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Liposomalα-cyperone targeting bone resorption surfaces suppresses osteoclast differentiation and osteoporosis progression via the PI3K/Akt axis

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Nano Research 2024年第4期17卷 2949-2959页

作者： Lin Yang Xueying An Wang Gong Wenshu Wu Bin Liu Xiaoyan Shao Yansi Xian Rui Peng Baosheng Guo Qing Jiang Division of sports Medicine and Adult Reconstructive surgery Department of Orthopedic SurgeryNanjing Drum Tower Hospital Clinical College of Nanjing Medical University321 Zhongshan RoadNanjing 210008China Branch of National Clinical Research Center for Orthopedics Sports Medicine and RehabilitationNanjing 210008China State Key Laboratory of Pharmaceutical Biotechnology Medical SchoolNanjing University&Division of Sports Medicine and Adult Reconstructive SurgeryDepartment of Orthopedic SurgeryNanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical SchoolNanjing 210008China

Osteoporosis is a metabolic dysregulation of bone that occurs mainly in postmenopausal women,and the hyperfunction of osteoclasts is the primary contributor to postmenopausal ***,the development of effective therapeutic drugs and precise delivery systems remains a challenge in the field of anti-absorption ***,we reported theα-cyperone(α-CYP)for anti-osteoporosis and developed a liposome-based nano-drug delivery system ofα-CYP,that specifically targets the bone resorption ***,we found that theα-CYP,one of the major sesquiterpenes of Cyperus rotundus L.,attenuated the progression of osteoporosis in ovariectomized(OVX)mice and down-regulated the expression of phosphorylated proteins of phosphoinositide 3-kinase(PI3K)and protein kinase B(Akt),causing down-regulation of osteoclast-related genes/proteins and curbing osteoclast ***,α-CYP reversed the activation of osteoclastic differentiation and enhanced osteoporosis-related proteins expression caused by PI3K/Akt agonist(YS-49).More importantly,we adopted the osteoclastic resorption surface targeting peptide Asp8 and constructed the liposome(lipαC@Asp8)to deliverα-CYP to osteoclasts and confirmed its anti-osteoporosis effect and enhanced osteoclast inhibition by blocking PI3K/Akt *** conclusion,this study demonstrated thatα-CYP inhibits osteoclast differentiation and osteoporosis development by silencing PI3K/Akt pathway,and the liposome targeting delivery systems loaded withα-CYP might provide a novel and effective strategy to treat osteoporosis.

关键词： osteoporosis α-cyperone osteoclast phosphoinositide 3-kinase/protein kinase B(PI3K/Akt) liposome

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Paternal mixed exposure to nicotine/ethanol/caffeine damaged cartilage quality in paternal/offspring rats and its differential glucocorticoid regulation mechanisms

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Food Science and Human Wellness 2024年

作者： Yi Liu Hao Xiao Yi Liu Bin Li Hui Wang Liaobin Chen Division of joint surgery and sports Medicine Department of Orthopedic surgery Zhongnan Hospital of Wuhan University Hubei Provincial Key Laboratory of Developmentally Originated Disease joint Disease Research Center of Wuhan University Department of Pharmacology Wuhan University School of Basic Medical Sciences

Nicotine， ethanol， and caffeine are the most common exogenous substances in the men’s living environment， but their effects on the cartilage quality in the father and offspring have not been reported. According to the average daily intake of adult men， we constructed a male rat model of paternal mixed exposure (PME) to low-dose nicotine (0.1 mg/kg.d)， ethanol (0.5 g/kg.d)， and caffeine (7.5 mg/kg.d) for 8 weeks. Then， the male rats mated with normal female rats to obtain offspring. The results showed that PME reduced the cartilage quality of paternal and offspring rats. Among them， the paternal cartilage was damaged by enhancing matrix degradation， while the offspring cartilage was damaged by reducing matrix synthesis. The cartilage damage in male offspring rats was more evident than in female offspring. It was further confirmed that differential GC regulation mechanisms were the main reasons for the intergenerational differential damage of paternal/offspring cartilage quality caused by PME. In addition， the sex hormone receptor AR and ERβ mediated the sex difference of PME-induced fetal cartilage dysplasia by affecting the binding degree of GR/P300. This study provided a theoretical and experimental basis for guiding male healthy lifestyle and exploring early prevention and treatment strategies for paternal diseases.

