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Cellular senescence-driven transcriptional reprogramming of the MAFB/NOTCH3 axis activates the PI3K/AKT pathway and promotes osteosarcoma progression

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Genes & Diseases 2024年第2期11卷 952-963页

作者： Zhenhao Zhang Doudou Jing Baijun Xuan Zhicai Zhang Wei Wu Zengwu Shao department of orthopedics Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430022China department of orthopedics The Second Hospital of Shanxi Medical UniversityTaiyuanShanxi 030001China department of Cardiology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430022China

Osteosarcoma is the most common primary malignancy of bones and primarily occurs in adolescents and young ***,a second smaller peak of osteosarcoma incidence was reported in the elderly aged more than *** patients with osteosarcoma exhibit different characteristics compared to young patients,which usually results in a poor *** mechanism underlying osteosarcoma development in elderly patients is intriguing and of significant value in clinical *** cells can accelerate tumor progression by metabolic *** research has shown that methylmalonic acid(MMA)was significantly up-regulated in the serum of older individuals and played a central role in the development of aggressive *** found that the significant accumulation of MMA in elderly patients imparted proliferative potential to osteosarcoma *** expression of MAFB was excessively up-regulated in osteosarcoma specimens and was further enhanced in response to MMA accumulation as the patient ***,we first confirmed a novel molecular mechanism between cellular senescence and cancer,in which the MMA-driven transcriptional reprogramming of the MAFB-NOTCH3 axis accelerated osteosarcoma progression via the activation of PI3K-AKT ***,the down-regulation of the MAFB-NOTCH3 axis increased the sensitivity and effect of AKT inhibitors in osteosarcoma through significant inhibition of AKT *** conclusion,we confirmed that MAFB is a novel age-dependent biomarker for osteosarcoma,and targeting the MAFB-NOTCH3 axis in combination with AKT inhibition can serve as a novel therapeutic strategy for elderly patients with osteosarcoma in experimental and clinical trials.

关键词： Cellular senescence Elderly patients MAFB-NOTCH3axis Methylmalonic acid Osteosarcoma PI3K-AKTpathway

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Irisin-loaded electrospun core-shell nanofibers as calvarial periosteum accelerate vascularized bone regeneration by activating the mitochondrial SIRT3 pathway

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Regenerative Biomaterials 2024年第1期3卷 44-57页

作者： Xi Hua Mingzhuang Hou Lei Deng Nanning Lv Yong Xu Xuesong Zhu Huilin Yang Qin Shi Hao Liu Fan He department of Orthopaedics The First Affiliated Hospital of Soochow UniversitySoochow UniversitySuzhou 215006China Orthopaedic Institute Suzhou Medical CollegeSoochow UniversitySuzhou 215000China department of orthopedics Suzhou Wuzhong People’s HospitalSuzhouJiangsu Province 215128China department of Orthopedic surgery Lianyungang Clinical College of Xuzhou Medical UniversityLianyungang 222003China

The scarcity of native periosteum poses a significant clinical barrier in the repair of critical-sized bone *** challenge of enhancing regenerative potential in bone healing is further compounded by oxidative stress at the fracture ***,the introduction of artificial periosteum has demonstrated its ability to promote bone regeneration through the provision of appropriate mechanical support and controlled release of proosteogenic *** this study,a poly(L-lactic acid)(PLLA)/hyaluronic acid(HA)-based nanofibrous membrane was fabricated using the coaxial electrospinning *** incorporation of irisin into the core-shell structure of PLLA/HA nanofibers(PLLA/HA@Irisin)achieved its sustained *** vitro experiments demonstrated that the PLLA/HA@Irisin membranes exhibited favorable *** osteogenic differentiation of bone marrow mesenchymal stem cells(BMMSCs)was improved by PLLA/HA@Irisin,as evidenced by a significant increase in alkaline phosphatase activity and matrix ***,PLLA/HA@Irisin significantly enhanced the mitochondrial function of BMMSCs via the activation of the sirtuin 3 antioxidant *** assess the therapeutic effectiveness,PLLA/HA@Irisin membranes were implanted in situ into critical-sized calvarial defects in *** results at 4 and 8 weeks post-surgery indicated that the implantation of PLLA/HA@Irisin exhibited superior efficacy in promoting vascularized bone formation,as demonstrated by the enhancement of bone matrix synthesis and the development of new blood *** results of our study indicate that the electrospun PLLA/HA@Irisin nanofibers possess characteristics of a biomimetic periosteum,showing potential for effectively treating critical-sized bone defects by improving the mitochondrial function and maintaining redox homeostasis of BMMSCs.

