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The evolving roles of Wnt signaling in stem cell proliferation and differentiation, the development of human diseases, and therapeutic opportunities

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Genes & Diseases 2024年第3期11卷 155-187页

作者： Michael Yu kevin Qin Jiaming Fan Guozhi Zhao Piao Zhao Wei Zeng Connie Chen Annie Wang Yonghui Wang jiamin Zhong Yi Zhu William Wagstaff Rex C.Haydon Hue H.Luu Sherwin Ho Michael J.Lee Jason Strelzow Russell R.Reid Tong-Chuan He School of Medicine Rosalind Franklin University of Medicine and ScienceNorth ChicagoIL 60064USA Molecular Oncology Laboratory Department of Orthopedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Ministry of Education Key Laboratory of Diagnostic Medicine and Department of Clinical BiochemistryThe School of Laboratory MedicineChongqing Medical UniversityChongqing 400016China Department of Orthopedic Surgery The First Affliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Urology The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Clinical Laboratory Medicine Shanghai Jiaotong University School of MedicineShanghai 200000China Department of Orthopaedic Surgery Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China Laboratory of Craniofacial Suture Biology and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA Department of Neurology The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguanGuangdong 523475China

The evolutionarily conserved Wnt signaling pathway plays a central role in develop-ment and adult tissue homeostasis across *** proteins are secreted,lipid-modified signaling molecules that activate the canonical(β-catenin dependent)and non-canonical(β-catenin independent)Wnt signaling *** behaviors such as proliferation,differ-entiation,maturation,and proper body-axis specification are carried out by the canonical pathway,which is the best characterized of the known Wnt signaling *** signaling has emerged as an important factor in stem cell biology and is known to affect the self-renewal of stem cells in various *** includes but is not limited to embryonic,hematopoietic,mesenchymal,gut,neural,and epidermal stem *** signaling has also been implicated in tumor cells that exhibit stem cell-like *** signaling is crucial for bone formation and presents a potential target for the development of therapeutics for bone *** surprisingly,aberrant Wnt signaling is also associated with a wide variety of diseases,including *** of Wnt pathway members in cancer can lead to unchecked cell proliferation,epithelial-mesenchymal transition,and ***,advances in the understand-ing of dysregulated Wnt signaling in disease have paved the way for the development of novel therapeutics that target components of the Wnt *** with a brief overview of the mechanisms of canonical and non-canonical Wnt,this review aims to summarize the cur-rent knowledge of Wnt signaling in stem cells,aberrations to the Wnt pathway associated with diseases,and novel therapeutics targeting the Wnt pathway in preclinical and clinical studies.

关键词： β-Catenin Cancer Canonical Wnt Disease Non-canonical Wnt Stem cells Targeted therapy Wnt signaling

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Comparison of Cognitive Registration Transrectal Ultrasound-Guided Targeted Biopsy of Prostate to Systematic 12-Core Biopsy: A Retrospective, Multicentre Study

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Open Journal of Urology 2024年第7期14卷 381-390页

作者： kevin Chang Yue Wei Lee Say Bob Devindran Manoharan Liong Men Long Teoh Sze Yong Teo Rui Ling Chua Zi Wei Department of Urology Hospital Pulau Pinang George Town Malaysia Department of Urology Georgetown Specialist Hospital George Town Malaysia Department of Radiology Hospital Pulau Pinang George Town Malaysia Department of Radiology Georgetown Specialist Hospital George Town Malaysia

Introduction: Prostate cancer (PCa) is the third most prevalent cancer among Malaysian males, often diagnosed at advanced stages, leading to suboptimal outcomes. While transrectal ultrasound-guided systematic biopsy (TRUS-SB) is the primary diagnostic method, prebiopsy multiparametric magnetic resonance imaging (mpMRI) is gaining popularity in identifying suspicious lesions. This study addresses the lack of comprehensive investigations into the efficacy of cognitive registration TRUS targeted biopsy (COG-TB) compared to conventional TRUS-SB, considering the resource limitations of the Malaysian healthcare system. Materials and Methods: A retrospective cohort study was conducted in two Malaysian healthcare facilities. 116 adult patients with a prostate-specific antigen (PSA) level of more than 4 ng/mL who underwent both COG-TB and TRUS-SB between October 2020 and March 2022 were included. Primary outcomes were cancer detection rate and histopathological outcomes, including Gleason score. Results: COG-TB showed a higher overall cancer detection rate (50%) compared to TRUS-SB (44%). Clinically significant cancer detection rates were similar between COG-TB and TRUS-SB (37.1%). Further analysis revealed that both COG-TB and TRUS-SB detected clinically significant cancer in 30.2% of patients, did not detect it in 56.0%, and had conflicting findings in 16 patients (p Conclusion: COG-TB and TRUS-SB have comparable detection rates for clinically significant prostate cancer, with COG-TB showing a higher tendency to detect insignificant prostate cancer. Further studies comparing these methods are warranted.

