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Chondroitinase ABC combined with Schwann cell transplantation enhances restoration of neural connection and functional recovery following acute and chronic spinal cord injury

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Neural Regeneration Research 2025年第5期20卷 1467-1482页

作者： Wenrui Qu Xiangbing Wu Wei Wu Ying Wang Yan Sun Lingxiao Deng Melissa Walker Chen Chen Heqiao Dai Qi Han Ying Ding Yongzhi Xia George Smith Rui Li Nai-Kui Liu Xiao-Ming Xu Spinal Cord and Brain Injury Research Group Stark Neurosciences Research InstituteDepartment of Neurological SurgeryIndiana University School of MedicineIndianapolisINUSA Department of Hand surgery the Second Hospital of Jilin UniversityChangchunJilin ProvinceChina Shriners hospitals Pediatric Research center Temple University School of MedicinePhiladelphiaPAUSA Department of Anatomy&Cell Biology Indiana University School of MedicineIndianapolisINUSA

Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties.A the Food and Drug Administration-approved Phase I clinical trial has been conducted to evaluate the safety of transplanted human autologous Schwann cells to treat patients with spinal cord injury.A major challenge for Schwann cell transplantation is that grafted Schwann cells are confined within the lesion cavity,and they do not migrate into the host environment due to the inhibitory barrier formed by injury-induced glial scar,thus limiting axonal reentry into the host spinal *** we introduce a combinatorial strategy by suppressing the inhibitory extracellular environment with injection of lentivirus-mediated transfection of chondroitinase ABC gene at the rostral and caudal borders of the lesion site and simultaneously leveraging the repair capacity of transplanted Schwann cells in adult rats following a mid-thoracic contusive spinal cord *** report that when the glial scar was degraded by chondroitinase ABC at the rostral and caudal lesion borders,Schwann cells migrated for considerable distances in both rostral and caudal *** Schwann cell migration led to enhanced axonal regrowth,including the serotonergic and dopaminergic axons originating from supraspinal regions,and promoted recovery of locomotor and urinary bladder ***,the Schwann cell survival and axonal regrowth persisted up to 6 months after the injury,even when treatment was delayed for 3 months to mimic chronic spinal cord *** findings collectively show promising evidence for a combinatorial strategy with chondroitinase ABC and Schwann cells in promoting remodeling and recovery of function following spinal cord injury.

关键词： axonal regrowth bladder function chondroitinase ABC functional recovery glial scar lentivirus migration Schwann cell spinal cord injury transplantation

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Impacts of Nutlin-3a and exercise on murine double minute 2-enriched glioma treatment

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Neural Regeneration Research 2025年第4期20卷 1135-1152页

作者： Yisheng Chen Zhongcheng Fan Zhiwen Luo Xueran Kang Renwen Wan Fangqi Li Weiwei Lin Zhihua Han Beijie Qi Jinrong Lin Yaying Sun Jiebin Huang Yuzhen Xu Shiyi Chen Department of Sport Medicine Huashan HospitalFudan UniversityShanghaiChina Department of Orthopedic surgery Hainan Province Clinical Medical CenterHaikou Affiliated Hospital of Central South University Xiangya School of MedicineHaikouHainan ProvinceChina Department of Basic Medicine Shanghai Jiao Tong University School of MedicineShanghai Jiao Tong UniversityShanghaiChina Department of Neurosurgery Second Affiliated Hospital of Zhejiang University School of MedicineZhejiang UniversityHangzhouZhejiang ProvinceChina Department of Orthopedics Shanghai General HospitalSchool of Medicine Shanghai Jiao Tong UniversityShanghaiChina Department of Infectious Diseases Children’s Hospital of Fudan UniversityNational Children’s Medical CenterShanghaiChina Department of Rehabilitation The Second Affiliated Hospital of Shandong First Medical UniversityTaianShandong ProvinceChina