关键词： periosteum irisin mitochondrial function critical-sized bone defect redox homeostasis

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Effect of tubastatin A on NLRP3 inflammasome activation in macrophages under hypoxia/ reoxygenation conditions

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World Journal of Emergency Medicine 2024年第4期15卷 289-296页

作者： Hao Li Chang Liu Ying Cui Panpan Chang Wei Chong department of Emergency Medicine the First Hospital of China Medical UniversityShenyang 110001China trauma Medicine Center Peking University People's HospitalBeijing 100871China Key Laboratory of trauma and Neural Regeneration Peking UniversityBeijing 100871China National Center for trauma Medicine of China Beijing 100871China

BACKGROUND:There are currently no effective drugs to mitigate the ischemia/reperfusion injury caused by fluid resuscitation after hemorrhagic shock(HS).The aim of this study was to explore the potential of the histone deacetylase 6(HDAC6)-specific inhibitor tubastatin A(TubA)to suppress nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)inflammasome activation in macrophages under hypoxia/reoxygenation(H/R)***:The viability of RAW264.7 cells subjected to H/R after treatment with different concentrations of TubA was assessed using a cell-counting kit-8(CCK8)***,2.5μmol/L TubA was used with RAW264.7 cells under H/R ***264.7 cells were divided into three groups,namely the control,H/R,and TubA *** levels of reactive oxygen species(ROS)in the cells were detected using fluorescence *** protein expression of HDAC6,heat shock protein 90(Hsp90),inducible nitric oxide synthase(iNOS),NLRP3,gasdermin-D(GSDMD),Caspase-1,GSDMD-N,and Caspase-1 p20 was detected by western *** levels of interleukin-1β(IL-1β)and IL-18 in the supernatants were detected using enzyme-linked immunosorbent assay(ELISA).RESULTS:HDAC6,Hsp90,and iNOS expression levels were significantly higher(P<0.01)in the H/R group than in the control group,but lower in the TubA group than in the H/R group(P<0.05).When comparing the H/R group to the control group,ROS levels were significantly higher(P<0.01),but significantly reduced in the TubA group(P<0.05).The H/R group had higher NLRP3,GSDMD,Caspase-1,GSDMD-N,and Caspase-1 p20 expression levels than the control group(P<0.05),however,the TubA group had significantly lower expression levels than the H/R group(P<0.05).IL-1βand IL-18 levels in the supernatants were significantly higher in the H/R group compared to the control group(P<0.01),but significantly lower in the TubA group compared to the H/R group(P<0.01).CONCLUSION:TubA inhibited the expression of HDAC6,Hsp90,and iNOS in macrophages

关键词： Hemorrhagic shock Hypoxia/reoxygenation Macrophage NLRP3 Tubastatin A

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Indocyanine green:The guide to safer and more effective surgery

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World Journal of Gastrointestinal surgery 2024年第3期16卷 641-649页

作者： Pietro Fransvea Maria Michela Chiarello Valeria Fico Maria Cariati Giuseppe Brisinda Emergency surgery and trauma Center Fondazione Policlinico Universitario Agostino Gemelli IRCCSRome 00168Italy department of surgery Azienda Sanitaria Provinciale di CosenzaCosenza 87100Italy department of surgery Azienda Sanitaria Provinciale di CrotoneCrotone 88900Italy department of Abdominal and Endocrine Metabolic Medical and Surgical Sciences Fondazione Policlinico Universitario A Gemelli IRCCSRome 00168Italy

In this editorial we comment on the article by Kalayarasan and co-workers published in the recent issue of the World Journal of Gastrointestinal *** authors present an interesting review on the use of indocyanine green fluo-rescence in different aspects of abdominal *** also highlight future perspectives of the use of indocyanine green in mini-invasive ***-cyanine green,used for fluorescence imaging,has been approved by the Food and Drug Administration and is safe for use in *** can be administered in-travenously or *** its advent,there have been several advance-ments in the applications of indocyanine green,especially in the surgical field,such as intraoperative mapping and biopsy of sentinel lymph node,measurement of hepatic function prior to resection,in neurosurgical cases to detect vascular anomalies,in cardiovascular cases for patency and assessment of vascular ab-normalities,in predicting healing following amputations,in helping visualization of hepatobiliary anatomy and blood vessels,in reconstructive surgery,to assess flap viability and for the evaluation of tissue perfusion following major trauma and *** these reasons,the intraoperative use of indocyanine green has become common in a variety of surgical specialties and transplant ***-lorectal surgery has just lately begun to adopt this technique,particularly for perfusion visualization to prevent anastomotic *** regular use of in-docyanine green coupled with fluorescence angiography has recently been pro-posed as a feasible tool to help improve patient *** the best available data,it has been shown that routine use of indocyanine green in colorectal surgery reduces the rates of anastomotic *** use of indocyanine green is proven to be safe,feasible,and effective in both elective and emergency ***,additional robust evidence from larger-scale,high-quality studies is essential before incorporating indocyanine g