关键词： Prostate Cancer Multiparametric MRI Targeted Biopsy Cognitive Fusion Transrectal Ultrasound-Guided Biopsy

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The HIF-1α/PLOD2 axis integrates extracellular matrix organization and cell metabolism leading to aberrant musculoskeletal repair

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Bone Research 2024年第2期12卷 289-301页

作者： Heeseog Kang Amy L.Strong Yuxiao Sun Lei Guo Conan Juan Alec C.Bancroft Ji Hae Choi Chase A.Pagani Aysel A.Fernandes Michael Woodard Juhoon Lee Sowmya Ramesh Aaron W.James David Hudson kevin N.Dalby Lin Xu Robert J.Tower Benjamin Levi Center for Organogenesis Regeneration and TraumaDepartment of SurgeryUniversity of Texas SouthwesternDallasTX 75390USA Section of Plastic Surgery Department of SurgeryUniversity of MichiganAnn ArborMI 48109USA Quantitative Biomedical Research Center Peter O’Donnell Jr.School of Public HealthUniversity of Texas SouthwesternDallasTX 75390USA Department of Orthopedics and Sports Medicine University of WashingtonSeattleWA 98195USA Division of Chemical Biology and Medicinal Chemistry College of PharmacyUniversity of Texas at AustinAustinTX 78712USA Department of Pathology Johns Hopkins UniversityBaltimoreMD 21218USA

While hypoxic signaling has been shown to play a role in many cellular processes,its role in metabolism-linked extracellular matrix(ECM)organization and downstream processes of cell fate after musculoskeletal injury remains to be ***(HO)is a debilitating condition where abnormal bone formation occurs within extra-skeletal *** andhypoxia-inducible factor 1α(HIF-1α)activation have been shown to promote ***,the underlying molecular mechanisms bywhich the HIF-1αpathway in mesenchymal progenitor cells(MPCs)contributes to pathologic bone formation remain to ***,we used a proven mouse injury-induced HO model to investigate the role of HIF-1αon aberrant cell ***-cell RNA sequencing(scRNA-seq)and spatial transcriptomics analyses of the HO site,we found that collagen ECM organizationis the most highly up-regulated biological process in *** mesenchymal cell-specific deletion of Hif1α(Hoxa11-CreER^(T2);Hif1a^(fl/fl))significantly mitigated HO in ***-seq analysis of these Hoxa11-CreER^(T2);Hif1a^(fl/fl)mice identified the PLOD2/LOXpathway for collagen cross-linking as downstream of the HIF-1αregulation of ***,our scRNA-seq data and mechanisticstudies further uncovered that glucose metabolism in MPCs is most highly impacted by HIF-1α*** a translational aspect,a pan-LOX inhibitor significantly decreased HO.A newly screened compound revealed that the inhibition of PLOD2 activity in MPCssignificantly decreased osteogenic differentiation and glycolytic *** suggests that the HIF-1α/PLOD2/LOX axis linked tometabolism regulates HO-forming MPC *** results suggest that the HIF-1α/PLOD2/LOX pathway represents a promisingstrategy to mitigate HO formation.

关键词： metabolism skeletal aberrant

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M+博物馆

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世界建筑导报 2024年第3期39卷 96-99页

作者： Virgile Simon Bertrand(摄) kevin Mak(摄) 不详

M+博物馆是西九文化区的一大文化中心,为20世纪和21世纪的艺术、设计、建筑和动态影像的展示场所。仅仅20年前,西九文化区所处之地还是海港的一部分。一块接一块地填海造地,将天然港湾改造成为陆地。现在,这片人工填海的土地是西九文化... 详细信息

M+博物馆是西九文化区的一大文化中心,为20世纪和21世纪的艺术、设计、建筑和动态影像的展示场所。仅仅20年前,西九文化区所处之地还是海港的一部分。一块接一块地填海造地,将天然港湾改造成为陆地。现在,这片人工填海的土地是西九文化区新建筑的建设场地。有意思的是,恰好是另一项曾被视为场地规划的阻碍工程,即机场快线的地下隧道,定义了这片区域的特殊性,成为M+博物馆项目设计的起点。