Recent research has demonstrated the impact of physical activity on the prognosis of glioma patients,with evidence suggesting exercise may reduce mortality risks and aid neural *** role of the small ubiquitin-like modifier(SUMO)protein,especially post-exercise,in cancer progression,is gaining attention,as are the potential anti-cancer effects of *** used machine learning to create the exercise and SUMO-related gene signature(ESLRS).This signature shows how physical activity might help improve the outlook for low-grade glioma and other *** demonstrated the prognostic and immunotherapeutic significance of ESLRS markers,specifically highlighting how murine double minute 2(MDM2),a component of the ESLRS,can be targeted by *** underscores the intricate relationship between natural compounds such as nutlin-3 and immune *** comprehensive CRISPR screening,we validated the effects of specific ESLRS genes on low-grade glioma *** also revealed insights into the effectiveness of Nutlin-3a as a potent MDM2 inhibitor through molecular docking and dynamic ***-3a inhibited glioma cell proliferation and activated the p53 *** efficacy decreased with MDM2 overexpression,and this was reversed by Nutlin-3a or *** using a low-grade glioma mouse model highlighted the effect of physical activity on oxidative stress and molecular pathway ***,both physical exercise and Nutlin-3a administration improved physical function in mice bearing tumors derived from MDM2-overexpressing *** results suggest the potential for Nutlin-3a,an MDM2 inhibitor,with physical exercise as a therapeutic approach for glioma *** research also supports the use of natural products for therapy and sheds light on the interaction of exercise,natural products,and immune regulation in cancer treatment.

关键词： exercise and SUMO-related gene signatures(ESLRS) glioblastoma management low-grade glioma natural bioactives neural regeneration physical exercise

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Autophagy-targeting modulation to promote peripheral nerve regeneration

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Neural Regeneration Research 2025年第7期20卷 1864-1882页

作者： Yan Chen Hongxia Deng Nannan Zhang Department of Obstetrics and Gynecology West China Second HospitalSichuan UniversityChengduSichuan ProvinceChina Key Laboratory of Birth Defects and Women and Children’s Diseases Ministry of EducationSichuan UniversityChengduSichuan ProvinceChina Laboratory of Reproductive Endocrinology and Reproductive Regulation Sichuan UniversityChengduSichuan ProvinceChina National center for Birth Defect Monitoring West China Second University HospitalSichuan UniversityChengduSichuan ProvinceChina

Nerve regeneration following traumatic peripheral nerve injuries and neuropathies is a complex process modulated by diverse factors and intricate molecular *** studies have focused on factors that stimulate axonal outgrowth and myelin ***,recent studies have highlighted the pivotal role of autophagy in peripheral nerve regeneration,particularly in the context of traumatic ***,autophagy-targeting modulation has emerged as a promising therapeutic approach to enhancing peripheral nerve *** current understanding suggests that activating autophagy facilitates the rapid clearance of damaged axons and myelin sheaths,thereby enhancing neuronal survival and mitigating injury-induced oxidative stress and *** actions collectively contribute to creating a favorable microenvironment for structural and functional nerve regeneration.A range of autophagyinducing drugs and interventions have demonstrated beneficial effects in alleviating peripheral neuropathy and promoting nerve regeneration in preclinical models of traumatic peripheral nerve *** review delves into the regulation of autophagy in cell types involved in peripheral nerve regeneration,summarizing the potential drugs and interventions that can be harnessed to promote this *** hope that our review will offer novel insights and perspectives on the exploitation of autophagy pathways in the treatment of peripheral nerve injuries and neuropathies.

关键词： autophagy autophagy related genes Charcot–Marie–Tooth diseases diabetic peripheral neuropathy metformin myelination peripheral nerve injury Schwann cells sciatic nerve Wallerian degeneration

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Hsa-miR-214-3p inhibits breast cancer cell growth and improves the tumor immune microenvironment by downregulating B7H3

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Oncology research 2025年第1期33卷 103-121页

作者： Yan Lu Kang Wang Yuanhong Peng Meng Chen Lin Zhong Luji Huang F U Cheng Xindan Sheng Xin Yang Manzhao Ouyang George A Calin Zhiwei He China-America Cancer Research Institute Guangdong Medical University Dongguan 523808 China. GCP center Shunde Hospital Southern Medical University (The First People's Hospital of Shunde Foshan) Shunde 528300 China. Department of Gastrointestinal surgery Shunde Hospital Southern Medical University (The First People's Hospital of Shunde Foshan) Shunde 528300 China. The second School of Clinical Medicine Southern Medical University Guangzhou 510080 China. Department of Translational Molecular Pathology The University of Texas MD Anderson Cancer Center Houston TX 77030 USA. Department of Oncology Shunde Hospital Southern Medical University (The First People's Hospital of Shunde Foshan) Shunde 528300 China.