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Activation of the PGC-1α-mediated mitochondrial glutamine metabolism pathway attenuates female offspring osteoarthritis induced by prenatal excessive prednisone

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Science China Life Sciences 2024年

作者： Qingxian Li Fan Zhang Yongguo Dai Liang Liu Liaobin Chen Hui Wang Department of Orthopedic surgery Zhongnan Hospital of Wuhan University Department of Pharmacology School of Basic Medical Sciences Wuhan University joint Disease Research Center of Wuhan University Division of Joint Surgery and Sports Medicine Hubei Provincial Key Laboratory of Developmentally Originated Disease

Osteoarthritis is a chronic, age-related joint disease. Previous studies have shown that osteoarthritis develops during intrauterine development. Prednisone is frequently used to treat pregnancies complicated by autoimmune diseases. However, limited research has been conducted on the enduring effects of prednisone use during pregnancy on the offspring. In this study, we investigated the effect of excessive prednisone exposure on cartilage development and susceptibility to osteoarthritis in the offspring. We found that prenatal prednisone exposure(PPE) impaired cartilage extracellular matrix(ECM) synthesis, resulting in poor cartilage pathology in female offspring during the adult period, which was further exacerbated after long-distance running stimulation. Additionally, PPE suppressed cartilage development during the intrauterine period. Tracing back to the intrauterine period, we found that Pred, rather than prednisone, decreased glutamine metabolic flux, which resulted in increased oxidative stress, and decreased histone acetylation, and expression of cartilage phenotypic genes. Further, PGC-1α-mediated mitochondrial biogenesis, while PPE caused hypermethylation in the promoter region of PGC-1α and decreased its expression in fetal cartilage by activating the glucocorticoid receptor, resulting in a reduction of glutamine flux controlled by mitochondrial biogenesis. Additionally, overexpression of PGC-1α(either pharmacological or through lentiviral transfection) reversed PPEand Pred-induced cartilage ECM synthesis impairment. In summary, this study demonstrated that PPE causes chondrodysplasia in female offspring and increases their susceptibility to postnatal osteoarthritis. Hence, targeting PGC-1α early on could be a potential intervention strategy for PPE-induced osteoarthritis susceptibility.

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Bipolar hip arthroplasty using conjoined tendon preserving posterior lateral approach in treatment of displaced femoral neck fractures

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World Journal of Clinical Cases 2024年第6期12卷 1076-1083页

作者： Ting-Xin Yan Sheng-Jie Dong Bo Ning Yu-Chi Zhao Department of joint surgery Yantaishan HospitalYantai 264003Shandong ProvinceChina Department of joint surgery Dongying People's HospitalDongying 257091Shandong ProvinceChina

BACKGROUND Hip fractures account for 23.8%of all fractures in patients over the age of 75 *** than half of these patients are older than 80 *** hemiarthroplasty(BHA)was established as an effective management option for these *** approaches can be used for the BHA ***,there is a high risk of postoperative *** conjoined tendon-preserving posterior(CPP)lateral approach was introduced to reduce postoperative dislocation *** To evaluate the effectiveness and safety of the CPP lateral approach for BHA in elderly *** We retrospectively analyzed medical data from 80 patients with displaced femoral neck fractures who underwent *** patients were followed up for at least 1 *** the 80 patients,57(71.3%)were *** time to operation averaged 2.3 d(range:1-5 d).The mean age was 80.5 years(range:67-90 years),and the mean body mass index was 24.9 kg/m^(2)(range:17-36 kg/m^(2)).According to the Garden classification,42.5%of patients were typeⅢand 57.5%of patients were typeⅣ.Uncemented bipolar hip prostheses were used for all *** conjoined tendons,dislocations,and adverse complications during and after surgery were *** The mean postoperative follow-up time was 15.3 months(range:12-18 months).The average surgery time was 52 min(range:40-70 min)with an average blood loss of 120 mL(range:80-320 mL).The transfusion rate was 10%(8 of 80 patients).The gemellus inferior was torn in 4 patients(5%),while it was difficult to identify in 2 patients(2.5%)during *** posterior capsule was punctured by the fractured femoral neck in 3 patients,but the conjoined tendon and the piriformis tendon remained *** patients had stem varus greater than 3 degrees or femoral *** were no patients with stem subsidence more than 5 mm at the last *** postoperative dislocations were observed throughout the follow-up *** significance was found between preoperative an