关键词： Indocyanine green Colorectal surgery Fluorescence-guided surgery Gastrointestinal surgery Hepato-biliary surgery Pancreatic surgery Surgical oncology

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SPOCK2， a novel potential target for cereal intake in knee osteoarthritis

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Food Science and Human Wellness 2024年

作者： Erliang Li Jin Sun Haishi Zheng Jiachen Wang Peng Xu department of orthopedics， The First Affiliated Hospital of Xi'an Jiaotong University department of Joint surgery， Honghui Hospital， Xi'an Jiaotong University department of Orthopaedics， The Tangdu Hospital of Air Force Military Medical University

Lifestyle is related to many chronic diseases， such as knee osteoarthritis （KOA）. Food intake is important because it can be controlled. However， the causal relationship of food intake and KOA still remain unclear. To identify the relationship between food intake and KOA and to screen relevant targets. First， we performed two-sample Mendelian randomization （MR） analysis. A total of 16 kinds of food intake datasets were included， the inverse variance-weighted analysis showed that the KOA was negatively correlated with cereal intake (odds ratio[OR]0.48; 95% CI 0.35-0.68; P = 1.98 × 10-5). Second， potential drug targets of KOA in plasma were explored， SPOCK2 as the causal protein for plasma with KOA， and increased SPOCK2 (OR 0.84; 95% CI 0.77 – 0.92; P = 5.52 × 10- 5)， decreased the risk of KOA. Integrated transcriptomic analysis （P = 0.0285） and in vivo （P = 0.0395） showed consistent results. Finally， by metabolomics analysis and molecular docking， seven co-expressed small molecules were detected in cereal and were bound to SPOCK2. Our findings indicate the cereal intake was negatively correlated with KOA， and support the SPOCK2 as a novel potential target for cereal intake in KOA. Our study will provide clinical dietary guidance for KOA patients and provide a theoretical basis for the development of novel， side-effect-free drugs for KOA.

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Millimeter waves in medical applications:status and prospects

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Intelligent Medicine 2024年第1期4卷 16-21页

作者： Honglin Wang Lin Lu Pengran Liu Jiayao Zhang Songxiang Liu Yi Xie Tongtong Huo Hong Zhou Mingdi Xue Ying Fang Jiaming Yang Zhewei Ye department of orthopedics surgery Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430022China departments of orthopedics Renmin Hospital of Wuhan UniversityWuhanHubei 430060China

Millimeter waves are electromagnetic waves with wavelengths of 1–10 mm,which have characteristics of high frequency and short *** have gradually and widely been used in engineering and medical *** have identified studies related to millimeter waves in the biomedical field and summarized the biological effects of millimeter waves and their current status in medical ***,the shortcomings of existing studies and future developments were analyzed and discussed,with the aim of providing a reference for further research and development of millimeter waves in the medical field.

关键词： Millimeter wave Biological effects Medical applications Vital signs monitoring

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Treatment of a femoral neck fracture combined with ipsilateral femoral head and intertrochanteric fractures: A case report

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World Journal of orthopedics 2024年第10期15卷 973-980页

作者： Xiang Yu Yu-Zhi Li Hai-Jian Lu Bing-Li Liu department of orthopedics Shanghai Seventh People's HospitalShanghai 200000China

BACKGROUND This article presents a rare case of a complex hip fracture involving the ipsilateral femoral neck,trochanter,and femoral head,that was accompanied by hip ***,there is no established standard treatment method for this specific type of ***,it is crucial to comprehensively consider factors such as patient age,fracture type,and degree of displacement to achieve a successful *** SUMMARY A 38-year-old man sustained a comminuted fracture of his right hip as a result of a car *** injuries included a fracture of the femoral head,a fracture of the femoral neck,an intertrochanteric fracture of the femur,and a posterior dislocation of the hip on the same *** opted for a treatment approach combining the use of a proximal femoral locking plate,cannulated screws,and Kirschner *** the surgery,we developed an individualized rehabil-itation program to restore patient limb *** For this complex fracture,we selected appropriate internal fixation and for-mulated individualized rehabilitation,which ultimately achieved good results.

