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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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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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Fatal risk in hysteroscopic surgery that should not be overlooked:Uterine artery pseudoaneurysm

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World Journal of Clinical Cases 2025年第8期13卷 53-56页

作者： Mi-Si He Ke-Xiao Yu Chen Wang Department of Gynecologic Oncology Chongqing University Cancer Hospital and Chongqing Cancer Institute and Chongqing Cancer HospitalChongqing 400030China Department of orthopedics Chongqing Hospital of Traditional Chinese MedicineChongqing 400021China

This article provides a detailed account of the diagnosis and treatment of a case involving a uterine artery pseudoaneurysm(UAP),as well as an analysis of UAP *** finding emphasizes that UAP should be considered in patients presenting with abnormal genital bleeding after hysteroscopy and offers valuable insights and lessons for gynecologists in hysteroscopic *** patient underwent timely relevant examinations to confirm the diagnosis,allowing for crucial time required for her *** this study,the primary cause of UAP formation in the patient was attributed to a prior hysteroscopic surgical procedure conducted at another medical facility,suggesting that the selection and imple-mentation of dilatation catheters are some of the predisposing factors for *** conclusion,this case study offers a comprehensive analysis of the etiology of UAP and effectively provides timely diagnosis and treatment,offering valuable in-sights for the clinical diagnosis and management of UAP.

关键词： Editorial Uterine artery pseudoaneurysm Case report Hysteroscopic surgery Uterine arteriovenous malformations

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Nanocarrier-mediated siRNA delivery:a new approach for the treatment of traumatic brain injury-related Alzheimer's disease

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Neural Regeneration Research 2025年第9期20卷 2538-2555页

作者： Jie Jin Huajing Zhang Qianying Lu Linqiang Tian Sanqiao Yao Feng Lai Yangfan Liang Chuanchuan Liu Yujia Lu Sijia Tian Yanmei Zhao Wenjie Ren institute of Disaster and Emergency Medicine Tianjin UniversityTianjinChina Key Laboratory for Disaster Medicine Technology TianjinChina Henan Medical Key Laboratory for Research of Trauma and orthopedics The Third Affiliated Hospital of Xinxiang Medical UniversityXinxiangHenan ProvinceChina Clinical Medical Center of Tissue Engineering and Regeneration Xinxiang Medical UniversityXinxiangHenan ProvinceChina institutes of Health Central Plain Xinxiang Medical UniversityXinxiangHenan ProvinceChina School of Public Health Xinxiang Medical UniversityXinxiangHenan ProvinceChina

Traumatic brain injury and Alzheimer's disease share pathological similarities,including neuronal loss,amyloid-βdeposition,tau hyperphosphorylation,blood-brain barrier dysfunction,neuroinflammation,and cognitive ***,traumatic brain injury can exacerbate Alzheimer's disease-like pathologies,potentially leading to the development of Alzheimer's *** offer a potential solution by facilitating the delive ry of small interfering RNAs across the blood-brain barrier for the targeted silencing of key pathological genes implicated in traumatic brain injury and Alzheimer's disease.U nlike traditional approaches to neuro regeneration,this is a molecula r-targeted strategy,thus avoiding non-specific drug *** review focuses on the use of nanocarrier systems for the efficient and precise delive ry of siRNAs,discussing the advantages,challenges,and future *** principle,siRNAs have the potential to target all genes and non-targetable protein s,holding significant promise for treating various *** the various therapeutic approaches currently available for neurological diseases,siRNA gene silencing can precisely"turn off"the expression of any gene at the genetic level,thus radically inhibiting disease progression;however,a significant challenge lies in delivering siRNAs across the blood-brain *** have received increasing attention as an innovative drug delive ry tool fo r the treatment of brain *** are considered a potential therapeutic strategy with the advantages of being able to cross the blood-brain barrier,targeted drug delivery,enhanced drug stability,and multifunctional *** use of nanoparticles to deliver specific modified siRNAs to the injured brain is gradually being recognized as a feasible and effective *** this strategy is still in the preclinical exploration stage,it is expected to achieve clinical translation in the future,creating a new field of molecular tar

