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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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Repetitive transcranial magnetic stimulation in Alzheimer’s disease:effects on neural and synaptic rehabilitation

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Neural Regeneration Research 2025年第2期20卷 326-342页

作者： Yi Ji Chaoyi Yang Xuerui Pang Yibing Yan Yue Wu Zhi Geng Wenjie Hu Panpan Hu Xingqi Wu Kai Wang Department of Neurology The First Affiliated Hospital of Anhui Medical UniversityHefeiAnhui ProvinceChina anhui Province Key Laboratory of Cognition and Neuropsychiatric Disorders HefeiAnhui ProvinceChina Collaborative Innovation Center of Neuropsychiatric Disorders and Mental Health HefeiAnhui ProvinceChina Institute of Artificial Intelligence Hefei Comprehensive National Science CenterHefeiAnhui ProvinceChina Department of Psychology and Sleep Medicine The Second Affiliated Hospital of Anhui Medical UniversityHefeiAnhui ProvinceChina

Alzheimer’s disease is a neurodegenerative disease resulting from deficits in synaptic transmission and *** Alzheimer’s disease brain tends to be hyperexcitable and hypersynchronized,thereby causing neurodegeneration and ultimately disrupting the operational abilities in daily life,leaving patients *** transcranial magnetic stimulation is a cost-effective,neuro-modulatory technique used for multiple neurological *** the past two decades,it has been widely used to predict cognitive decline;identify pathophysiological markers;promote neuroplasticity;and assess brain excitability,plasticity,and *** has also been applied to patients with dementia,because it can yield facilitatory effects on cognition and promote brain recovery after a neurological ***,its therapeutic effectiveness at the molecular and synaptic levels has not been elucidated because of a limited number of *** study aimed to characterize the neurobiological changes following repetitive transcranial magnetic stimulation treatment,evaluate its effects on synaptic plasticity,and identify the associated *** review essentially focuses on changes in the pathology,amyloidogenesis,and clearance pathways,given that amyloid deposition is a major hypothesis in the pathogenesis of Alzheimer’s *** mechanisms associated with repetitive transcranial magnetic stimulation procedures and different pathways mediating gene transcription,which are closely related to the neural regeneration process,are also ***,we discuss the outcomes of animal studies in which neuroplasticity is modulated and assessed at the structural and functional levels by using repetitive transcranial magnetic stimulation,with the aim to highlight future directions for better clinical translations.

关键词： Alzheimer’s disease amyloid deposition apoptotic mechanisms biomarker neural regeneration neurodegeneration repetitive transcranial magnetic stimulation synaptic plasticity

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Pulp health and calcific healing of a complicated crown–root fracture with additional root fracture in a maxillary incisor: A case report

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World Journal of Clinical Cases 2025年第3期13卷 42-49页

作者： Na Li Yue-Yue Ren Ying Tang Qi Yang Tian-Tian Meng Song Li Jing Zhang Stomatological hospital and College Anhui Medical UniversityHefei 230032Anhui ProvinceChina Department of Endodontics The Affiliated Stomatological Hospital of Xuzhou Medical UniversityXuzhou 221000Jiangsu ProvinceChina

BACKGROUND Complicated crown–root fracture (CRF) involves severe injury to the crown, root,and pulp, and may be accompanied by multiple root fractures. The loss of a toothhas lifelong consequences for children and teenagers, but the maintenance of pulphealth and the calcific healing of multiple root fractures are rarely reported in *** SUMMARY This case reports healing of a permanent tooth with complicated crown–root andadditional root fractures, in which pulp health was maintained. A 10-year-old girlfell and fractured the root of her maxillary left central incisor at the cervical *** the coronal fragment was repositioned, the tooth was splinted until thetooth was no longer mobile, 2 years later. Eight years after treatment, the toothhas remained asymptomatic with vital pulp and localized gingival ***-beam computed tomography revealed not only calcified healing of the CRFbut also spontaneous healing in an additional undiagnosed root fracture. Thefracture line on the enamel could not be healed by hard tissue and formed agroove in the cervical crown. It was speculated that the groove was related to thelocalized gingival *** This case provides a clinical perspective of the treatment of a tooth with acomplicated CRF and an additional root fracture.