Background:Immune checkpoint inhibitors play an important role in the treatment of solid tumors, but the currently used immune checkpoint inhibitors targeting programmed cell death-1 (PD-1), programmed cell death ligand-1 (PD-L1), and cytotoxic T-lymphocyte antigen-4 (CTLA-4) show limited clinical efficacy in many breast cancers. B7H3 has been widely reported as an immunosuppressive molecule, but its immunological function in breast cancer patients remains unclear.Methods:We analyzed the expression of B7H3 in breast cancer samples using data from the Cancer Genome Atlas Program (TCGA) and the Gene Expression Omnibus (GEO) databases. MicroRNAs were selected using the TarBase, miRTarBase, and miRBase databases. The regulatory role of the microRNA hsa-miR-214-3p on B7H3 was investigated through dual-luciferase reporter assays, which identified the specific action sites of interaction. The expression levels of B7H3 and hsa-miR-214-3p in human breast cancer tissues and adjacent normal tissues were quantified using Western blotting and quantitative PCR (qPCR). experiments were performed to observe the effects of modulating the expression of B7H3 or hsa-miR-214-3p on breast cancer cell proliferation and apoptosis. Additionally, the regulatory impact of hsa-miR-214-3p on B7H3 was examined. Enzyme-linked immunosorbent assays (ELISA) and flow cytometry were employed to assess the effects of co-cultured breast cancer cells and normal human peripheral blood mononuclear cells (PBMCs) on immune cells and associated cytokines.Results:In breast cancer tissues, the expression level of B7H3 is inversely correlated with that of hsa-miR-214-3p, as well as with the regulatory effects on breast cancercell behavior. Hsa-miR-214-3p was found to inhibit breast cancer cell growth by downregulating B7H3. Importantly, our research identified, for the first time, two binding sites for hsa-miR-214-3p on the 3' UTR of B7H3, both of which exert similar effects independently. Co-culture experime

关键词： B7H3 Breast cancer Hsa-miR-214-3p Immunotherapy

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Polymorphism of heat shock protein 70-2 and enterocutaneous fistula in Chinese population

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World Journal of Gastroenterology 2014年第35期20卷 12559-12565页

作者： Jun Chen Jian-An Ren Gang Han Guo-Sheng Gu Ge-Fei Wang Xiu-Wen Wu Bo Zhou Dong Hu Yin Wu Yun-Zhao Zhao Jie-Shou Li Department of surgery the Research Institute of General SurgeryJinling Hospital general surgery center of the second hospital of jilin university Department of surgery The Research Institute of General SurgeryJinling Hospital Medical School of Nanjing university

AIM: To investigate whether the heat shock protein 70-2 (HSP70-2) polymorphism is associated with enterocutaneous fistulas in a Chinese population.

关键词： Enterocutaneous fistulas Single nucleotide polymorphisms Heat shock protein HSP70-2

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Conditional survival probability of distant-metastatic hepatocellular carcinoma: A population-based study

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World Journal of Gastrointestinal Oncology 2023年第11期15卷 1874-1890页

作者： Yong-Ping Yang Cheng-Jun Guo Zhao-Xuan Gu Jun-Jie Hua Jia-Xuan Zhang Jian Shi Department of general surgery The Second Hospital of Jilin UniversityChangchun 130041Jilin ProvinceChina