关键词： blood-brain barrier cognitive dysfunction exosomes gene silencing immunotherapy inorganic nanomaterials liposome nanoparticles neuroinflammation polymer nanoparticles stem cells

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Crystallodiagnostics of some animals' helmintosis

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Asian Pacific Journal of Tropical Medicine 2010年第3期3卷 176-179页

作者： Andrew Martusevich Grishina AA Bochkareva AV Laboratory of Physical and Chemical Medicine Institute of Traumatology and Orthopedics

Objective:To investigate the teziocrystalloscopic features of urine which were collected from both healthy rodents and those with ***:Physical-chemical characteristics of urine samples that were collected from 15 mice and 20 rats were estimated by their ability to *** test results were interpreted with integrated identity table which includes 5 main classes of the crystalline and amorphous *** quantitative and semiquantitative evaluation indicators were also ***:Presence of Trichinella spiralis in animal organism transformed results of the biofluid free *** main components of rats’ urine facia were single-crystalline rectangles which were made of cholesterol and its *** biofluid microsamples of healthy rats and rats with echinococcosis had both common and ***:Urine teziocrystalloscopic analysis is an informative method for diagnosis of helminthiasis in animals.

关键词： Biocrystallomics Trichinosis Echinococcosis Crystallodiagnostics Urine

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Resting-state brain network remodeling after different nerve reconstruction surgeries:a functional magnetic resonance imaging study in brachial plexus injury rats

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Neural Regeneration Research 2025年第5期20卷 1495-1504页

作者： Yunting Xiang Xiangxin Xing Xuyun Hua Yuwen Zhang Xin Xue Jiajia Wu Mouxiong Zheng He Wang Jianguang Xu School of Rehabilitation Science Shanghai University of Traditional Chinese MedicineShanghaiChina Engineering Research Center of Traditional Chinese Medicine Intelligent Rehabilitation Ministry of EducationShanghaiChina Department of Rehabilitation Medicine Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghaiChina Department of Traumatology and orthopedics Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghaiChina institute of Science and Technology for Brain-Inspired Intelligence Fudan UniversityShanghaiChina Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence(Fudan University) Ministry of EducationShanghaiChina Human Phenome institute Fudan UniversityShanghaiChina

Distinct brain remodeling has been found after different nerve reconstruction strategies,including motor representation of the affected ***,differences among reconstruction strategies at the brain network level have not been *** study aimed to explore intranetwork changes related to altered peripheral neural pathways after different nerve reconstruction surgeries,including nerve repair,endto-end nerve transfer,and end-to-side nerve ***–Dawley rats underwent complete left brachial plexus transection and were divided into four equal groups of eight:no nerve repair,grafted nerve repair,phrenic nerve end-to-end transfer,and end-to-side transfer with a graft sutured to the anterior upper ***-state brain functional magnetic resonance imaging was obtained 7 months after *** independent component analysis algorithm was utilized to identify group-level network components of interest and extract resting-state functional connectivity values of each voxel within the *** in intra-network resting-state functional connectivity were compared among the *** muscle reinnervation was assessed by behavioral observation(elbow flexion)and *** results showed that alterations in the sensorimotor and interoception networks were mostly related to changes in the peripheral neural *** repair was related to enhanced connectivity within the sensorimotor network,while end-to-side nerve transfer might be more beneficial for restoring control over the affected limb by the original motor *** thalamic-cortical pathway was enhanced within the interoception network after nerve repair and end-to-end nerve *** areas related to cognition and emotion were enhanced after end-to-side nerve *** study revealed important brain networks related to different nerve *** networks may be potential targets for enhancing motor recovery.