关键词： Complicated crown-root fracture Multiple root fracture Spontaneous healing Cone-beam computed tomography Long-term follow-up Case report

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Peri-centrosomal localization of small interfering RNAs in C. elegans

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Science China Life Sciences 2025年

作者： Qile Jin Xuezhu Feng Minjie Hong Ke Wang Xiangyang Chen Jiewei Cheng Yan Kuang Xiaoyue Si Mingjing Xu Xinya Huang Shouhong Guang Chengming Zhu Department of Obstetrics and Gynecology The First Affiliated Hospital of USTC The USTC RNA Institute Hefei National Research Center for Physical Sciences at the Microscale School of Life Sciences Division of Life Sciences and Medicine Biomedical Sciences and Health Laboratory of Anhui Province University of Science and Technology of China School of Basic Medicine Anhui Medical University

The centrosome is the microtubule-organizing center and a crucial part of cell division. Centrosomal RNAs(cnRNAs) have been reported to enable precise spatiotemporal control of gene expression during cell division in many species. Whether and how cnRNAs exist in C. elegans are unclear. Here, using the nuclear RNAi Argonaute protein NRDE-3 as a reporter, we observed potential peri-centrosome localized small interfering(si)RNAs in C. elegans. NRDE-3 was previously shown to associate with pre-mRNAs and pre-rRNAs via a process involving the presence of complementary siRNAs. We generated a GFP-NRDE-3 knock-in transgene through CRISPR/Cas9 technology and observed that NRDE-3 formed peri-centrosomal foci neighboring the tubulin protein TBB-2, other centriole proteins and pericentriolar material(PCM)components in C. elegans embryos. The peri-centrosomal accumulation of NRDE-3 depends on RNA-dependent RNA polymerase(RdRP)-synthesized 22G siRNAs and the PAZ domain of NRDE-3, which is essential for siRNA binding. Mutation of eri-1, ergo-1, or drh-3 significantly increased the percentage of pericentrosome-enriched NRDE-3. At the metaphase of the cell cycle, NRDE-3 was enriched in both the peri-centrosomal region and the spindle. Moreover, the integrity of centriole proteins and pericentriolar material(PCM) components is also required for the peri-centrosomal accumulation of NRDE-3. Therefore, we concluded that siRNAs could accumulate in the pericentrosomal region in C. elegans and suggested that the peri-centrosomal region may also be a platform for RNAi-mediated gene regulation.

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A network pharmacology-based strategy for predicting the protect-ive mechanism of Ginkgo biloba on damaged retinal ganglion cells

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Chinese Journal of Natural Medicines 2022年第1期20卷 54-66页

作者： YU Hua DONG Li-Hong ZHANG Yan LIU Qiang chaohu hospital affiliated to anhui medical university Hefei 230000China

