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subretinal fibrosis secondary to neovascular age-related macular degeneration:mechanisms and potential therapeutic targets

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Neural Regeneration Research 2025年第2期20卷 378-393页

作者： Jingxiang Zhang Xia sheng Quanju Ding Yujun Wang Jiwei Zhao Jingfa Zhang Department of Ophthalmology People’s Hospital of Huangdao DistrictQingdaoShandong ProvinceChina Department of Urology People’s Hospital of Huangdao DistrictQingdaoShandong ProvinceChina Department of Ophthalmology Shanghai General Hospital(Shanghai First People’s Hospital)Shanghai Jiao Tong University School of MedicineShanghaiChina National Clinical Research Center for Eye Diseases Shanghai Key Laboratory of Ocular Fundus DiseasesShanghai Engineering Center for Visual Science and PhotomedicineShanghai Engineering Center for Precise Diagnosis and Treatment of Eye DiseasesShanghaiChina

subretinal fibrosis is the end-stage sequelae of neovascular age-related macular *** causes local damage to photoreceptors,retinal pigment epithelium,and choroidal vessels,which leads to permanent central vision loss of patients with neovascular age-related macular *** pathogenesis of subretinal fibrosis is complex,and the underlying mechanisms are largely ***,there are no effective treatment options.A thorough understanding of the pathogenesis of subretinal fibrosis and its related mechanisms is important to elucidate its complications and explore potential *** current article reviews several aspects of subretinal fibrosis,including the current understanding on the relationship between neovascular age-related macular degeneration and subretinal fibrosis;multimodal imaging techniques for subretinal fibrosis;animal models for studying subretinal fibrosis;cellular and non-cellular constituents of subretinal fibrosis;pathophysiological mechanisms involved in subretinal fibrosis,such as aging,infiltration of macrophages,different sources of mesenchymal transition to myofibroblast,and activation of complement system and immune cells;and several key molecules and signaling pathways participating in the pathogenesis of subretinal fibrosis,such as vascular endothelial growth factor,connective tissue growth factor,fibroblast growth factor 2,platelet-derived growth factor and platelet-derived growth factor receptor-β,transforming growth factor-βsignaling pathway,Wnt signaling pathway,and the axis of heat shock protein 70-Toll-like receptors 2/*** review will improve the understanding of the pathogenesis of subretinal fibrosis,allow the discovery of molecular targets,and explore potential treatments for the management of subretinal fibrosis.

关键词： choroidal neovascularization epithelial-mesenchymal transition mesenchymal transition myofibroblast neovascular age-related macular degeneration submacular fibrosis subretinal fibrosis therapeutic targets transforming growth factor-β vascular endothelial growth factor

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Correlation between cerebral neurotransmitters levels by proton magnetic resonance spectroscopy and HbA1c in patients with type 2 diabetes

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World Journal of Diabetes 2024年第6期15卷 1263-1271页

作者： Xiang-Yu Gao Chen-Xia Zhou Hong-Mei Li Min Cheng Da Chen Zi-Yi Li Bo Feng Jun song Department of Endocrinology East HospitalTongji University School of MedicineShanghai 200120China Department of Endocrinology Qilu Hospital(Qingdao)Cheeloo College of MedicineShandong UniversityQingdao 266000Shandong ProvinceChina Department of Immunization Program Huangdao District Center for Disease Prevention and ControlQingdao 266400Shandong ProvinceChina

