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Inhibiting SHP2 reduces glycolysis, promotes microglial M1 polarization, and alleviates secondary inflammation following spinal cord injury in a mouse model

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Neural Regeneration Research 2025年第3期20卷 858-872页

作者： Xintian Ding Chun Chen Heng Zhao Bin Dai Lei Ye Tao Song Shuai Huang Jia Wang Tao You department of orthopedics The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui ProvinceChina department of orthopedics Provincial Hospital Affiliated to Anhui Medical UniversityHefeiAnhui ProvinceChina

Reducing the secondary inflammatory response, which is partly mediated by microglia, is a key focus in the treatment of spinal cord injury. Src homology 2-containing protein tyrosine phosphatase 2(SHP2), encoded by PTPN11, is widely expressed in the human body and plays a role in inflammation through various mechanisms. Therefore, SHP2 is considered a potential target for the treatment of inflammation-related diseases. However, its role in secondary inflammation after spinal cord injury remains unclear. In this study, SHP2 was found to be abundantly expressed in microglia at the site of spinal cord injury. Inhibition of SHP2 expression using siRNA and SHP2 inhibitors attenuated the microglial inflammatory response in an in vitro lipopolysaccharide-induced model of inflammation. Notably, after treatment with SHP2 inhibitors, mice with spinal cord injury exhibited significantly improved hind limb locomotor function and reduced residual urine volume in the bladder. Subsequent in vitro experiments showed that, in microglia stimulated with lipopolysaccharide, inhibiting SHP2 expression promoted M2 polarization and inhibited M1 polarization. Finally, a co-culture experiment was conducted to assess the effect of microglia treated with SHP2 inhibitors on neuronal cells. The results demonstrated that inflammatory factors produced by microglia promoted neuronal apoptosis, while inhibiting SHP2 expression mitigated these effects. Collectively, our findings suggest that SHP2 enhances secondary inflammation and neuronal damage subsequent to spinal cord injury by modulating microglial phenotype. Therefore, inhibiting SHP2 alleviates the inflammatory response in mice with spinal cord injury and promotes functional recovery postinjury.

关键词： apoptosis glycolysis inflammatory response microglia neurons polarization spinal cord injury Src homology 2-containing protein tyrosine phosphatase 2

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A novel flexible nerve guidance conduit promotes nerve regeneration while providing excellent mechanical properties

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Neural Regeneration Research 2025年第7期20卷 2084-2094页

作者： Tong Li Quhan Cheng Jingai Zhang Boxin Liu Yu Shi Haoxue Wang Lijie Huang Su Zhang Ruixin Zhang Song Wang Guangxu Lu Peifu Tang Zhongyang Liu Kai Wang department of orthopedics the Fourth Medical Center of Chinese PLA General HospitalBeijingChina department of Training and Sports Medicine Characteristic Medical Center of Chinese People’s Armed Police ForceTianjinChina Medical School of Chinese PLA BeijingChina Key Laboratory of Bioactive Materials for the Ministry of Education College of Life SciencesNankai UniversityTianjinChina department of orthopedics Tianjin HospitalTianjinChina department of Rehabilitation Medicine Er Quan Hospital of PAPWuxiJiangsu ProvinceChina

Autografting is the gold standard for surgical repair of nerve defects>5 mm in length;however,autografting is associated with potential complications at the nerve donor *** an alternative,nerve guidance conduits may be *** ideal conduit should be flexible,resistant to kinks and lumen collapse,and provide physical cues to guide nerve *** designed a novel flexible conduit using electrospinning technology to create fibers on the innermost surface of the nerve guidance conduit and employed melt spinning to align ***,we prepared disordered electrospun fibers outside the aligned fibers and helical melt-spun fibers on the outer wall of the electrospun fiber *** presence of aligned fibers on the inner surface can promote the extension of nerve cells along the *** helical melt-spun fibers on the outer surface can enhance resistance to kinking and compression and provide *** novel conduit promoted nerve regeneration and functional recovery in a rat sciatic nerve defect model,suggesting that it has potential for clinical use in human nerve injuries.