Hallmarks of the pathophysiology of glaucoma are oxidative stress and apoptotic death of retinal ganglion cells(RGCs).Ginkgo biloba extract(EGb)with multi-target,multi-pathway functions has been reported to exert positive pharmacological effects on oxidative stress and damaged ***,the ingredients and anti-apoptotic targets of EGb in the treatment of open-angle glaucoma(OAG)have not been fully ***,in-depth analysis is necessary for further *** biloba-re-lated and anti-apoptotic targets were identified and then combined to obtain the intersection,representing the potential anti-apoptotic targets of Ginkgo *** addition,compound-anti-apoptotic target and OAG-target protein-protein interaction network were merged to obtain five core genes and compound-OAG-anti-apoptotic target protein-protein interaction ***,the active com-pounds and anti-apoptotic targets of Ginkgo biloba in the treatment of OAG were identified,namely luteolin,β-sitosterol,kaempferol,stigmasterol,quercetin,and p53,Bax,Bcl-2,Caspase-3 and Caspase-9,*** the anti-apoptotic targets of Ginkgo biloba in the treatment of OAG,Gene Ontology(GO)and pathway analysis were executed to confirm the gene functions of Ginkgo biloba in antagonizing apoptosis of *** pathway enrichment was mainly involved in transcriptional activation of p53 responsive genes,activation of caspases and apoptotic ***,we confirmed the results of the network analysis by H2O2 treated RGC-5 cells in *** results demonstrated that EGb protection can effectively diminish H2O2-induced apoptosis by inhibiting p53 acetylation,reducing the ratio of Bax/Bcl-2 and suppressing the expression of specific cleavage of Caspase-9 and Caspase-3.

关键词： Ginkgo biloba Oxidative stress Retinal ganglion cells Apoptosis p53 Acetylation

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Long noncoding RNA LINC01106 promotes lung adenocarcinoma progression via upregulation of autophagy

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Oncology research 2025年第1期33卷 171-184页

作者： Gengyun Sun Yiping Zheng Jianfeng Cai Jie Gao Lie Dong Xiangbin Zhang Yinghui Huang Department of Respiratory and Critical Care Medicine The First Affiliated Hospital of Anhui Medical University Hefei 230022 China. Department of Respiratory and Critical Care Medicine Nanping First Hospital Affiliated to Fujian Medical University Nanping 353006 China.

Background:Long noncoding RNA, LINC01106 exhibits high expression in lung adenocarcinoma (LUAD) tumor tissues, but its functional role and regulatory mechanism in LUAD cells remain unclear.Methods:LINC01106 expression was analyzed in LUAD tissues and its functional impact on LUAD cells was assessed. LUAD cells were silenced with sh-LINC01106 and injected into nude mice to investigate tumor growth. The downstream transcription factors and molecular mechanism were determined using the Human transcription factor database (TFDB) database and Gene Expression Profiling Interactive Analysis (GEPIA) database. Additionally, the impact of linc01106 on autophagy was analyzed by determining the expression of autophagy-related genes (ATGs) in LUAD cells.Results:Our results showed that LINC01106 exhibited upregulation in both LUAD tissues and cell lines. The silencing of LINC01106 demonstrated a suppressive effect on tumorigenesis in a xenograft mouse model of LUAD. Additionally, LINC01106 was found to recruit TATA-binding protein-associated factor 15 (TAF15), an RNA-binding protein, thereby enhancing the mRNA stability of TEA domain transcription factor 4 (TEAD4). In turn, TEAD4 served as a transcription factor that bound to the LINC01106 promoter and regulated its expression. Further assays indicated that LINC01106 promoted autophagy in LUAD cells by upregulating the expression of autophagy-related genes (ATGs). The silencing of LINC01106 in LUAD cells inhibited autophagy, and cell proliferation, and promoted apoptosis, which all were effectively reversed by ATG5 overexpression.Conclusions:Overall, LINC01106, transcriptionally activated by TEAD4, interacts with TAF15 to promote the stability of TEAD4 and upregulates the expression of ATGs, promoting malignancy of LUAD cells.