BACKGROUND Cognitive dysfunction is the main manifestation of central *** cognitive impairments tend to be overlooked in patients with diabetes mellitus(DM),there is a growing body of evidence linking DM to cognitive *** is closely related to neurological abnormalities,while often disregarded in clinical *** in cerebral neurotransmitter levels are associated with a variety of neurological abnormalities and may be closely related to blood glucose control in patients with type 2 DM(T2DM).AIM To evaluate the concentrations of cerebral neurotransmitters in T2DM patients exhibiting different hemoglobin A1c(HbA1c)*** A total of 130 T2DM patients were enrolled at the Department of Endocrinology of shanghai East *** participants were divided into four groups according to their HbA1c levels using the interquartile method,namely Q1(sured,including age,height,weight,neck/waist/hip circumferences,blood pressure,comorbidities,duration of DM,and biochemical ***,neurotransmitters in the left hippocampus and left brainstem area were detected by proton magnetic resonance *** The HbA1c level was significantly associated with urinary microalbumin(mALB),triglyceride,low-density lipoprotein cholesterol(LDL-C),homeostasis model assessment of insulin resistance(HOMA-IR),and beta cell function(HOMA-β),N-acetylaspartate/creatine(NAA/Cr),and NAA/choline(NAA/Cho).spearman correlation analysis showed that mALB,LDL-C,HOMA-IR and NAA/Cr in the left brainstem area were positively correlated with the level of HbA1c(Ps HOMA-βwas negatively correlated with the HbA1c level(Pstic regression analysis showed that NAA/Cho[Odds ratio(OR):1.608,95%confidence interval(95%CI):1.004-2.578,P<0.05],LDL-C(OR:1.627,95%CI:1.119-2.370,P<0.05),and HOMA-IR(OR:1.107,95%CI:1.031-

关键词： Type 2 diabetes mellitus Hemoglobin A1c Proton magnetic resonance spectroscopy Neurotransmitters Central neuropathy

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Changes in the Non-targeted Metabolomic Profile of Three-year-old Toddlers with Elevated Exposure to Polycyclic Aromatic Hydrocarbons

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Biomedical and Environmental sciences 2024年第5期37卷 479-493页

作者： LI Yang LIN Dan ZHANG Xiu Qin JU Guang Xiu sU Ya ZHANG Qian DUAN Hai Ping YU Wei sen WANG Bing Ling PANG shu Tao Department of Epidemiology and Health statistics School of Public HealthQingdao UniversityQingdao 266021ShandongChina Department of Environmental Health Qingdao Municipal Center for Disease Control and PreventionQingdao Institute of Preventive MedicineQingdao 266033ShandongChina Physicochemical Laboratory Qingdao Municipal Center for Disease Control and PreventionQingdao Institute of Preventive MedicineQingdao 266033ShandongChina section of Child Health Care Huangdao Maternity and Child Health Care Hospital of QingdaoQingdao 266499ShandongChina qingdao Blood Center Qingdao 266071ShandongChina

Objective To investigate changes in the urinary metabolite profiles of children exposed to polycyclic aromatic hydrocarbons(PAHs)during critical brain development and explore their potential link with the intestinal *** Liquid chromatography-tandem mass spectrometry was used to determine ten hydroxyl metabolites of PAHs(OH-PAHs)in 36-month-old ***,37 children were categorized into low-and high-exposure groups based on the sum of the ten ***-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was used to identify non-targeted metabolites in the urine ***,fecal flora abundance was assessed by 16s rRNA gene sequencing using Illumina *** The concentrations of 21 metabolites were significantly higher in the high exposure group than in the low exposure group(variable importance for projection>1,Pst of these metabolites were positively correlated with the hydroxyl metabolites of naphthalene,fluorine,and phenanthrene(r=0.336–0.531).The identified differential metabolites primarily belonged to pathways associated with inflammation or proinflammatory states,including amino acid,lipid,and nucleotide ***,these distinct metabolites were significantly associated with specific intestinal flora abundances(r=0.34–0.55),which were mainly involved in *** Higher PAH exposure in young children affected metabolic homeostasis,particularly that of certain gut microbiota-derived *** investigation is needed to explore the potential influence of PAHs on the gut microbiota and their possible association with neurodevelopmental outcomes.