关键词： aligned fibers anti-kinking helical fibers nerve guidance conduit nerve regeneration peripheral nerve injury topological guidance

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An Enhanced Lung Cancer Detection Approach Using Dual-Model Deep Learning Technique

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Computer Modeling in Engineering & Sciences 2025年第1期142卷 835-867页

作者： Sumaia Mohamed Elhassan Saad Mohamed Darwish Saleh Mesbah Elkaffas department of information Technology Institute of Graduate Studies and ResearchAlexandria UniversityAlexandria21526Egypt College of Computing and information Technology Arab Academy for ScienceTechnology and Maritime TransportAlexandriaP.O.Box 1029Egypt

Lung cancer continues to be a leading cause of cancer-related deaths worldwide,emphasizing the critical need for improved diagnostic *** detection of lung tumors significantly increases the chances of successful treatment and ***,current diagnostic methods often fail to detect tumors at an early stage or to accurately pinpoint their location within the lung ***-model deep learning technologies for lung cancer detection,while beneficial,cannot capture the full range of features present in medical imaging data,leading to incomplete or inaccurate ***,it may not be robust enough to handle the wide variability in medical images due to different imaging conditions,patient anatomy,and tumor *** overcome these disadvantages,dual-model or multi-model approaches can be *** research focuses on enhancing the detection of lung cancer by utilizing a combination of two learning models:a Convolutional Neural Network(CNN)for categorization and the You Only Look Once(YOLOv8)architecture for real-time identification and pinpointing of *** automatically learn to extract hierarchical features from raw image data,capturing patterns such as edges,textures,and complex structures that are crucial for identifying lung ***8 incorporates multiscale feature extraction,enabling the detection of tumors of varying sizes and scales within a single *** is particularly beneficial for identifying small or irregularly shaped tumors that may be challenging to ***,through the utilization of cutting-edge data augmentation methods,such as Deep Convolutional Generative Adversarial Networks(DCGAN),the suggested approach can handle the issue of limited data and boost the models’ability to learn from diverse and comprehensive *** combined method not only improved accuracy and localization but also ensured efficient real-time processing,which is crucial for practical clinical applicati

关键词： Lung cancer detection dual-model deep learning technique data augmentation CNN YOLOv8

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Congruent Feature Selection Method to Improve the Efficacy of Machine Learning-Based Classification in Medical Image Processing

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Computer Modeling in Engineering & Sciences 2025年第1期142卷 357-384页

作者： Mohd Anjum Naoufel Kraiem Hong Min Ashit Kumar Dutta Yousef Ibrahim Daradkeh department of Computer Engineering Aligarh Muslim UniversityAligarh202002India College of Computer Science King Khalid UniversityAbha61413Saudi Arabia School of Computing Gachon UniversitySeongnam13120Republic of Korea department of Computer Science and information Systems College of Applied SciencesAlMaarefa UniversityRiyadh13713Saudi Arabia department of Computer Engineering and information College of Engineering in Wadi AlddawasirPrince Sattam bin Abdulaziz UniversityAl-Kharj16273Saudi Arabia

Machine learning(ML)is increasingly applied for medical image processing with appropriate learning *** applications include analyzing images of various organs,such as the brain,lung,eye,etc.,to identify specific flaws/diseases for *** primary concern of ML applications is the precise selection of flexible image features for pattern detection and region *** of the extracted image features are irrelevant and lead to an increase in computation ***,this article uses an analytical learning paradigm to design a Congruent Feature Selection Method to select the most relevant image *** process trains the learning paradigm using similarity and correlation-based features over different textural intensities and pixel *** similarity between the pixels over the various distribution patterns with high indexes is recommended for disease ***,the correlation based on intensity and distribution is analyzed to improve the feature selection ***,the more congruent pixels are sorted in the descending order of the selection,which identifies better regions than the ***,the learning paradigm is trained using intensity and region-based similarity to maximize the chances of ***,the probability of feature selection,regardless of the textures and medical image patterns,is *** process enhances the performance of ML applications for different medical image *** proposed method improves the accuracy,precision,and training rate by 13.19%,10.69%,and 11.06%,respectively,compared to other models for the selected *** mean error and selection time is also reduced by 12.56%and 13.56%,respectively,compared to the same models and dataset.