关键词： brain functional networks end-to-end nerve transfer end-to-side nerve transfer independent component analysis nerve repair peripheral plexus injury resting-state functional connectivity

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Jisuikang, a Chinese herbal formula, increases neurotrophic factor expression and promotes the recovery of neurological function after spinal cord injury

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Neural Regeneration Research 2017年第9期12卷 1519-1528页

作者： Yang Guo Yong Ma Ya-lan Pan Su-yang Zheng Jian-wei Wang Gui-cheng Huang institute of Traumatology & orthopedics and Laboratory of New Techniques of Restoration & Reconstruction of orthopedics and Traumatology Nanjing University of Chinese Medicine Department of Traumatology & orthopedics Affiliated Hospital of Nanjing University of Chinese Medicine Department of Traumatology & orthopedics Wuxi Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Chinese Medicine

The Chinese medicine compound, ]isuikang, can promote recovery of neurological function by inhibiting lipid peroxidation, scavenging oxygen free radicals, and effectively improving the local microenvironment after spinal cord injury. However, the mechanism remains unclear. Thus, we established a rat model of acute spinal cord injury using a modified version of Allen＇s method. Jisuikang （50, 25, and 12.5 g/kg/d） and prednis- olone were administered 30 minutes after anesthesia. Basso, Beattie, and Bresnahan locomotor scale scores and the oblique board test showed improved motor function recovery in the prednisone group and moderate-dose Jisuikang group compared with the other groups at 3-7 days post-injury. The rats in the moderate-dose Jisuikang group recovered best at 14 days post-injury. Hematoxylin-eosin staining and transmis- sion electron microscopy showed that the survival rate of neurons in treatment groups increased after 3-7 days of administration. Further, the structure of neurons and glial cells was more distinct, especially in prednisolone and moderate-dose Jisuikang groups. Western blot assay and immunohistochemistry showed that expression of brain-derived neurotrophic factor （BDNF） in injured segments was maintained at a high level after 7-14 days of treatment. In contrast, expression of nerve growth factor （NGF） was down-regulated at 7 days after spinal cord injury. Re- al-time fluorescence quantitative polymerase chain reaction showed that expression of BDNF and NGF mRNA was induced in injured segments by prednisolone and Jisuikang. At 3-7 days after injury, the effect of prednisolone was greater, while 14 days after injury, the effect of moder- ate-dose Jisuikang was greater. These results confirm that Jisuikang can upregulate BDNF and NGF expression for a prolonged period after spinal cord injury and promote repair of acute spinal cord injury, with its effect being similar to prednisolone.

关键词： nerve regeneration spinal cord injury Jisuikang Chinese medicine prednisolone microenvironment axon regeneration secondary changes neuronal apoptosis brain-derived neurotrophic factor nerve growth factor neural regeneration

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Effect of Zuogui pill and Yougui pill on osteoporosis： a randomized controlled trial

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Journal of Traditional Chinese Medicine 2018年第1期38卷 33-42页

作者： Li Wenxiong Zhang Kuaiqiang Liu Zhu Liu Li Cheng Yan Yin Jichao Sun Yindi Yang Feng institute of orthopedics Shaanxi University of Traditional Chinese Medicine Xi'an 712000 China Department of orthopedics Affiliated Hospital of Shaanxi University of Traditional Chinese Medicine Xi'an 712083 China Department of orthopedics Shaanxi Province Hospital of TCM Xi'an 710021 China Department of orthopedics Xi'an Hospital of TCM Xi'an 710021 China Department of orthopedics Xi'an Honghui Hospital Xi'an 710021 China

OBJECTIVE： To evaluate the effect and safety of Zuogui pill and Yougui pill, classic Y/n and Yang tonic formula （CYYTF）, in the treatment of osteoporosis and the underlying mechanism. METHODS： Participants aged 55 to 75 with osteoporosis and Kidney deficiency in Traditional Chi-nese Medicine （TCM） will be included and randomly allocated into two groups： treatment group and control group. Participants in the treatment group were treated with Zuogui pill or Yougui pill TCM formula granule, while the control group received pla- cebo. Primary outcomes are the lumbar spine on bone mineral density （BMD）（L1-4） and femoral BMD. Secondary outcomes include pain intensity, health-related quality of life （HRQoL）, bone turn- over markers and safety. RESULTS： Totally 200 patients were enrolled from December 2014 to April 2016 from four hospitals. There were no statistically significant differences between the two groups at baseline （P 〉 0.05） and it was good to comparability. Statistically signifi- cant differences between the two groups were ob- served for the lumbar BMD （L1-4）, pain VAS scores and HRQoL at six months and twelve months and femoral BMD at twelve months （P 〈 0.05）, but no significant differences for femoral BMD and bone turnover markers at six months （P 〉 0.05）. More- over, significant difference was observed at differ- ent time before and after treatment in terms of lum- bar spine （L1-4） BMD, femoral BMD, pain VAS scores and health-related quality of life, and there was an crossover effect between the time and groups be- fore and after treatment. In additional, in the treat- ment group, 8 patients lost to follow-up and 3 patients had adverse events （AEs） and in the control group, 10 patients lost to follow-up and 2 patients had AEs. No remarkable differences were observed between the two groups with regard to AEs, lost rate and safety （P 〉 0.05）. CONCLUSION： Zuogui pill or Yougui pill could improve BMD, ease pain, relieve Kidney deficiencysyndrome, improve the q