关键词： Conjoined tendon preserving Bipolar hip arthroplasty Femoral neck fractures Postoperative dislocation Posterolateral approach

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Skeletal interoception in osteoarthritis

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Bone Research 2024年第2期12卷 241-254页

作者： Dinglong Yang Jiawen Xu Ke Xu Peng Xu Department of joint surgery Honghui HospitalXi’an Jiaotong UniversityXi’an 710054China Department of Orthopedic surgery and Orthopedic Research Institute West China HospitalSichuan UniversityChengdu 610041China

The interoception maintains proper physiological conditions and metabolic homeostasis by releasing regulatory signals after perceving changes in the internal state of the *** its various forms,skeletal interoception specifically regulates the metabolic homeostasis of ***(OA)is a complex joint disorder involving cartilage,subchondral bone,and *** subchondral bone undergoes continuous remodeling to adapt to dynamic joint *** findings highlight that skeletal interoception mediated by aberrant mechanical loads contributes to pathological remodeling of the subchondral bone,resulting in subchondral bone sclerosis in *** skeletal interoception is also a potential mechanism for chronic synovial inflammation in *** this review,we offer a general overview of interoception,specifically skeletal interoception,subchondral bone microenviroment and the aberrant subchondral *** also discuss the role of skeletal interoception in abnormal subchondral bone remodeling and synovial inflammation in OA,as well as the potential prospects and challenges in exploring novel OA therapies that target skeletal interoception.

关键词： homeostasis inflammation releasing

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The deterministic condition for the ground reaction force acting point on the combined knee valgus and tibial internal rotation moments in early phase of cutting maneuvers in female athletes

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Journal of Sport and Health Science 2024年第3期13卷 376-386页

作者： Issei Ogasawara Ken Ohta Gajanan S.Revankar Shoji Konda Yohei Shimokochi Hideyuki Koga Ken Nakata Department of Health and Sport Sciences Graduate School of MedicineOsaka UniversityToyonaka 560-0043Japan sports Sensing Co. LTD.Fukuoka 815-0035Japan Department of Neurology Graduate School of MedicineOsaka UniversitySuita 565-0871Japan Department of Health and Sport Management Osaka University of Health and Sport SciencesSennan-gun 590-0496Japan Department of joint surgery and sports Medicine Graduate School of Medical and Dental SciencesTokyo Medical and Dental UniversityBunkyo-ku 113-8519Japan

Background:Combined knee valgus and tibial internal rotation(VL+IR)moments have been shown to stress the anterior cruciate ligament(ACL)in several in vitro cadaveric *** utilize this knowledge for non-contact ACL injury prevention in sports,it is necessary to elucidate how the ground reaction force(GRF)acting point(center of pressure(CoP))in the stance foot produces combined knee VL+IR moments in risky maneuvers,such as ***,the effects of the GRF acting point on the development of the combined knee VL+IR moment in cutting are still ***:We first established the deterministic mechanical condition that the CoP position relative to the tibial rotational axis differentiates the GRF vector’s directional probability for developing the combined knee VL+IR moment,and theoretically predicted that when the CoP is posterior to the tibial rotational axis,the GRF vector is more likely to produce the combined knee VL+IR moment than when the CoP is anterior to the tibial rotational ***,we tested a stochastic aspect of our theory in a lab-controlled in vivo *** females performed 60˚cutting under forefoot/rearfoot strike conditions(10 trials each).The positions of lower limb markers and GRF data were measured,and the knee moment due to GRF vector was *** trials were divided into anterior-and posterior-CoP groups depending on the CoP position relative to the tibial rotational axis at each 10 ms interval from 0 to 100 ms after foot strike,and the occurrence rate of the combined knee VL+IR moment was compared between trial ***:The posterior-CoP group showed significantly higher occurrence rates of the combined knee VL+IR moment(maximum of 82.8%)at every time point than those of the anterior-CoP trials,as theoretically predicted by the deterministic mechanical ***:The rearfoot strikes inducing the posterior CoP should be avoided to reduce the risk of non-contact ACL injury associated with the com