关键词： Child Gut microbiota Non-targeted metabolomics Polycyclic aromatic hydrocarbons Urinary metabolite profile

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A multicenter prospective study on the management of hepatoblastoma in children:a report from the Chinese Children's Cancer Group

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World Journal of Pediatrics 2024年第6期20卷 590-601页

作者： Meng-Jie Tang Xiao-Li Ma Xiang-Ling He Wei-Hua Pan Xiao-Hong Zhang sha-Yi Jiang Ju Gao Fu Lie Wei Yao song Gu Wei-Ling Zhang Qiang Zhao shi-Hao Huang Yong-Jun Fang Wei Liu Hui-Zhong Niu Chun-Mei Wang Li-Rong sun Hui Gao Yun-Peng Dai shun-Gen Huang Zhi-Yong Zhong Xi-Ge Wang Zhong-Rong Li Liang-Chun Yang Ye-Ming Wu Huan-Min Wang Xin sun Xiao-Jun Yuan Department of Pediatric Hematology/Oncology Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineNo.1665Kongjiang RoadYangpu DistrictShanghai 200092China Medical Oncology Department Pediatric Oncology CenterBeijing Children's HospitalCapital Medical UniversityNational Center for Children's HealthBeijing 100045China Department of Hematology/Oncology Children's Medical CenterHunan Provincial People's HospitalThe First Affiliated Hospital of Hunan Normal UniversityChangsha 41005China Department of Pediatric surgery Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200092China Department of Hematology/Oncology Guangzhou Women and Children's Medical CenterNational Children's Medical Center for South Central RegionGuangzhou 510623China Department of Hematology Shanghai Children's HospitalShanghai Jiao Tong UniversityShanghai 200062China Department of Pediatrics West China Second University HospitalSichuan UniversityChengdu 610041China Department of Hematology/Oncology Qilu Children's Hospital of Shandong UniversityJinan 250022China Department of Pediatric surgery Children's Hospital of Fudan UniversityShanghai 201102China Department of General surgery Shanghai Children's Medical Center(National Children's Medical Center-Shanghai)Shanghai Jiao Tong University School of MedicineShanghai 200127China Department of Pediatrics Beijing Tongren HospitalCapital Medical UniversityBeijing 100730China Department of Pediatric Oncology Tianjin Medical University Cancer Institute and HospitalTianjin 300060China Department of Hematology/Oncology Children's Hospital of Nanjing Medical UniversityNanjing 210008China Department of Hematology/Oncology Henan Children's HospitalZhengzhou 450018China Department of Pediatric General surgery Hebei Children's Hospital of Hebei Medical UniversityShijiazhuang City 050031China Children's hospital the First Affliated Hospital of Zhengzhou UniversityZhengzhou 450052China Department of Paediatric

Background This study aimed to identify survival risk factors in Chinese children with hepatoblastoma(HB)and assess the effectiveness of the new treatment protocol proposed by the Chinese Children's Cancer Group(CCCG)in *** A multicenter,prospective study that included 399 patients with HB from January 2015 to June 2020 was *** demographics,treatment protocols,and other related information were *** regression models and Kaplan-Meier curve methods were *** The 4-year event-free survival(EFs)and overall survival(Os)were 76.9 and 93.5%,*** 4-year EFs rates for the very-low-risk,low-risk,intermediate-risk,and high-risk groups were 100%,91.6%,81.7%,and 51.0%,*** 4-year 0s was 100%,97.3%,94.4%,and 86.8%,*** regression analysis found that age,tumor rupture(R+),and extrahepatic tumor extension(E+)were independent prognostic factors.A total of 299 patients had complete remission,and 19 *** with declining alpha-fetoprotein(AFP)>75%after the first two cycles of neoadjuvant chemotherapy had a better EFs and Os than those≤75%.Conclusions The survival outcome of HB children has dramatically improved since the implementation of CCCG-HB-2016 ***≥8 years,R+,and E+were independent risk factors for *** with a declining AFP>75%after the first two cycles of neoadjuvant chemotherapy had better EFs and Os.