关键词： Bone resorption Osteoporosis Zuo Gui Wan You Gui Wan Treatment outcome Quality of life

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Superenhancers activate the autophagy-related genes Beclin1 and LC3B to drive metastasis and drug resistance in osteosarcoma

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Frontiers of Medicine 2022年第6期16卷 883-895页

作者： Hongyi Wang Zhuochao Liu Jun Wang Fangqiong Hu Qi Zhou Li Wei Qiyuan Bao Jizhuang Wang Jing Liang Zhihong Liu Weibin Zhang Department of orthopedics Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai200025China Shanghai institute of Traumatology and orthopedics Shanghai200025China

Metastasis and drug resistance are the leading causes of poor prognosis in patients with *** the relevant factors that drive metastasis and drug resistance is the key to improving the therapeutic outcome of ***,we reported that autophagy was highly activated in metastatic *** found increased autophagolysosomes in metastatic osteosarcoma cell lines by using electron microscopy,Western blot,and immunofluorescence *** further examined the expression of the autophagy-related genes Beclin1 and LC3B in 82 patients through immunohistochemistry and found that Beclin1 and LC3B were highly related to unfavorable prognosis of *** of Beclin1 and LC3B reduced invasion,metastasis,and proliferation in metastatic osteosarcoma *** vitro and in vivo studies also demonstrated that inhibiting by 3-MA inhibited cell growth and ***,we demonstrated that autophagy-related genes were activated by SEs and that the inhibition of SEs by JQ-1 decreased the metastasis of ***,our findings highlighted the association of autophagy with osteosarcoma progression and shed new light on autophagy-targeting therapy for osteosarcoma.

关键词： osteosarcoma autophagy metastasis drug resistance Beclin1 LC3B

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Cytotoxic Effect on Osteosarcoma MG-63 Cells by Degradation of Magnesium

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Journal of Materials Science & Technology 2014年第9期30卷 888-893页

作者： Mei Li Ling Ren LiHua Li Peng He GuoBo Lan Yu Zhang Ke Yang Hospital of orthopedics Guangzhou General Hospital of Guangzhou Military Command institute of Metal Research Chinese Academy of Sciences

Biocompatible and biodegradable magnesium （Mg） based metals have attracted great interest for use in orthopedic implants and devices. Based on our previous study that Mg with and without micro-arc oxidation （MAO） coating showed obvious cytotoxic effect on tumor cells due to the increase of pH value during the degradation of Mg, this study further evaluated the cytotoxic effect of Mg and MAO coated Mg on osteosarcoma （MG-63） cells by analyzing the cell adhesion, morphology and number through observation of scanning electron microscope, as well as live/dead staining, lactate dehydrogenase （LDH） activity and 4, 6- diamidino-2-phenylindole （DAPI） assay. The results indicated that, compared to titanium, Mg could strongly inhibit the cell adherence, morphology and number of MG-63 on the surface of the naked Mg, whereas the MAO coated Mg showed relative weak cytotoxic effect on MG-63 cells, expecting that magnesium based metals with suitable coating can be designed to be applied as tumor prosthesis in the clinical practice.

关键词： Magnesium Biodegradation Osteosarcoma Cytotoxicity

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