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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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Enhancing m^(6)A modification in the motor cortex facilitates corticospinal tract remodeling after spinal cord injury

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Neural Regeneration research 2025年第6期20卷 1749-1763页

作者： Tian Qin Yuxin Jin Yiming Qin Feifei Yuan Hongbin Lu Jianzhong Hu Yong Cao Chengjun Li Department of Spine surgery and Orthopedics Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina Key Laboratory of Organ Injury Aging and Regenerative Medicine of Hunan ProvinceChangshaHunan ProvinceChina National clinical research center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina Department of Sports Medicine Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina

Spinal cord injury typically causes corticospinal tract disruption. Although the disrupted corticospinal tract can self-regenerate to a certain degree, the underlying mechanism of this process is still unclear. N6-methyladenosine(m^(6)A) modifications are the most common form of epigenetic regulation at the RNA level and play an essential role in biological processes. However, whether m^(6)A modifications participate in corticospinal tract regeneration after spinal cord injury remains unknown. We found that expression of methyltransferase 14 protein(METTL14) in the locomotor cortex was high after spinal cord injury and accompanied by elevated m^(6)A levels. Knockdown of Mettl14 in the locomotor cortex was not favorable for corticospinal tract regeneration and neurological recovery after spinal cord injury. Through bioinformatics analysis and methylated RNA immunoprecipitation-quantitative polymerase chain reaction, we found that METTL14 regulated Trib2 expression in an m^(6)A-regulated manner, thereby activating the mitogen-activated protein kinase pathway and promoting corticospinal tract regeneration. Finally, we administered syringin, a stabilizer of METTL14, using molecular docking. Results confirmed that syringin can promote corticospinal tract regeneration and facilitate neurological recovery by stabilizing METTL14. Findings from this study reveal that m^(6)A modification is involved in the regulation of corticospinal tract regeneration after spinal cord injury.

关键词： corticospinal tract remodeling epigenetic regulations locomotor cortex m^(6)A modification methyltransferase 14 protein(METTL14) mitogen-activated protein kinase neural regeneration spinal cord injury syringin TRIB2

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Prognostic utility of gamma-glutamyl transpeptidase to platelet ratio in patients with solitary hepatitis B virus-related hepatocellular carcinoma after hepatectomy

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World Journal of Gastrointestinal Oncology 2024年第12期16卷 4579-4596页

作者： Cheng-Kun Yang Zhong-Liu Wei Xiao-Qiang Shen Yu-Xuan Jia Qiong-Yuan Wu Yong-Guang Wei Hao Su Wei Qin Xi-Wen Liao Guang-Zhi Zhu Tao Peng Department of Hepatobiliary surgery The First Affiliated Hospital of Guangxi Medical UniversityNanning 530021Guangxi Zhuang Autonomous RegionChina guangxi Key Laboratory of enhanced recovery after surgery for Gastrointestinal Cancer Nanning 530021Guangxi Zhuang Autonomous RegionChina Department of Tuina Nanning Hospital of Traditional Chinese MedicineNanning 530022Guangxi Zhuang Autonomous RegionChina

BACKGROUND The prognostic impact of preoperative gamma-glutamyl transpeptidase to platelet ratio(GPR)levels in patients with solitary hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC)following radical resection has not been *** To examine the clinical utility of GPR for prognosis prediction in solitary HBVrelated HCC *** A total of 1167 solitary HBV-related HCC patients were retrospectively *** levels were compared with 908 non-HCC *** survival(OS)and recurrence-free survival(RFS)were evaluated,and cox proportional hazard model analyses were performed to identify independent risk *** in characteristics were adjusted by propensity score matching(PSM).Subgroup and stratified survival analyses for HCC risks were performed,and a linear trend of the hazard ratio(HR)according to GPR levels was *** GPR levels of patients with solitary HBV-related HCC were higher than those with hepatic hemangiomas,chronic hepatitis B and healthy control(adjusted Pafter the PSM balance *** low GPR group had improved OS(P0.6 was associated with a worse OS and higher recurrence rate(P for trend<0.001).CONCLUSION Preoperative GPR can serve as a noninvasive indicator to predict the prognosis of patients with solitary HBVrelated HCC.

