
基金Supported by the National Natural Sciences Foundation of China(30271318).
文摘Objective To construct adeno-associated virus (AAV) expression system for transforming growth factor β3 (TGFβ3) and detect its biological effect on proteoglycan synthesis of the earlier and later dedifferentiated rabbit lumbar disc nucleus pulpous (NP) cells, which was compared with that of adenovirus (AV) expression system for TGFβ1. Methods TGFβ3 gene was obtained using PCR. Its upstream contained restriction enzyme site Kpn Ⅰ, and its downstream contained restriction enzyme site SalⅠ. Using the restriction enzyme sites of PCR product of TGFβ3 and the corresponding multiple cloning site (MCS) in plasmid AAV, TGFβ3 was subcloned into AAV. The recombinant plasmid AAV-TGFβ3 was transfected into H293 cells with LipofectamineTM 2000, and the expression of TGFβ3 gene was detected using immunofluorescent analysis. After AAV-TGFβ3 virus particle with infectious activity was packaged, TGFβ3 expression in NP cells was detected by immunoblotting, and its biological effect on proteoglycan synthesis was detected by antonopulos method and compared with that of AV-TGFβ1 in the earlier and later dedifferentiated NP cells. Results For the earlier dedifferentiated NP cells, AAV-TGFβ3 slowly and stably enhanced proteoglycan synthesis, but AV-TGFβ1 rapidly and transiently enhanced its synthesis. For the later dedifferentiated NP cells, AAV-TGFβ3 stably enhanced proteoglycan synthesis, but AV-TGFβ1 inhibited its synthesis. Conclusion AAV expression system can mediate TGFβ3 gene to be expressed stably, and AAV-TGFβ3 can enhance proteoglycan synthesis of the earlier and later dedifferentiated NP cells.
文摘Background: The purpose of this study was to compare the frequency of femoroacetabular impingement(FAI) between matched groups of military veterans and civilian patients with end-stage hip osteoarthritis(OA).Methods: Patients who underwent a primary total hip arthroplasty(THA) between January 1, 2015 and December 31, 2015 at a single Veteran’s Affairs Hospital were identified. Veterans were then matched 1:2 with civilian patients from our prospective outcome registry. The alpha angle and lateral center-edge angle(LCEA) were measured by a single evaluator. Independent t-tests were used to compare joint angles, and Fisher exact tests were used to compare the prevalence of cam(alpha angle ≥60°), pincer(LCEA ≥40°), or mixed-type pathologies.Results: Twenty-one veterans were matched 1:2 with civilian patients. The mean alpha angle did not significantly differ between groups(P=0.33) nor did the prevalence of cam deformities(P=0.79). The LCEAs were significantly greater in veterans than in civilians(P=0.04), and veterans also demonstrated a significantly greater prevalence of pincer and mixed-type deformities than civilians(P=0.025 and P=0.004, respectively).Conclusions: These results suggest that FAI is perhaps a more common mechanism in the progression of OA in a veteran population than in a civilian population, as pincer and mixed-type deformities were significantly more common among veterans than civilians. The forces borne by the hip during military training exceed normal physiologic conditions. In addition, the time between symptom onset and surgical correction may be 10–12 months longer for active military personnel than for civilians. The combination of increased physical demands and a protracted time to treatment highlights the need for better recognition of FAI in military members. Future studies are necessary to determine whether earlier intervention may prevent or delay the progression to end-stage OA and the need for total hip arthroplasty.