BACKGROUND The prognosis of many patients with distant metastatic hepatocellular carcinoma(HCC)improved after they survived for several *** with tradi-tional survival analysis,conditional survival(CS)which takes into account changes in survival risk could be used to describe dynamic survival *** To evaluate CS of distant metastatic HCC *** Patients diagnosed with distant metastatic HCC between 2010 and 2015 were extracted from the Surveillance,Epidemiology and End Results *** and multivariate Cox regression analysis were used to identify factors for overall survival(OS),while competing risk model was used to identify risk factors for cancer-specific survival(CSS).Six-month CS was used to calculate the probability of survival for an additional 6 mo at a specific time after initial diagnosis,and standardized difference(d)was used to evaluate the survival differences between *** were constructed to predict ***α-fetoprotein expression,higher T stage(T3 and T4),N1 stage,non-primary site surgery,non-chemotherapy,non-radiotherapy,and lung metastasis were independent risk factors for actual OS and CSS through univariate and multivariate *** survival rates decreased over time,while CS rates gradually *** for the 6-month CS,the survival difference caused by chemotherapy and radiotherapy gradually disappeared over time,and the survival difference caused by lung metastasis ***,the influence of age and gender on survival gradually *** were fitted for patients who have lived for 2,4 and 6 mo to predict 6-month conditional OS and CSS,*** area under the curve(AUC)of nomograms for conditional OS decreased as time passed,and the AUC for conditional CSS gradually *** CS for distant metastatic HCC patients substantially increased over *** dynamic risk factors,nomograms constructed at a specific time could predict more accur

关键词： Conditional survival Hepatocellular carcinoma Distant metastasis Prognosis Nomogram

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Ductal breast carcinoma metastasized to the rectum: A case report and review of the literature

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World Journal of Clinical Cases 2021年第36期9卷 11346-11354页

作者： Bo Ban Kai Zhang Jian-Nan Li Tong-Jun Liu Jian Shi Department of general surgery The Second Hospital of Jilin UniversityChangchun 130041Jilin ProvinceChina

BACKGROUND Gastrointestinal(GI)metastasis from breast cancer(BC)is rarely encountered in clinical *** symptoms and long intervals make early diagnosis ***,increased awareness of GI metastasis secondary to BC and a deep understanding of the clinical and pathological features,and intervention for GI metastasis are fundamental to avoid delay in correct diagnosis and *** SUMMARY The present report discusses the case of a Chinese female patient aged 36 *** patient presented with difficult defecation along with bloody stools and *** 2015,she had undergone right modified radical mastectomy and axillary lymph node dissection in another hospital to treat the infiltrating ductal breast carcinoma *** presenting symptoms were investigated by colonoscopy,which indicated a circumferential stricture in the lower rectum at 3 cm from the anal *** investigation with positron emission tomography-computed tomography revealed an uptake of fluorodeoxyglucose within the distal rectum as well as in the left *** samples from laparoscopic exploration were biopsied,which revealed metastases of *** analysis of the tumor confirmed that the patient had rectal metastasis of infiltrating ductal *** Rectal metastasis should be considered when patients with a history of BC present with changed bowel habits.

关键词： Breast cancer Ductal carcinoma Rectal metastases Case report

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Development and validation of a nomogram for predicting metachronous peritoneal metastasis in colorectal cancer:A retrospective study

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World Journal of Gastrointestinal Oncology 2023年第1期15卷 112-127页

作者： Bo Ban An Shang Jian Shi Department of general surgery The Second Hospital of Jilin UniversityChangchun 130041Jilin ProvinceChina

BACKGROUND Peritoneal metastasis(PM)after primary surgery for colorectal cancer(CRC)has the worst *** and early detection of metachronous PM(m-PM)have an important role in improving postoperative prognosis of ***,commonly used imaging methods have limited sensitivity to detect PM *** aimed to establish a nomogram model to evaluate the individual probability of m-PM to facilitate early interventions for high-risk *** To establish and validate a nomogram model for predicting the occurrence of m-PM in CRC within 3 years after *** We used the clinical data of 878 patients at the second hospital of jilin university,between January 1,2014 and January 31,*** patients were randomly divided into training and validation cohorts at a ratio of 2:*** least absolute shrinkage and selection operator(LASSO)regression was performed to identify the variables with nonzero coefficients to predict the risk of *** logistic regression was used to verify the selected variables and to develop the predictive nomogram ***’s concordance index,receiver operating characteristic curve,Brier score,and decision curve analysis(DCA)were used to evaluate discrimination,distinctiveness,validity,and clinical utility of this nomogram *** model was verified internally using bootstrapping method and verified externally using validation *** LASSO regression analysis identified six potential risk factors with nonzero *** logistic regression confirmed the risk factors to be *** on the results of two regression analyses,a nomogram model was *** nomogram included six predictors:Tumor site,histological type,pathological T stage,carbohydrate antigen 125,v-raf murine sarcoma viral oncogene homolog B mutation and microsatellite instability *** model achieved good predictive accuracy on both the training and validation *** C-index,area under the curve,and