关键词： Gamma-glutamyl transpeptidase to platelet ratio Hepatitis B virus Hepatocellular carcinoma Prognosis Propensity score matching

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Change of tumor-infiltrating lymphocyte of associating liver partition and portal vein ligation for staged hepatectomy for hepatocellular carcinoma

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World Journal of Gastrointestinal surgery 2022年第9期14卷 1008-1025页

作者： Wei Wang Zhen-Feng Deng Ji-Long Wang Ling Zhang Li Bao Bang-Hao Xu Hai Zhu Ya Guo Zhang Wen Department of Hepatobiliary surgery The First Affiliated Hospital of Guangxi Medical UniversityNanning 530021Guangxi Zhuang Autonomous RegionChina guangxi Key Laboratory of enhanced recovery after surgery for Gastrointestinal Cancer The First Affiliated Hospital of Guangxi Medical UniversityNanning 530021Guangxi Zhuang Autonomous RegionChina Department of Radiology The First Affiliated Hospital of Guangxi Medical UniversityNanning 530021Guangxi Zhuang Autonomous RegionChina Key Laboratory of Cancer Prevention and Therapy Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerTianjin 300000China

BACKGROUND The role of tumor-infiltrating lymphocytes(TILs)in the growth and progression of hepatocellular carcinoma(HCC)has attracted widespread *** To evaluate the feasibility of associating liver partition and portal vein ligation for staged hepatectomy(ALPPS)for massive HCC by exploring the role of TIL in the tumor *** Fifteen massive HCC patients who underwent ALPPS treatment and 46 who underwent hemi-hepatectomy were selected for this *** score matching was utilized to match patients in ALPPS and hemi-hepatectomy groups(1:1).Quantitative analysis of TILs in tumor and adjacent tissues between the two groups was performed by immunofluorescence staining and further analyses with oncological *** the meantime,trends of TILs in peripheral blood RESULTS Continuous measurement of tumor volume and necrosis volume showed that the proportion of tumor necrosis volume on the seventh day after stage-I ALPPS was significantly higher than the pre-operative value(P=0.024).In the preoperative period of stage-I ALPPS,the proportion of tumor necrosis volume in the high CD8+T cell infiltration group was significantly higher than that in the low group(P=0.048).CONCLUSION TIL infiltration level maintained a dynamic balance during the preoperative period of *** with right hemi-hepatectomy,the ALPPS procedure does not cause severe immunosuppression with the decrease in TIL infiltration and pathological changes in immune components of peripheral *** results suggested that ALPPS is safe and feasible for treating massive HCC from the perspective of *** addition,high CD8+T cell infiltration is associated with increasing tumor necrosis in the perioperative period of ALPPS.

关键词： Associating liver partition and portal vein ligation for staged hepatectomy Tumor-infiltrating lymphocytes Multiplexed immunohistochemistry Tumor necrosis

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CD4^(+)CD25^(+) regulatory T cells decreased future liver remnant after associating liver partition and portal vein ligation for staged hepatectomy

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World Journal of Gastrointestinal surgery 2023年第5期15卷 917-930页

作者： Wei Wang Chun-Hui Ye Zhen-Feng Deng Ji-Long Wang Ling Zhang Li Bao Bang-Hao Xu Hai Zhu Ya Guo Zhang Wen Department of Hepatobiliary surgery The First Affiliated Hospital of Guangxi Medical UniversityNanning 530021Guangxi Zhuang Autonomous RegionChina guangxi Key Laboratory of enhanced recovery after surgery for Gastrointestinal Cancer The First Affiliated Hospital of Guangxi Medical UniversityNanning 530021Guangxi Zhuang Autonomous RegionChina Department of Radiology The First Affiliated Hospital of Guangxi Medical UniversityNanning 530021Guangxi Zhuang Autonomous RegionChina Key Laboratory of Cancer Prevention and Therapy Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerTianjin 300000China