关键词：文化区场地规划建设场地填海造地动态影像博物馆地下隧道 21世纪

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从BRDF到BPDF:遥感反演基础模型的演进初探

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中国科学：信息科学 2024年第8期54卷 2001-2020页

作者：尚可晏磊张飞舟褚君浩杨彬刘思远 kevin TANSEY 贾秀萍 Oleg DUBOVIK 张子晗李飞北京大学地球与空间科学学院遥感与地理信息系统研究所北京大学空间信息集成与3S工程应用北京市重点实验室北京100871 中国科学院上海技术物理研究所红外物理国家重点实验室上海200083 湖南大学电气与信息工程学院长沙410082 中国兵器工业导航与控制技术研究所北京100089 School of Geography Geologyand the EnvironmentUniversity of LeicesterLeicester LE17RHUK School of Engineering and Technology The University of New South WalesCanberra ACT 2600Australia Laboratoire d'Optique Atmospherique CNRS/UniversitéLilleVilleneuve d'Ascq 59655France

光的本质是横波电磁波矢量,以双向反射分布函数BRDF (bidirectional reflectance distribution function)为基础模型的标量遥感体系只利用植被反射光的整体强度信息,无法进一步区分反射辐射蕴含的叶表、叶内和冠层结构信息;在标量遥感... 详细信息

光的本质是横波电磁波矢量,以双向反射分布函数BRDF (bidirectional reflectance distribution function)为基础模型的标量遥感体系只利用植被反射光的整体强度信息,无法进一步区分反射辐射蕴含的叶表、叶内和冠层结构信息;在标量遥感基础上考虑垂直于电磁波传播方向的二维偏振矢量特性(强度+方向)就能深化为矢量遥感体系,从而有望精确刻画反射光中蕴含的多种信息,提升植被参数反演精度.刻画偏振反射空间分布的双向偏振分布函数BPDF目前存在精度低、泛化性差等问题,因此进一步探索矢量遥感基础理论,构建通用性强的植被矢量遥感基础模型具有迫切的现实需求.本文旨在利用光子与植被元素的相互作用构建通用性较强的植被BPDF物理模型.首先基于光子–植被元素相互作用的光谱不变原理,提出基于方向逃逸概率的植被BPDF物理模型基础形式,并基于植被单次反射的辐射传输理论推导模型解析表达;随后通过考虑叶片散射随干物质含量的变化,提出光谱不变原理优化表达并推导模型通用表达式;最后分别利用三维矢量辐射传输模型和多尺度实测数据实现模型的正演直接验证和间接验证.结果表明,本文构建的BPDF物理模型的解析表达和通用表达在不同植被场景下,对偏振反射率的正演均方根误差可达0.001以内,与矢量辐射传输模型正演结果在半球空间内具有很强一致性,在多尺度实测数据也简洁验证了模型关系的稳定性,模型R2普遍高于0.9.相比于现存植被偏振反射模型,本文构建的模型兼具物理机理、简洁形式、可接受的参数化方案、较高精度和较强泛化能力,对浓密植被具备通用性,为在BRDF一维标量遥感的基础上进一步考虑BPDF二维偏振特性从而形成矢量遥感体系这一转变过程提供了理论基础和探索性方案.

关键词：植被 BPDF 矢量遥感物理模型偏振

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Inflammasome links traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease

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Neural Regeneration Research 2025年第6期20卷 1644-1664页

作者： Gabriela Seplovich Yazan Bouchi Juan Pablo de Rivero Vaccari Jennifer C.Munoz Pareja Andrew Reisner Laura Blackwell Yehia Mechref kevin K.Wang J.Adrian Tyndall Binu Tharakan Firas Kobeissy Department of Surgery Morehouse School of MedicineAtlantaGAUSA Department of Neurobiology Center for NeurotraumaMultiomics&Biomarkers(CNMB)Neuroscience InstituteMorehouse School of MedicineAtlantaGAUSA Department of Neurological Surgery and the Miami Project to Cure Paralysis University of Miami Miller School of MedicineMiamiFLUSA Division of Pediatric Critical Care Department of PediatricsUniversity of Miami Miller School of MedicineMiamiFLUSA Department of Pediatrics Emory UniversityAtlantaGAUSA Department of Neurosurgery Children’s Healthcare of AtlantaAtlantaGAUSA Department of Chemistry and Biochemistry Texas Tech UniversityLubbockTXUSA Morehouse School of Medicine AtlantaGAUSA

Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela of neuroinflammation includes the pathologic hyperphosphorylation of tau protein, an endogenous microtubule-associated protein that protects the integrity of neuronal cytoskeletons. Tau hyperphosphorylation results in protein misfolding and subsequent accumulation of tau tangles forming neurotoxic aggregates. These misfolded proteins are characteristic of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease and can lead to downstream neuroinflammatory processes, including assembly and activation of the inflammasome complex. Inflammasomes refer to a family of multimeric protein units that, upon activation, release a cascade of signaling molecules resulting in caspase-induced cell death and inflammation mediated by the release of interleukin-1β cytokine. One specific inflammasome, the NOD-like receptor protein 3, has been proposed to be a key regulator of tau phosphorylation where it has been shown that prolonged NOD-like receptor protein 3 activation acts as a causal factor in pathological tau accumulation and spreading. This review begins by describing the epidemiology and pathophysiology of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease. Next, we highlight neuroinflammation as an overriding theme and discuss the role of the NOD-like receptor protein 3 inflammasome in the formation of tau deposits and how such tauopathic entities spread throughout the brain. We then propose a novel framework linking traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease as inflammasomedependent pathologies that exist along a temporal continuum. Finally, we discuss potential therapeutic targets that may intercept this pathway and ultimately minimize long-term neurological decline.

关键词： Alzheimer's disease caspase-1 chronic traumatic encephalopathy inflammasomes neurodegeneration neuroinflammation NLRP1 NLRP3 pyroptosis tauopathy traumatic brain injury

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Canonical and noncanonical Wnt signaling: Multilayered mediators, signaling mechanisms and major signaling crosstalk

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Genes & Diseases 2024年第1期11卷 103-134页

作者： kevin Qin Michael Yu Jiaming Fan Hongwei Wang Piao Zhao Guozhi Zhaoo Wei Zeng Connie Chen Yonghui Wang Annie Wang Zander Schwartz Jeffrey Hong Lily Song William Wagstaff Rex C.Haydon Hue H.Luu Sherwin H.Ho Jason Strelzow Russell R.Reid Tong-Chuan He Lewis L.Shi Chicago Medical School Rosalind Franklin University of Medicine and ScienceNorth ChicagoIL 60064USA Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Ministry of Education Key Laboratory of Diagnostic Medicine and Department of Clinical BiochemistryThe School of Laboratory MedicineChongqing Medical UniversityChongqing 400016China Departments of Orthopaedic Surgery and Urology The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Interventional Neurology The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguanGuangdong 523475China Department of Clinical Laboratory Medicine Shanghai Jiaotong University School of MedicineShanghai 200000China School of Biomedical Engineering Vanderbilt UniversityNashvilleTN 37235USA Laboratory of Craniofacial Biology and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA

Wnt signaling plays a major role in regulating cell proliferation and *** Wnt ligands are a family of 19 secreted glycoproteins that mediate their signaling effects via binding to Frizzled receptors and LRP5/6 coreceptors and transducing the signal either throughβ-catenin in the canonical pathway or through a series of other proteins in the nonca-nonical *** of the individual components of both canonical and noncanonical Wnt signaling have additional functions throughout the body,establishing the complex interplay between Wnt signaling and other signaling *** crosstalk between Wnt signaling and other pathways gives Wnt signaling a vital role in many cellular and organ ***-regulation of this system has been implicated in many diseases affecting a wide array of organ systems,including cancer and embryological defects,and can even cause embryonic *** complexity of this system and its interacting proteins have made Wnt signaling a target for many therapeutic ***,both stimulatory and inhibitory treatments come with potential risks that need to be *** review synthesized much of the current knowl-edge on the Wnt signaling pathway,beginning with the history of Wnt *** thoroughly described the different variants of Wnt signaling,including canonical,noncanonical Wnt/PCP,and the noncanonical Wnt/Ca2+*** description involved each of its components and their involvement in other cellular ***,this review explained the various other pathways and processes that crosstalk with Wnt signaling.