关键词： ATG5 LINC01106 Lung adenocarcinoma (LUAD) Non-small cell lung cancer (NSCLC) TAF15 TEAD4

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Ubiquitin-specific protease 21 promotes tumorigenicity and stemness of colorectal cancer by deubiquitinating and stabilizing ZEB1

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 1006-1018页

作者： Jun-Jun Lin Ye-Cai Lu Department of Gastrointestinal Surgery Chaohu Hospital of Anhui Medical UniversityChaohu 238000Anhui ProvinceChina

BACKGROUND Colorectal cancer(CRC)is one very usual tumor together with higher death ***-specific protease 21(USP21)has been confirmed to take part into the regulation of CRC progression through serving as a ***,the promotive function of USP21 has also discovered in the progression of ***1 has illustrated to be modulated by USP7,USP22 and USP51 in ***,the regulatory functions of USP21 on ZEB1 in CRC progression need more *** To investigate the relationship between USP21 and ZEB1 in CRC *** The mRNA and protein expressions were assessed through RT-qPCR,western blot and IHC *** interaction between USP21 and ZEB1 was evaluated through Co-IP and GST pull down *** cell proliferation was detected through colony formation *** cell migration and invasion abilities were determined through Transwell *** stemness was tested through sphere formation *** tumor growth was evaluated through in vivo mice *** In this work,USP21 and ZEB1 exhibited higher expression in CRC,and resulted into poor ***,the interaction between USP21 and ZEB1 was further *** was demonstrated that USP21 contributed to the stability of ZEB1 through modulating ubiquitination *** addition,USP21 streng-thened cell proliferation,migration and stemness through regulating *** last,through in vivo assays,it was illustrated that USP21/ZEB1 axis aggravated tumor *** For the first time,these above findings manifested that USP21 promoted tumorigenicity and stemness of CRC by deubiquitinating and stabilizing *** discovery suggested that USP21/ZEB1 axis may provide novel sights for the treatment of CRC.

关键词： Ubiquitin-specific protease 21 ZEB1 Stemness Colorectal cancer

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Diagnostic and prognostic implications of non-high-density lipoprotein cholesterol and homocysteine levels for cognitive impairment in thalamic infarction

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World Journal of Psychiatry 2023年第12期13卷 985-994页

作者： Shan-Yao Zhu Wei Ge Huan Zhang Department of Internal Medicine-Neurology Chaohu Hospital Affiliated to Anhui Medical UniversityHefei 238000Anhui ProvinceChina

BACKGROUND Patients with thalamic infarction experience abnormal blockages of multinuc-leated vessels,affecting the body and thereby the *** patients with thalamic infarction have an adverse prognosis,which seriously affects their ***,it is essential to analyze the independent risk factors that influence the prognosis of patients with thalamic infarction and develop corresponding preventive *** To explore the effect of non-high-density lipoprotein cholesterol(non-HDL-C)and Homocysteine(Hcy)levels in cognitive impairment in thalamic *** From March 2019 to March 2022,80 patients with thalamic infarction were divided into a group with cognitive impairment[Montreal Cognitive Assessment(MoCA)score2).RESULTS The non-HDL-C and Hcy levels were significantly higher in the group with cognitive impairment than in the group with normal cognitive function(P0.05).The MoCA scores of the group with cognitive impairment were significantly lower than those of the group with normal cognitive function and the control group(P<0.05).There was a significant difference between the control group and the group with normal cognitive function(P<0.05).The non-HDL-C and Hcy levels were c

关键词： Thalamic infarction Cognitive impairment Non-high-density lipoprotein cholesterol High homocysteine level Diagnostic value Prognosis Influencing factors Correlation

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The effect of adjuvant chemotherapy in resectable cholangiocarcinoma: A meta-analysis and systematic review

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Hepatobiliary & Pancreatic Diseases International 2019年第2期18卷 110-116页

作者： Ming-Liang Wang Zhang-Yan Ke Shuai Yin Chen-Hai Liu Qiang Huang Department of General Surgery Affiliated Provincial Hospital of Anhui Medical University Department of Internal Medicine The First Affiliated Hospital of Anhui Medical University