BACKGROUND Associating liver partition and portal vein ligation for staged hepatectomy(ALPPS)is an innovative surgical approach for the treatment of massive hepatocellular carcinoma(HCC),the key to successful planned stage 2 ALPPS is future liver remnant(FLR)volume growth,but the exact mechanism has not been *** correlation between regulatory T cells(Tregs)and postoperative FLR regeneration has not been *** To investigate the effect of CD4^(+)CD25^(+)Tregs on FLR regeneration after *** clinical data and specimens were collected from 37 patients who developed massive HCC treated with *** cytometry was performed to detect changes in the proportion of CD4^(+)CD25^(+)Tregs to CD4^(+)T cells in peripheral blood before and after *** analyze the relationship between peripheral blood CD4^(+)CD25^(+)Treg proportion and clinicopathological information and liver *** The postoperative CD4^(+)CD25^(+)Treg proportion in stage 1 ALPPS was negatively correlated with the amount of proliferation volume,proliferation rate,and kinetic growth rate(KGR)of the FLR after stage 1 *** with low Treg proportion had significantly higher KGR than those with high Treg proportion(P=0.006);patients with high Treg proportion had more severe postoperative pathological liver fibrosis than those with low Treg proportion(P=0.043).The area under the receiver operating characteristic curve between the percentage of Tregs and proliferation volume,proliferation rate,and KGR were all greater than *** CD4^(+)CD25^(+)Tregs in the peripheral blood of patients with massive HCC at stage 1 ALPPS were negatively correlated with indicators of FLR regeneration after stage 1 ALPPS and may influence the degree of fibrosis in patients’*** percentage was highly accurate in predicting the FLR regeneration after stage 1 ALPPS.

关键词： Associating liver partition and portal vein ligation for staged hepatectomy Regulatory T cells Future liver remnant

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Nutritional therapy for gastroparesis

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Journal of Nutritional Oncology 2023年第1期8卷 25-30页

作者： Zhen Wang Qin-Zhou Song Jin-Xun Jiang Xiang-Hua Wu Jun-Qiang Chen Departmentof Gastrointestinal Surgry The First Aflated Hospital of Guangxi Medical UniversityNanningGuangxiChina guangxi Key Laboratory of enhanced recovery after surgery of Gastrointestinal Cancer NanningGuangxiChina

Gastroparesis is a common postoperative complication of abdominal surgery,mainly manifested by postprandial fullness,early satiety,nausea,vomiting,and *** should be addressed with a comprehensive treatment plan that includes nutritional therapy and medications such as metoclopramide,domperidone,cisapride,and antiemetic *** treatment,such as pyloroplasty or partial gastrectomy,should be considered if the conservative therapy is *** and parenteral nutrition therapy can promote the recovery of gastrointestinal function,maintain the mucosal integrity and immunity,and reduce ***,nutrition can play an important role in the treatment of gastroparesis.

关键词： Gastroparesis Nutritional therapy surgery

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Pharmacological targeting cGAS/STING/NF-κB axis by tryptanthrin induces microglia polarization toward M2 phenotype and promotes functional recovery in a mouse model of spinal cord injury

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Neural Regeneration research 2025年第11期20卷 3287-3301页

作者： Ziwei Fan Mengxian Jia Jian Zhou Zhoule Zhu Yumin Wu Xiaowu Lin Yiming Qian Jiashu Lian Xin Hua Jianhong Dong Zheyu Fang Yuqing Liu Sibing Chen Xiumin Xue Juanqing Yue Minyu Zhu Ying Wang Zhihui Huang Honglin Teng Department of Orthopedics(Spine surgery) the First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang ProvinceChina School of Pharmacy Hangzhou Normal UniversityHangzhouZhejiang ProvinceChina Department of Neurology The First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang ProvinceChina Department of Pathology Affiliated Hangzhou First People’s HospitalSchool of MedicineWestlake UniversityHangzhouZhejiang ProvinceChina Department of clinical research center Affiliated Hangzhou First People’s HospitalSchool of MedicineWestlake UniversityHangzhouZhejiang ProvinceChina