关键词： Center of pressure Deterministic condition Foot strike pattern Injury mechanism Moment of ground reaction force

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Epidemiology of insertional and midportion Achilles tendinopathy in runners:A prospective cohort study

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Journal of Sport and Health Science 2024年第2期13卷 256-263页

作者： Wenbo Chen Kyra L.A.Cloosterman Sita M.A.Bierma-Zeinstra Marienke van Middelkoop Robert-Jan de Vos Department of Orthopaedic surgery and sports Medicine Erasmus MC University Medical CenterRotterdam 3015GDthe Netherlands Department of General Practice Erasmus MC University Medical CenterRotterdam 3015GDthe Netherlands Department of sports Medicine Huashan HospitalFudan UniversityShanghai 200040China

Background:Achilles tendinopathy(AT)is a common problem among *** is only limited evidence for risk factors for AT,and most studies have not defined the AT *** study has compared the incidence and risk factors between insertional AT and midportion AT,though they are considered *** study aimed to assess incidence and risk factors of AT based on data from a large prospective *** secondary aim was to explore differences in risk factors between insertional and midportion ***:Participants were recruited from among registered runners at registration for running *** were completed at baseline,1 month before the event,1 week before the event,and 1 month after the *** concerning demographics,training load,registered events,and running-related injuries were collected at *** follow-up questionnaires collected information about new injuries.A pain map was used to diagnose midportion and insertional *** primary outcome was the incidence of *** logistic regression analysis was applied to identify risk factors for the ***:We included 3379 participants with a mean follow-up of 20.4 *** incidence of AT was 4.2%.The proportion of insertional AT was 27.7%and of midportion AT was 63.8%;the remaining proportion was a combined type of insertional and midportion *** had a significantly higher incidence(5%,95%confidence interval(95%CI):4.1%-6.0%)than women(2.8%,95%CI:2.0%-3.8%).AT in the past12 months was the most predominant risk factor for new-onset AT(odds ratio(OR)=6.47,95%CI:4.27-9.81).This was similar for both subcategories of AT(insertional:OR=5.45,95%CI:2.51-11.81;midportion:OR=6.96,95%CI:4.24-11.40).Participants registering for an event with a distance of 10/10.55 km were less likely to develop a new-onset AT(OR=0.59,95%CI:0.36-0.97)or midportion AT(OR=0.47,95%CI:0.23-0.93).Higher age had a significant negative association with insertional AT(OR=0.97,95%CI:0.9

关键词： Achilles tendon injury Incidence Risk factor Running-related injury

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Activatable fluorescent probes for imaging and diagnosis of rheumatoid arthritis

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Military Medical Research 2024年第2期11卷 287-307页

作者： Pan Luo Fu-Qiang Gao Wei Sun Jun-You Li Cheng Wang Qing-Yu Zhang Zhi-Zhuo Li Peng Xu Department of joint surgery Honghui HospitalXi'an Jiaotong UniversityXi'an 710054China Department of Orthopedics China-Japan Friendship HospitalBeijing 100029China Department of Orthopaedic surgery of the Perelman School of Medicine University of PennsylvaniaPhiladelphiaPA 19104USA School of Mechanical Engineering Sungkyunkwan UniversitySuwon 16419South Korea Department of Orthopaedic surgery Peking University Third HospitalPeking UniversityBeijing 100191China Department of Orthopedics Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinan 250021China State Key Laboratory of Pharmaceutical Biotechnology Division of Sports Medicine and Adult Reconstructive SurgeryDepartment of Orthopedic SurgeryNanjing Drum Tower Hospitalthe Affiliated Hospital of Nanjing University Medical SchoolNanjing 210008China

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 ***,good prognosis heavily relies on the early diagnosis and effective therapeutic monitoring of *** fluorescent probes play vital roles in the detection and imaging of biomarkers for disease diagnosis and in vivo ***,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.