关键词： Computer vision feature selection machine learning region detection texture analysis image classification medical images

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Masquelet technique using an allogeneic cortical bone graft for a large bone defect:A case report

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World Journal of Clinical Cases 2025年第5期13卷 36-43页

作者： Hai-Yang Zong Yu Liu Xing Yin Wei Zhou Nan Li department of orthopedics The People’s Liberation Army Joint Logistic Support Force 920th HospitalKunming 650032Yunnan ProvinceChina department of orthopedics 96603 Military Hospital of PLAHuaihua 418000Hunan ProvinceChina

BACKGROUND The induced-membrane technique was initially described by Masquelet as an effective treatment for large bone defects,especially those caused by ***,we report a case of chronic osteomyelitis of the radius associated with a 9 cm bone defect,which was filled with a large allogeneic cortical bone graft from a bone *** bony union was achieved after 14 months of *** studies have used autogenous bone as the primary bone source for the Masquelet technique;in our case,the exclusive use of allografts is as successful as the use of autologous bone *** the advent of bone banks,it is possible to obtain an unlimited amount of allograft,and the Masquelet technique may be further improved based on this new way of bone *** SUMMARY In this study,we reported a case of repair of a long bone defect in a 40-year-old male patient,which was characterized by the utilization of allograft cortical bone combined with the Masquelet technique for the treatment of the patient's long bone defect in the *** patient's results of functional recovery of the forearm were surprising,which further deepens the scope of application of Masquelet technique and helps to strengthen the efficacy of Masquelet technique in the treatment of long bones *** Allograft cortical bone combined with the Masquelet technique provides a new method of treatment to large bone defect.

关键词： Osteomyelitis Bone defect Allogeneic cortical bone Masquelet technique Membrane induction technique Case report

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Advances in therapies using mesenchymal stem cells and their exosomes for treatment of peripheral nerve injury:state of the art and future perspectives

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Neural Regeneration Research 2025年第11期20卷 3151-3171页

作者： Fatima Aldali Chunchu Deng Mingbo Nie Hong Chen department of Rehabilitation Medicine Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina department of orthopedics Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina

“Peripheral nerve injury”refers to damage or trauma affecting nerves outside the brain and spinal *** nerve injury results in movements or sensation impairments,and represents a serious public health *** severed peripheral nerves have been effectively joined and various therapies have been offered,recovery of sensory or motor functions remains limited,and efficacious therapies for complete repair of a nerve injury remain *** emerging field of mesenchymal stem cells and their exosome-based therapies hold promise for enhancing nerve regeneration and *** stem cells,as large living cells responsive to the environment,secrete various factors and *** latter are nano-sized extracellular vesicles containing bioactive molecules such as proteins,microRNA,and messenger RNA derived from parent mesenchymal stem *** have pivotal roles in cell-to-cell communication and nervous tissue function,offering solutions to changes associated with cell-based *** ongoing investigations,mesenchymal stem cells and mesenchymal stem cell-derived exosome-based therapies are in the exploratory stage.A comprehensive review of the latest preclinical experiments and clinical trials is essential for deep understanding of therapeutic strategies and for facilitating clinical *** review initially explores current investigations of mesenchymal stem cells and mesenchymal stem cell-derived exosomes in peripheral nerve injury,exploring the underlying ***,it provides an overview of the current status of mesenchymal stem cell and exosomebased therapies in clinical trials,followed by a comparative analysis of therapies utilizing mesenchymal stem cells and ***,the review addresses the limitations and challenges associated with use of mesenchymal stem cell-derived exosomes,offering potential solutions and guiding future directions.