The M1/M2 phenotypic shift of microglia after spinal cord injury plays an important role in the regulation of neuroinflammation during the secondary injury phase of spinal cord *** of shifting microglia polarization from M1(neurotoxic and proinflammatory type)to M2(neuroprotective and anti-inflammatory type)after spinal cord injury appears to be *** possesses an anti-inflammatory biological ***,its roles and the underlying molecular mechanisms in spinal cord injury remain *** this study,we found that tryptanthrin inhibited microglia-derived inflammation by promoting polarization to the M2 phenotype in *** promoted M2 polarization through inactivating the cGAS/STING/NF-κB ***,we found that targeting the cGAS/STING/NF-κB pathway with tryptanthrin shifted microglia from the M1 to M2 phenotype after spinal cord injury,inhibited neuronal loss,and promoted tissue repair and functional recovery in a mouse model of spinal cord ***,using a conditional co-culture system,we found that microglia treated with tryptanthrin suppressed endoplasmic reticulum stress-related neuronal *** together,these results suggest that by targeting the cGAS/STING/NF-κB axis,tryptanthrin attenuates microglia-derived neuroinflammation and promotes functional recovery after spinal cord injury through shifting microglia polarization to the M2 phenotype.

关键词： cGAS/STING functional recovery microglia neuroinflammation neuroprotection nuclear factor-κB polarization spinal cord injury tryptanthrin

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Nanoparticles for the treatment of spinal cord injury

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Neural Regeneration research 2025年第6期20卷 1665-1680页

作者： Qiwei Yang Di Lu Jiuping Wu Fuming Liang Huayi Wang Junjie Yang Ganggang Zhang Chen Wang Yanlian Yang Ling Zhu Xinzhi Sun Department of Orthopedic surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina CAS Key Laboratory of Standardization and Measurement for Nanotechnology CAS Key Laboratory for Biomedical Effects of Nanomaterials and NanosafetyCAS Center for Excellence in NanoscienceNational Center for Nanoscience and TechnologyBeijingChina University of Chinese Academy of Sciences BeijingChina Department of Neurosurgery The First Affiliated Hospital of Chongqing Medical UniversityChongqingChina

Spinal cord injuries lead to significant loss of motor, sensory, and autonomic functions, presenting major challenges in neural regeneration. Achieving effective therapeutic concentrations at injury sites has been a slow process, partly due to the difficulty of delivering drugs effectively. Nanoparticles, with their targeted delivery capabilities, biocompatibility, and enhanced bioavailability over conventional drugs, are garnering attention for spinal cord injury treatment. This review explores the current mechanisms and shortcomings of existing treatments, highlighting the benefits and progress of nanoparticle-based approaches. We detail nanoparticle delivery methods for spinal cord injury, including local and intravenous injections, oral delivery, and biomaterial-assisted implantation, alongside strategies such as drug loading and surface modification. The discussion extends to how nanoparticles aid in reducing oxidative stress, dampening inflammation, fostering neural regeneration, and promoting angiogenesis. We summarize the use of various types of nanoparticles for treating spinal cord injuries, including metallic, polymeric, protein-based, inorganic non-metallic, and lipid nanoparticles. We also discuss the challenges faced, such as biosafety, effectiveness in humans, precise dosage control, standardization of production and characterization, immune responses, and targeted delivery in vivo. Additionally, we explore future directions, such as improving biosafety, standardizing manufacturing and characterization processes, and advancing human trials. Nanoparticles have shown considerable progress in targeted delivery and enhancing treatment efficacy for spinal cord injuries, presenting significant potential for clinical use and drug development.

关键词： antioxidants axon regeneration biocompatible materials drug carriers nanoparticles nerve regeneration neuroinflammatory diseases neuroprotection spinal cord injury stem cells

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Prognostic value of cachexia defined by the Asian Working Group for Cachexia criteria in patients with gastric cancer

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Journal of Nutritional Oncology 2024年第2期9卷 63-71,I0001页