关键词： Rheumatoid arthritis Fluorescent probe Imaging Diagnosis Biomarker

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Robotic versus laparoscopic surgery for sporadic benign insulinoma:Short-and long-term outcomes

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Hepatobiliary & Pancreatic Diseases International 2024年第4期23卷 399-405页

作者： Zhu-Zeng Yin Yuan-Xing Gao Zhi-Ming Zhao Ming-Gen Hu Wen-Bo Tang Rong Liu Faculty of Hepato-Pancreato-Biliary surgery The First Medical CenterChinese PLA General HospitalBeijing 100853China Institute of Hepatobiliary surgery of Chinese PLA Beijing 100853China Key Laboratory of Digital Hepatobiliary surgery of Chinese PLA Beijing 100853China

Background:Minimally invasive surgery is the optimal treatment for *** present study aimed to compare short-and long-term outcomes of laparoscopic and robotic surgery for sporadic benign ***:A retrospective analysis of patients who underwent laparoscopic or robotic surgery for insulinoma at our center between September 2007 and December 2019 was *** demographic,perioperative and postoperative follow-up results were compared between the laparoscopic and robotic ***:A total of 85 patients were enrolled,including 36 with laparoscopic approach and 49 with robotic *** was the preferred surgical ***-nine patients(69.4%)underwent enucleation;among them,26 and 33 patients underwent laparoscopic and robotic surgery,*** enucleation had a lower conversion rate to laparotomy(0 vs.19.2%,P=0.013),shorter operative time(102.0 vs.145.5 min,P=0.008)and shorter postoperative hospital stay(6.0 vs.8.5 d,P=0.002)than laparoscopic *** were no differences between the groups in terms of intraoperative blood loss,the rates of postoperative pancreatic fistula and *** a median follow-up of 65 months,two patients in the laparoscopic group developed a functional recurrence and none of the patients in the robotic group had a ***:Robotic enucleation can reduce the conversion rate to laparotomy and shorten operative time,which might lead to a reduction in postoperative hospital stay.

关键词： Robotic surgical procedures Laparoscopy Insulinoma Enucleation Pancreatectomy

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Subsequent total joint arthroplasty: Are we learning from the first stage?

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World Journal of Orthopedics 2024年第3期15卷 230-237页

作者： Christine Jiang Wu Colin Penrose Sean Patrick Ryan Michael Paul Bolognesi Thorsten Markus Seyler Samuel Secord Wellman Department of Orthopaedic surgery Duke University HospitalDurhamNC 27710United States Department of Orthopaedic surgery Midwest Center for Joint ReplacementIndianapolisIN 46241United States

BACKGROUND With the increasing incidence of total joint arthroplasty(TJA),there is a desire to reduce peri-operative complications and resource *** degenerative conditions progress in multiple joints,many patients undergo multiple *** To determine if both physicians and patients learn from the patient’s initial arth-roplasty,resulting in improved outcomes following the second *** The institutional database was retrospectively queried for primary total hip arth-roplasty(THA)and total knee arthroplasty(TKA).Patients with only unilateral THA or TKA,and patients undergoing same-day bilateral TJA,were *** demographics,comorbidities,and implant sizes were collected at the time of each procedure and patients were stratified by first vs second *** metrics evaluated included operative time,length of stay(LOS),disposition,90-d readmissions and emergency department(ED)*** A total of 642 patients,including 364 undergoing staged bilateral TKA and 278 undergoing bilateral THA,were *** was no significant difference in demographics or comorbidities between the first and second procedure,which were separated by a mean of 285 *** THA and TKA,LOS was significantly less for the second surgery,with 66%of patients having a shorter hospitalization(Psurgery,patients were significantly more likely to be discharged to home after the second procedure(P=0.033).There was no difference between procedures for post-operative readmissions(P=0.438)or ED visits(P=0.915).CONCLUSION After gaining valuable experience recovering from the initial surgery,a patient’s perioperative outcomes are improved for their second *** may

关键词： Staged total joint arthroplasty Asynchronous total joint arthroplasty Subsequent total joint arthroplasty Contralateral total joint arthroplasty Perioperative outcomes

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