关键词： Locking plate Femoral neck fracture Femoral head fracture Intertrochanteric fracture Open reduction and internal fixation Case report

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Scutellarein Ameliorated Chondrocyte Inflammation and Osteoarthritis in Rats

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Current Medical Science 2024年第2期44卷 355-368页

作者： Shao-ze JING Shu-han YANG Yun-kun QU Hai-hu HAO Hua WU department of orthopedics Third Hospital of Shanxi Medical UniversityShanxi Bethune HospitalShanxi Academy of Medical SciencesTongji Shanxi HospitalTaiyuan 030032China department of orthopedics Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

Objective:Osteoarthritis(OA)is a degenerative joint disorder characterized by the gradual degradation of joint cartilage and local *** study aimed to investigate the anti-OA effect of scutellarein(SCU),a single-unit flavonoid compound obtained from Scutellaria barbata ***,in ***:The extracted rat chondrocytes were treated with SCU and IL-1β.The chondrocytes were divided into control group,IL-1βgroup,IL-1β+SCU 50µmol/L group,and IL-1β+SCU 100µmol/L *** of rat chondrocytes was observed by toluidine blue and safranin O ***-8 method was used to detect the cytotoxicity of ***,qRT-PCR,Western blotting,immunofluorescence,SAβ-gal staining,flow cytometry,and bioinformatics analysis were applied to evaluate the effect of SCU on rat chondrocytes under IL-1β***,anterior cruciate ligament transection(ACL-T)was used to establish a rat OA *** changes were detected by safranin O/fast green,hematoxylin-eosin(HE)staining,and ***:SCU protected cartilage and exhibited anti-inflammatory effects via multiple ***,it could enhance the synthesis of extracellular matrix in cartilage cells and inhibit its *** addition,SCU partially inhibited the nuclear factor kappa-B/mitogen-activated protein kinase(NF-κB/MAPK)pathway,thereby reducing inflammatory cytokine production in the joint ***,SCU significantly reduced IL-1β-induced apoptosis and senescence in rat chondrocytes,further highlighting its potential role in OA *** vivo experiments revealed that SCU(at a dose of 50 mg/kg)administered for 2 months could significantly delay the progression of cartilage damage,which was reflected in a lower Osteoarthritis Research Society International(OARSI)score,and reduced expression of matrix metalloproteinase 13(MMP13)in ***:SCU is effective in the therapeutic management of OA and could serve as a potential candidate f

关键词： scutellarein osteoarthritis apoptosis mitogen-activated protein kinase(MAPK) nuclear factor kappa-B(NF-κB)

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Bone-targeting engineered small extracellular vesicles carrying anti-miR-6359-CGGGAGC prevent valproic acid-induced bone loss

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Signal Transduction and Targeted Therapy 2024年第2期9卷 751-765页

作者： Xudong Xie Peng Cheng Liangcong Hu Wu Zhou Detai Zhang Samuel Knoedler Guodong Liu Yuan Xiong Hang Xue Yiqiang Hu Barbara Kern Doha Obed Adriana CPanayi Lang Chen Chenchen Yan Ze Lin Guandong Dai Bobin Mi Yingze Zhang Guohui Liu department of orthopedics Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration Wuhan 430022China department of Clinical Laboratory Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430022P.R.China Division of Plastic surgery Brigham and Women’s HospitalHarvard Medical SchoolBostonMA 02152USA department of Plastic surgery and Hand surgery Klinikum Rechts der IsarTechnical University of MunichMunichGermany Medical Center of trauma and War Injuries Daping HospitalArmy Medical UniversityChonqing 400042China department of Plastic surgery Campus CharitéMitte|Campus Virchow-KlinikumCharité-Universitätsmedizin Berlincorporate member of Freie Universität BerlinHumboldt-Universität zu Berlin and Berlin Institute of HealthBerlinGermany Berlin Institute of Health Charité-Universitätsmedizin BerlinBerlinGermany department of Plastic AestheticHand and Reconstructive SurgeryHannover Medical SchoolHannoverGermany department of Hand Plastic and Reconstructive SurgeryMicrosurgeryBurn CenterBG Trauma Center LudwigshafenUniversity of HeidelbergLudwig-Guttmann-Strasse 1367071 Ludwigshafen/RhineGermany Pingshan District People’s Hospital of Shenzhen Pingshan General Hospital of Southern Medical UniversityShenzhenGuangdong 518118China department of Orthopaedic surgery The Third Hospital of Hebei Medical UniversityNO.139 Ziqiang RoadShijiazhuang 050051China