文摘Objective. To introduce a new spinal internal fixation system, Texas Scottish Rite Hospital (TSRH), and to investigate its early clinical outcomes.Methods. The preliminary clinical outcomes of 15 patients with thoracolumbar or lumbar scoliosis treated by anterior spinal fusion with TSRH instrumentation were studied retrospectively. Fourteen patients were diagnosed as idiopathic scoliosis and 1 as neuromuscular scoliosis.Results. Preoperatively, the Cobb's angle on the coronal plane was 55. 8° (range 35° - 78°), and 14° postoperatively, with an average correction of 74. 8 %. The average unfused thoracical curve was 35. 9 ° preoperatively (range 26° - 51°) and 21. 8° (10°-42° ) postoperatively, with 40% correction. The sagittal curve of lumbar was kept physiologically, preoperative 27. 9° and postoperative 25. 7° respectively. The trunk shift was 13.4 mm (5 - 28mm) preoperatively and 3. 5 mm (0-7 mm) postoperatively. The averaged apic vertebra derivation was 47. 8 mm (21 - 69 mm) before operation and 10. 8 mm (3-20 mm) after operation. The distance of C7 to center sacrum vertical line (CSVL) was 19. 5 mm(16 - 42)preoperatively and 11. 3 mm (0-32 mm) postoperatively. The apical vertebra rotation was 3 degree in 15 patients preoperatively, and were improved to normal in 10 patients, 1 degree in 4 patients, and 2 degree in 1 patients postoperatively. None had neurological injury and infection. Only 1 patient complained a cool feeling in the low extremity of concave side, and the symptom vanished at 3-month followed up.Conclusion. If used appropriately, TSRH anterior spinal system is a good treatment for low thoracic or thoracic lumbar scoliosis.
文摘Objective:To introduce a key-vertebral-screws technique(KVST) in the surgical treatment of scoliosis extending to main thoracic levels, and to find the role of fulcrum bending in predicting the result of surgical treatment for scoliosis by this technique. Methods: Seventeen consecutive patients with scoliosis extending to main thoracic spine,who underwent pure posterior fusion without anterior or posterior release by KVST between January 2004 and July 2005 were evaluated for fulcrum bending flexibility, surgical correction rate, fulcrum bending correction index (FBCI) in main thoracic curves. Universal Spine System (USS) instrumentation was used in 15 cases,Monarch in another 2 cases. The severity of the curves was measured by Cobb's method using Rad Work 6. 0 software. Preoperative standing AP radiographs, preoperative fulcrum bending anterioposterior (AP) radiographs, postoperative standing AP radiographs, and most recent follow-up standing AP radiographs for spine were measured and recorded. All the data were analyzed with two-sample paired t-test by Origin 7. 0 software. Results: Infection and neurological complications were not noted. No major complications were found. Just one case had some axial back pain, which got a full recovery from physiotherapy for 2 weeks. In the X-ray, there was an average correction of 71. 5% of the fused main thoracic curves, which had no significant lose of correction in final follow-up. For the whole fused main thoracic curves, the fulcrum bending flexibility were lower to operation correction rate (P = 0. 013). The average FBCI was 123%. From the data, the more rigid curves (especially fulcrum bending flexibility <50%), the more correction rate operation could get, compared with fulcrum bending flexibility. Conclusion: (1) KVST is a good method in the surgical treatment of thoracic scoliosis, which can get satisfying result with lower medical cost. (2) Fulcrum bending flexibility is lower than operative correction rate by KVST in main thoracic curves (P<0. 05). In the more rigid curves assessed by fulcrum-bending radiograph, the operative corrective could be gained, especially in the curves which FBCI is lower than 50%.
文摘Objective: To identify eukaryotic expression vector of human bone morphogenetic protein 2 pcDNA3/BMP2, verify its expression in transfected human mesenchymal stem cells (hMSCs) and the effect on hMSCs differentiation. Methods: The BMP2 gene was cloned into a eukaryotic expression vector pcDNA3. Transfected the recombinant into hMSCs by liposome. Immunnohistochemistry and in situ hybridization methods were used to identify the expression of BMP2 mRNA and protein; ALP and Von Kossa stains were performed to identify the BMP2 gene differentiated effect on the hMSCs. Results: The pcDNA3/BMP2 fragments were as large as theory. BMP2 mRNA and protein were expressed and synthesized both in 48 h and 4 weeks after transfection, the ALP and Ca deposit exhibition, which marked the osteogenic lineage of hMSCs, were enhanced and sped. Conclusion: Transfection of pcDNA3/BMP2 is able to provide transient and persistent expression in hMSCs, and promote the MSCs differentiation to osteogenic lineage.