作者： Hai-Lun Xie Li-Shuang Wei Shu-Yao Wang Chang-Hong Xu Guo-Tian Ruan He-Yang Zhang Han-Ping Shi Jun-Qiang Chen Department of Gastrointestinal Gland surgery The First Affiliated Hospital of Guangxi Medical UniversityNanning 530021GuangxiChina Department of General surgery Beijing Friendship HospitalCapital Medical UniversityBeijing 100050China Department of Gastroenterology Beijing Friendship HospitalCapital Medical UniversityBeijing 100050China center of Cancer Nutrition and Metabolism Beijing Shijitan HospitalCapital Medical UniversityBeijing 100038China guangxi Key Laboratory of enhanced recovery after surgery for Gastrointestinal Cancer The First Affiliated Hospital of Guangxi Medical UniversityNanning 530021GuangxiChina guangxi clinical research center for enhanced recovery after surgery The First Affiliated Hospital of GuangxiMedical UniversityNanning 530021GuangxiChina and 7guangxi Zhuang Autonomous Region Engineering research center for Artificial Intelligence Analysis of Multimodal Tumor Images The First Affiliated Hospital of Guangxi Medical UniversityNanning 530021GuangxiChina

Background:The Asian Working Group for Cachexia(AWGC)criteria are newly proposed diagnostic standards specifically designed for Asian *** research focused on validating the predictive value of the AWGC criteria for assessing the prognosis and medical burden of patients with gastric ***:Cox proportional hazards analysis was conducted to evaluate the association between cachexia and overall *** regression analysis was used to assess whether there was an independent association between cachexia and the 90-day mortality,the length of stay and the quality of ***’s concordance index was utilized to demonstrate the discriminative ability of different diagnostic criteria for ***:AWGC-defined cachexia was an independent risk factor for a reduced overall survival in patients(HR=1.397,95%CI=1.209–1.615,Pclinical benefit(0.029,95%CI=0.048–0.008,P=0.005).Logistic regression analysis showed that only AWGC-defined cachexia was an independent risk factor for 90-day mortality(OR=2.142,95%CI=1.397–3.282,P<0.001)and prolonged hospitalization(OR=1.958,95%CI=1.587–2.416,P<0.001)in patients with gastric cancer,whereas cachexia defined by the Fearon criteria was *** with AWGC-defined cachexia exhibited significant reductions in physical function,role function,emotional function,cognitive function,social functioning,and overall quality-of-life ***,cachectic patients showed higher levels of fatigue,nausea and vomiting,pain,dyspnea,sleep disturbance,appetite loss,constipation,and financial difficulties.A multivariate logistic regression showed that patients with AWGC-defined cachexia had a 126.1%increased risk of impaired quality of life(OR=2.261,95%CI=1.859–2.749,P<0.001).Conclusions:The AWGC criteria are an

关键词： Cachexia AWGC criteria Survival 90-Day mortality Gastric cancer

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Upregulation of epidermal growth factor receptor 4 in oral leukoplakia

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International Journal of Oral Science 2013年第1期5卷 14-20页

作者： Hiroshi Kobayashi Kenichi Kumagai Akito Gotoh Takanori Eguchi Hiroyuki Yamada Yoshiki Hamada Satsuki Suzuki Ryuji Suzuki Department of Oral and Maxillofacial surgery Tsurumi University Department of Rheumatology and clinical Immunology Clinical Research Center for Rheumatology and AllergySagamihara National HospitalNational Hospital Organization Section of Biological Science research center for Odontology Nippon Dental University School of Dentistry

In the present study,we investigate the expression profile of the epidermal growth factor receptor family,which comprises EGFR/ ErbBl,HER2/ErbB2,HER3/ErbB3 and HER4/ErbB4 in oral leukoplakia(LP).The expression of four epidermal growth factor receptor (EGFR) family genes and their ligands were measured in LP tissues from 14 patients and compared with levels in 10 patients with oral lichen planus(OLP) and normal oral mucosa(NOM) from 14 healthy donors by real-time polymerase chain reaction(PCR) and *** mRNA coexpression of ErbBl,ErbB2,ErbB3and ErbB4 was detected in LP *** of the receptors,only ErbB4 mRNA and protein was more highly expressed in LP compared with NOM *** were strongly expressed by epithelial keratinocytes in LP lesions,as shown by *** the ligands,the mRNA of Neuregulin2 and 4 were more highly expressed in OLP compared with NOM ***,enhanced ErbB4 on the keratinocytes and synchronous modulation of EGFR family genes may contribute to the pathogenesis and carcinogenesis of LP.

关键词： epidermal growth factor receptor immunohistochemistry oral leukoplakia quantitative real-time polymerase chain reaction

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