The clinical role and underlying mechanisms of valproic acid(VPA)on bone homeostasis remain ***,we confirmed that VPA treatment was associated with decreased bone mass and bone mineral density(BMD)in both patients and *** effect was attributed to VPA-induced elevation in osteoclast formation and *** RNA-sequencing,we observed a significant rise in precursor miR-6359 expression in VPA-treated osteoclast precursors in vitro,and further,a marked upregulation of mature miR-6359(miR-6359)in vivo was demonstrated using quantitative real-time PCR(qRT-PCR)and miR-6359 fluorescent in situ hybridization(miR-6359-FISH).Specifically,the miR-6359 was predominantly increased in osteoclast precursors and macrophages but not in neutrophils,T lymphocytes,monocytes and bone marrow-derived mesenchymal stem cells(BMSCs)following VPA stimulation,which influenced osteoclast differentiation and bone-resorptive ***,VPA-induced miR-6359 enrichment in osteoclast precursors enhanced reactive oxygen species(ROS)production by silencing the SIRT3 protein expression,followed by activation of the MAPK signaling pathway,which enhanced osteoclast formation and activity,thereby accelerating bone ***,there are no medications that can effectively treat VPA-induced bone ***,we constructed engineered small extracellular vesicles(E-sEVs)targeting osteoclast precursors in bone and naturally carrying anti-miR-6359 by introducing of EXOmotif(CGGGAGC)in the 3’-end of the anti-miR-6359 *** confirmed that the E-sEVs exhibited decent bone/osteoclast precursor targeting and exerted protective therapeutic effects on VPA-induced bone loss,but not on ovariectomy(OVX)and glucocorticoid-induced osteoporotic models,deepening our understanding of the underlying mechanism and treatment strategies for VPA-induced bone loss.

关键词： miR protective stimulation

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Impact of computed tomography/magnetic resonance imaging registration on rehabilitation after percutaneous endoscopic decompression for lumbar stenosis: Retrospective study

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World Journal of orthopedics 2024年第10期15卷 939-949页

作者： Xiao-Bo Guo Jin-Wei Chen Jun-Yang Liu Jiang-Tao Jin department of orthopedics Jincheng General HospitalJincheng 048006Shanxi ProvinceChina

BACKGROUND Percutaneous endoscopic lumbar decompression(PELD)shows promise for lumbar spinal stenosis(LSS)treatment,but its use is limited by the disease's complexity and procedural *** In this study,the effects of preoperative planning and intraoperative guidance with computed tomography(CT)/magnetic resonance imaging(MRI)registration techniques on PELD for LSS and postoperative rehabilitation outcomes were *** This retrospective study was conducted with data from patients who underwent PELD for LSS between January 2021 and December *** were assigned to preoperative CT/MRI registration and control *** collected included the operative time,length of hospital stay,visual analog scale(VAS)scores for low back and leg pain,and the Japanese Orthopaedic Association(JOA)lumbar spine *** between groups were assessed using Student’s t *** Data from 135 patients(71 in the CT/MRI registration group,64 in the control group)were *** operative time was significantly shorter in the CT/MRI registration group(P=0.007).At 2 months postoperatively,both groups showed significant reductions in VAS leg and low back pain scores(all P<0.001)and improvements in the JOA score(both P<0.001).No complication or death ***,pain and JOA scores were similar between groups(P=0.830,P=0.470,and P=0.287,respectively).At 2 months postoperatively,patients in the CT/MRI registration group reported lower leg and low back pain levels(P<0.001 and P=0.001,respectively)and had higher JOA scores(P=0.004)than did patients in the control *** Preoperative CT/MRI registration for PELD for LSS reduced the operative time and VAS pain scores at 2 months and improved JOA scores,demonstrating enhanced effectiveness and safety.

关键词： Endoscopy Spinal stenosis Lumbar vertebrae Tomography X-Ray computed Magnetic resonance imaging

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