关键词： Colorectal cancer Metachronous peritoneal metastasis Risk factor Nomogram

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Melatonin combined with chondroitin sulfate ABC promotes nerve regeneration after root-avulsion brachial plexus injury

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Neural Regeneration Research 2019年第2期14卷 328-338页

作者： Wen-Lai Guo Zhi-Ping Qi Li Yu Tian-Wen Sun Wen-Rui Qu Qian-Qian Liu Zhe Zhu Rui Li Department of Hand surgery the Second Hospital of Jilin University Department of Orthopedics the Second Hospital of Jilin University Department of Ophthalmology the Second Hospital of Jilin University Department of Orthopedics China-Japan Union Hospital of Jilin University

After nerve-root avulsion injury of the brachial plexus, oxidative damage, inflammatory reaction, and glial scar formation can affect nerve regeneration and functional recovery. Melatonin(MT) has been shown to have good anti-inflammatory, antioxidant, and neuroprotective effects. Chondroitin sulfate ABC(ChABC) has been shown to metabolize chondroitin sulfate proteoglycans and can reduce colloidal scar formation. However, the effect of any of these drugs alone in the recovery of nerve function after injury is not completely satisfactory. Therefore, this experiment aimed to explore the effect and mechanism of combined application of melatonin and chondroitin sulfate ABC on nerve regeneration and functional recovery after nerve-root avulsion of the brachial plexus. Fifty-two Sprague-Dawley rats were selected and their C5–7 nerve roots were avulsed. Then, the C6 nerve roots were replanted to construct the brachial plexus nerve-root avulsion model. After successful modeling, the injured rats were randomly divided into four groups. The first group(injury) did not receive any drug treatment, but was treated with a pure gel-sponge carrier nerve-root implantation and an ethanol-saline solution via intraperitoneal(i.p.) injection. The second group(melatonin) was treated with melatonin via i.p. injection. The third group(chondroitin sulfate ABC) was treated with chondroitin sulfate ABC through local administration. The fourth group(melatonin + chondroitin sulfate ABC) was treated with melatonin through i.p. injection and chondroitin sulfate ABC through local administration. The upper limb Terzis grooming test was used 2–6 weeks after injury to evaluate motor function. Inflammation and oxidative damage within 24 hours of injury were evaluated by spectrophotometry. Immunofluorescence and neuroelectrophysiology were used to evaluate glial scar, neuronal protection, and nerve regeneration. The results showed that the Terzis grooming-test scores of the three groups that received tr

关键词： nerve regeneration nerve injury transitional zone chondroitin sulfate proteoglycan astrocyte motor neuron oxidative damage inflammatory response glial scar

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Development of artificial intelligence technology in diagnosis,treatment,and prognosis of colorectal cancer

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World Journal of Gastrointestinal Oncology 2022年第1期14卷 124-152页

作者： Feng Liang Shu Wang Kai Zhang Tong-Jun Liu Jian-Nan Li Department of general surgery The Second Hospital of Jilin UniversityChangchun 130041Jilin ProvinceChina Department of Radiotherapy Jilin University Second HospitalChangchun 130041Jilin ProvinceChina

Artificial intelligence(AI)technology has made leaps and bounds since its *** technology can be subdivided into many technologies such as machine learning and deep *** application scope and prospect of different technologies are also totally ***,AI technologies play a pivotal role in the highly complex and wide-ranging medical field,such as medical image recognition,biotechnology,auxiliary diagnosis,drug research and development,and *** cancer(CRC)is a common gastrointestinal cancer that has a high mortality,posing a serious threat to human *** CRCs are caused by the malignant transformation of colorectal ***,early diagnosis and treatment are crucial to CRC *** methods of diagnosing CRC are divided into imaging diagnosis,endoscopy,and pathology *** methods are divided into endoscopic treatment,surgical treatment,and drug *** technology is in the weak era and does not have communication ***,the current AI technology is mainly used for image recognition and auxiliary analysis without in-depth communication with *** article reviews the application of AI in the diagnosis,treatment,and prognosis of CRC and provides the prospects for the broader application of AI in CRC.

关键词： Artificial intelligence Colorectal cancer Diagnosis Treatment Prognosis

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