Background: The benefit of adjuvant chemotherapy for resectable cholangiocarcinoma remains unclear due to the lack of randomized control studies. This study aimed to investigate the possible benefit of postoperative adjuvant chemotherapy for resectable cholangiocarcinoma. Data sources: Relevant research articles published before 1 st March 2018 in Pub Med, Embase and the Cochrane library databases were retrieved. Published data were extracted and analyzed by RevMan 5.3, and the results were presented as hazard ratios(HRs) [95% confidence intervals(CI)] and forest plots. Results: One prospective and eighteen retrospective studies were included, with a total number of 11,458 patients, 4696 of whom received postoperative chemotherapy. There was a significant improvement of the overall survival(OS) for patients who underwent operation + adjuvant chemotherapy compared to those who underwent operation alone(HR = 0.61; P < 0.001). Subgroup analyses show that the postoperative chemotherapy group compared with operation alone group are indicated as follows: hilar cholangiocarcinoma group(HR = 0.60; P < 0.001), intrahepatic cholangiocarcinoma group(HR = 0.60; P < 0.001), R1 resection group(HR = 0.71; P = 0.04), LN-positive diagnosis group(HR = 0.58; P < 0.001), gemcitabine-based chemotherapy group(HR = 0.42; P < 0.001), distal cholangiocarcinoma group(HR = 0.48; P = 0.17), R0 resection group(HR = 0.69; P = 0.43), and 5-flurouracil-based chemotherapy group(HR = 0.90; P = 0.66), respectively. Conclusions: Postoperative adjuvant chemotherapy can improve the OS in intrahepatic and hilar cholangiocarcinoma patients. However, distal cholangiocarcinoma patients gain no benefit from postoperative adjuvant chemotherapy. Prospective randomized trials are warranted in order to define the standard chemotherapy regimen.

关键词： Resectable cholangiocarcinoma Adjuvant chemotherapy Meta-analysis

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Psychometric hepatic encephalopathy score for diagnosis of minimal hepatic encephalopathy in China

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World Journal of Gastroenterology 2013年第46期19卷 8745-8751页

作者： Su-Wen Li Kai Wang Yong-Qiang Yu Hai-Bao Wang Yuan-Hai Li Jian-Ming Xu anhui Geriatric Institute of anhui medical university Department of Gastroenterology the First Affiliated HospitalAnhui Medical University Key Laboratory of Gastroenterology of anhui Province Department of Neurology the First Affiliated HospitalAnhui Medical University Department of Radiology the First Affiliated HospitalAnhui Medical University Department of Anaesthesiology the First Affiliated HospitalAnhui Medical University

AIM:To construct normal values for the tests of the psychometric hepatic encephalopathy score(PHES)and to evaluate its usefulness in the diagnosis of minimal hepatic encephalopathy(MHE)among Chinese individuals with ***:The five tests of PHES,number connection test-A(NCT-A),number connection test-B,serial dotting test,line tracing test and digit symbol test(DST),were administered to all enrolled subjects in a quiet room with sufficient *** subjects with overt HE were excluded by the West-Haven criteria and a detailed neurological *** on the nomograms of healthy volunteers,the patients were classified as having MHE when their PHES was less ***:In total,146 healthy volunteers completed all the PHES *** and education years were confirmed to be predictors of all five *** total,53patients with liver cirrhosis completed the *** the patients with liver cirrhosis,24(45.3%),22(41.5%)and 7(13.2%)had Child-Pugh grades A,B and C,*** was diagnosed in 26 patients(49.1%).Compared with compensated cirrhotic patients(Child A),decompensated cirrhotic patients(Child B and C)had a higher proportion of MHE(65.5%vs 29.2%).No differences in age and education years were found between the MHE and non-MHE ***-A and DST were able to diagnose MHE with a sensitivity of 76.9%and a specificity of 96.3%(AUC=0.866,K=0.735).CONCLUSION:The proportion of MHE is associated with liver ***-A and DST are simple tools that can be used for the diagnosis of MHE in China.

关键词： Cirrhosis Minimal hepatic encephalopa-thy Neuropsychological tests Psychometric hepatic encephalopathy score Number connection test Digit symbol test

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