关键词： clinical trials exosome extracellular vesicles mesenchymal stem cells nerve regeneration peripheral nerve injury pre-clinical experiments

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Correlation between anxiety, depression, and social stress in young patients with thoracolumbar spine fractures

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World Journal of Psychiatry 2025年第1期15卷 83-92页

作者： Bo Wang Da Shi Yin-Di Sun Bo Dong Joint Ward of orthopedics department of TCM Honghui HospitalXi'an Jiaotong UniversityXi’an 710054Shaanxi ProvinceChina Pain Ward of orthopedics department of TCM Honghui HospitalXi'an Jiaotong UniversityXi’an 710054Shaanxi ProvinceChina

BACKGROUND Traumatic injuries,such as falling,car accidents,and crushing mostly cause spinal fractures in young and middle-aged people,and>50%of them are thoracolumbar *** kind of fracture is easily combined with serious injuries to peripheral nerves and soft tissues,which causes paralysis of the lower limbs if there is no timely rehabilitation *** patients with thoracolumbar fractures find it difficult to recover after the operation,and they are prone to depression,low self-esteem,and other negative *** To investigate the association between anxiety,depression,and social stress in young patients with thoracolumbar spine fractures and the effect on rehabilitation *** This study retrospectively analyzed 100 patients admitted to the orthopedic department of Honghui Hospital,Xi’an Jiaotong University who underwent thoracolumbar spine fracture surgery from January 2022 to June *** general data of the patients were assessed with the Hamilton anxiety scale(HAMA),Hamilton depression scale(HAMD),life events scale,and social support rating scale(SSRS)to identify the correlation between anxiety,depression scores,and social stress and social *** Japanese Orthopedic Association(JOA)was utilized to evaluate the rehabilitation outcomes of the patients and to analyze the effects of anxiety and depression scores on *** According to the scores of HAMD and HAMA in all patients,the prevalence of depression in patients was 39%(39/100),and the prevalence of anxiety was 49%(49/100).Patients were categorized into non-depression(n=61)and depression(n=39),non-anxiety(n=51),and anxiety(n=49)*** significant differences in gender,occupation,Pittsburgh Sleep Quality Index(PSQI)score,and monthly family income were observed between the non-depression and depression groups(P<0.05).A significant difference in occupation and PSQI score was found between the non-anxiety and anxiety *** depression(r=0

关键词： Patients with thoracolumbar fractures Anxiety Depression Social pressure Social support

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FK506 contributes to peripheral nerve regeneration by inhibiting neuroinflammatory responses and promoting neuron survival

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Neural Regeneration Research 2025年第7期20卷 2108-2115页

作者： Yuhui Kou Zongxue Jin Yusong Yuan Bo Ma Wenyong Xie Na Han department of Trauma and orthopedics Peking University People’s HospitalBeijingChina National Center for Trauma Medicine Peking University People’s HospitalBeijingChina Key Laboratory of Trauma and Neural Regeneration(Peking University) Ministry of EducationBeijingChina Trauma Medicine Center Peking University People’s HospitalBeijingChina department of orthopedics China-Japan Friendship HospitalBeijingChina

FK506(Tacrolimus)is a systemic immunosuppressant approved by the *** and Drug ***506 has been shown to promote peripheral nerve regeneration,however,its precise mechanism of action and its pathways remain *** this study,we established a rat model of sciatic nerve injury and found that FK506 improved the morphology of the injured sciatic nerve,increased the numbers of motor and sensory neurons,reduced inflammatory responses,markedly improved the conduction function of the injured nerve,and promoted motor function *** findings suggest that FK506 promotes peripheral nerve structure recovery and functional regeneration by reducing the intensity of inflammation after neuronal injury and increasing the number of surviving neurons.