关键词： β-catenin Canonical Wnt Noncanonical Wnt Signal transduction Signaling crosstalk

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Tensorial tomographic Fourier ptychography with applications to muscle tissue imaging

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Advanced Photonics 2024年第2期6卷 50-60页

作者： Shiqi Xu Xi Yang Paul Ritter Xiang Dai Kyung Chul Lee Lucas Kreiss kevin C.Zhou Kanghyun Kim Amey Chaware Jadee Neff Carolyn Glass Seung Ah Lee Oliver Friedrich Roarke Horstmeyer Duke University DurhamNorth CarolinaUnited States Friedrich-Alexander University ErlangenGermany UC San Diego La JollaCaliforniaUnited States Yonsei University SeoulRepublic of Korea UC Berkeley BerkeleyCaliforniaUnited States Duke University Medical Center DurhamNorth CarolinaUnited States

We report tensorial tomographic Fourier ptychography(T^(2)oFu),a nonscanning label-free tomographic microscopy method for simultaneous imaging of quantitative phase and anisotropic specimen information in *** upon Fourier ptychography,a quantitative phase imaging technique,T^(2)oFu additionally highlights the vectorial nature of *** imaging setup consists of a standard microscope equipped with an LED matrix,a polarization generator,and a polarization-sensitive *** tensors of anisotropic samples are computationally recovered from polarized intensity measurements across three *** demonstrate T^(2)oFu’s efficiency through volumetric reconstructions of refractive index,birefringence,and orientation for various validation samples,as well as tissue samples from muscle fibers and diseased heart *** reconstructions of healthy muscle fibers reveal their 3D fine-filament structures with consistent ***,we demonstrate reconstructions of a heart tissue sample that carries important polarization information for detecting cardiac amyloidosis.

关键词： computational imaging three-dimensional imaging phase retrieval microscopy polarization-sensitive imaging labelfree imaging

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Mixed ion and electron transport theory and application in solid oxide conductors

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International Journal of Minerals,Metallurgy and Materials 2022年第4期29卷 870-875页

作者： kevin Huang Department of Mechanical engineering University of South CarolinaColumbiaSC 292201USA

Mixed ions and electron conductors(MIECs)are an important family of electrocatalysts for electrochemical devices,such as reversible solid oxide cells,rechargeable metal-air batteries,and oxygen transport *** ionic and electronic transports in these materials play a key role in electrocatalytic *** in-depth fundamental understanding of the transport phenomena is critically needed to develop better *** this brief review,we introduced generic ionic and electronic transport theory based on irreversible thermodynamics and applied it to practical oxide-based materials with oxygen vacancies and electrons/holes as the predominant *** oxide systems,namely CeO_(2)-based and La CrO_(3)-based materials,are selected as case studies to illustrate the utility of the transport theory in predicting oxygen partial pressure distribution across MIECs,electrochemical electronic/ionic leakage currents,and the effects of external load current on the leakage currents.

关键词： irreversible thermodynamics diffusivity charge neutrality electrochemical potential electrostatic potential

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Surgical Treatment of Osteonecrosis of the Femoral Head Using Minimally Invasive Surgical Drilling and Cancellous Grafting at Brazzaville University Hospital

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Open Journal of Orthopedics 2024年第2期14卷 122-132页

作者： kevin Parfait Bienvenu Bouhelo-Pam Marius Monka Arnauld Sledje Wilfrid Bilongo Bouyou Regis Perry Massouama Paul Yèlai Ikounga Roger Bertrand Sah Mbou Armand Moyikoua Department of Orthopaedic surgery and Traumatology University Hospital of Brazzaville Brazzaville Republic of the Congo Faculty of Health Sciences Marien N’GOUABI University Brazzaville Republic of the Congo

Introduction: Osteonecrosis of the femoral head (ONTF) is a debilitating condition. Several treatments have been proposed with controversial results. The aim of our study was to evaluate treatment by surgical drilling coupled with in situ cancellous grafting. Materials and methods: Our study was a case-control study conducted at Brazzaville University Hospital from 1st January 2018 to 31 December 2023. It compared two groups of patients with ONTF: non-operated (13 patients, 20 hips) and operated (22 patients, 35 hips). We used the visual digital scale (VDS) for pain assessment, the Merle D’Aubigne-Postel (MDP) scoring system for clinical and functional assessment, and the evolution of necrosis. Results: The group of non-operated patients had a mean age of 35.69 ± 3.4 years, no improvement in pain with an EVN above seven at the last recoil and a mean global MDP score falling from 12.7 before offloading to 10.13 at one year. The group of patients operated on had a mean age of 37.86 ± 7.02 years, a significant reduction in pain (p = 0.00004) and a significantly increased MDP score (p = 0.0034). A comparison of the two groups of patients showed significant stabilization of the necrotic lesions in the operated patients (p = 0.00067), with better satisfaction in the same group. Conclusion: Surgical drilling combined with grafting in the treatment of early-stage ONTF has improved progress in our series. The technique is reproducible and less invasive. It has made it possible to delay unfavorable progression and, consequently, hip replacement surgery.

关键词： Hip Osteonecrosis of the Femoral Head Conservative Treatment Surgical Drilling Bone Grafting

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