关键词： FK506 inflammation motor neurons nerve regeneration neuron peripheral nerve injury sensory neurons

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Mutual regulation of microglia and astrocytes after Gas6 inhibits spinal cord injury

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Neural Regeneration Research 2025年第2期20卷 557-573页

作者： Jiewen Chen Xiaolin Zeng Le Wang Wenwu Zhang Gang Li Xing Cheng Peiqiang Su Yong Wan Xiang Li department of Spine Surgery The First Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong ProvinceChina Guangdong Province Key Laboratory of orthopedics and Traumatology GuangzhouGuangdong ProvinceChina

Invasive inflammation and excessive scar formation are the main reasons for the difficulty in repairing nervous tissue after spinal cord *** and astrocytes play key roles in the spinal cord injury micro-environment and share a close ***,the mechanisms involved remain *** this study,we found that after spinal cord injury,resting microglia(M0)were polarized into pro-inflammatory phenotypes(MG1 and MG3),while resting astrocytes were polarized into reactive and scar-forming *** expression of growth arrest-specific 6(Gas6)and its receptor Axl were significantly down-regulated in microglia and astrocytes after spinal cord *** vitro experiments showed that Gas6 had negative effects on the polarization of reactive astrocytes and pro-inflammatory microglia,and even inhibited the cross-regulation between *** further demonstrated that Gas6 can inhibit the polarization of reactive astrocytes by suppressing the activation of the Yes-associated protein signaling ***,in turn,inhibited the polarization of pro-inflammatory microglia by suppressing the activation of the nuclear factor-κB/p65 and Janus kinase/signal transducer and activator of transcription signaling *** vivo experiments showed that Gas6 inhibited the polarization of pro-inflammatory microglia and reactive astrocytes in the injured spinal cord,thereby promoting tissue repair and motor function ***,Gas6 may play a role in the treatment of spinal cord *** can inhibit the inflammatory pathway of microglia and polarization of astrocytes,attenuate the interaction between microglia and astrocytes in the inflammatory microenvironment,and thereby alleviate local inflammation and reduce scar formation in the spinal cord.

关键词： astrocytes Axl cell polarization Gas6 Hippo signal inflammatory micro-environment intercellular interaction microglia single-cell sequencing spinal cord injury

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Metabolic reprogramming: a new option for the treatment of spinal cord injury

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Neural Regeneration Research 2025年第4期20卷 1042-1057页

作者： Jiangjie Chen Jinyang Chen Chao Yu Kaishun Xia Biao Yang Ronghao Wang Yi Li Kesi Shi Yuang Zhang Haibin Xu Xuesong Zhang Jingkai Wang Qixin Chen Chengzhen Liang department of orthopedics The Second Affiliated Hospital of Zhejiang University School of MedicineHangzhouZhejiang ProvinceChina orthopedics Research Institute of Zhejiang University Zhejiang UniversityHangzhouZhejiang ProvinceChina Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province HangzhouZhejiang ProvinceChina Clinical Research Center of Motor System Disease of Zhejiang Province HangzhouZhejiang ProvinceChina Qiandongnan Prefecture People’s Hospital KailiGuizhou ProvinceChina department of orthopedics Fourth Medical CenterChinese PLA General HospitalBeijingChina

Spinal cord injuries impose a notably economic burden on society,mainly because of the severe after-effects they *** the ongoing development of various therapies for spinal cord injuries,their effectiveness remains ***,a deeper understanding of metabolism has opened up a new therapeutic opportunity in the form of metabolic *** this review,we explore the metabolic changes that occur during spinal cord injuries,their consequences,and the therapeutic tools available for metabolic *** spinal cord metabolism is characterized by independent cellular metabolism and intercellular metabolic ***,spinal cord injury results in metabolic disorders that include disturbances in glucose metabolism,lipid metabolism,and mitochondrial *** metabolic disturbances lead to corresponding pathological changes,including the failure of axonal regeneration,the accumulation of scarring,and the activation of *** rescue spinal cord injury at the metabolic level,potential metabolic reprogramming approaches have emerged,including replenishing metabolic substrates,reconstituting metabolic couplings,and targeting mitochondrial therapies to alter cell *** available evidence suggests that metabolic reprogramming holds great promise as a next-generation approach for the treatment of spinal cord *** further advance the metabolic treatment of the spinal cord injury,future efforts should focus on a deeper understanding of neurometabolism,the development of more advanced metabolomics technologies,and the design of highly effective metabolic interventions.

关键词： axons glycolysis metabolic reprogramming metabolism mitochondria neural regeneration neuroprotection oxidative phosphorylation spinal cord injury therapy

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