关键词： Alpha-fetoprotein Hepatoblastoma Multicenter Prospective study survival

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Clinical Efficacy Analysis of Tiotropium Bromide Combined with Budesonide and Formoterol Inhalation in Treating COPD

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Journal of Clinical and Nursing Research 2024年第1期8卷 1-6页

作者： Hailing Lin Yanjie Lu qingdao shibei district people’s hospital Qingdao 266011Shandong ProvinceChina

Objective:To analyze the clinical efficacy of tiotropium bromide(TB)combined with budesonide formoterol(BUD/FM)inhalation in treating chronic obstructive pulmonary disease(COPD).Methods:62 COPD patients admitted to the hospital between June 2020 and December 2022 were selected as samples for this *** patients were divided into a combination group and a conventional group using the random number table method,with 31 cases in each *** patients in the combination group were treated with TB combined with BUD/FM inhalation,whereas the patients in the conventional group were treated with BUD/FM inhalation *** treatment efficacy and changes in lung function indicators of both groups were ***:The total efficacy of treatment in the combined group was higher than that in the conventional group,and the difference was statistically significant(Ps no difference in pulmonary function indicators between the two groups(P>0.05).After three months of treatment,all lung function indicators of the combined group were higher than those of the conventional group,and the difference was statistically significant(Psion:Combining TB with BUD/FM inhalation therapy increases the efficacy of treatment for patients with ***,it also improves lung function and leads to a better prognosis.

关键词： Tiotropium bromide Budesonide formoterol Inhalation therapy Chronic obstructive pulmonary disease

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GTF2H4 regulates partial EndMT via NF-κB activation through NCOA3 phosphorylation in ischemic diseases

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The Innovation 2024年第2期5卷 27-41页

作者： Zheyan Fang Gang Zhao shuang Zhao Xueting Yu Runyang Feng You-en Zhang Haomin Li Lei Huang Zhenyang Guo Zhentao Zhang Mukaddas Abdurahman Hangnan Hong Peng Li Bing Wu Jinhang Zhu Xin Zhong Dong Huang Hao Lu Xin Zhao Zhaoyang Chen Wenbin Zhang Junjie Guo Hongchao Zheng Yue He shengying Qin Haojie Lu Yun Zhao Xiangdong Wang Junbo Ge Hua Li Department of Cardiology Zhongshan HospitalFudan UniversityShanghai Institute of Cardiovascular DiseasesShanghai 200032China Department of Cardiology Zhongshan HospitalFudan UniversityShanghai 200032China Department of Medical Examination Shanghai Xuhui District Central HospitalShanghai 200031China Department of Cardiology and Institute of Clinical Medicine Renmin HospitalHubei University of MedicineShiyan 442000China Clinical Data Center Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhou 310052China Department of Molecular Celland Cancer BiologyUniversity of Massachusetts Chan Medical SchoolWorcesterMA 01605USA Bio-X Institute Key Laboratory for The Genetics of Developmental and Neuropsychiatric DisordersShanghai Jiao Tong UniversityShanghai 200030China Department of Cardiology Heart Center of Fujian ProvinceFujian Medical University Union HospitalFuzhou 350001China Department of Cardiology Sir Run Run Shaw Hospitalaffiliated with Zhejiang University School of MedicineHangzhou 310020China Department of Cardiology The Affiliated Hospital of Qingdao UniversityQingdao 266003China Department of Cardiology Shanghai Xuhui District Central HospitalShanghai 200031China Department of Cardiology Shanghai Eighth People’s HospitalShanghai 200235China Department of Chemistry and Institutes of Biomedical sciences Fudan UniversityShanghai 200032China state Key Laboratory of Cell Biology Shanghai Institute of Biochemistry and Cell BiologyCenter for Excellence in Molecular Cell ScienceChinese Academy of SciencesUniversity of Chinese Academy of SciencesShanghai 200031China school of Life science and Technology Shanghai Tech University100 Haike RoadShanghai 201210China Key Laboratory of systems Health science of Zhejiang Province School of Life ScienceHangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhou 310024China Department of Pulmonary and Critical Care Medicine Zhongshan Hospital

Partial endothelial-to-mesenchymal transition(EndMT)is an intermediate phenotype observed in endothelial cells(ECs)undergoing a transition toward a mesenchymal state to support neovascularization during(patho)physiological ***,we investigated the occurrence of partial EndMT in ECs under hypoxic/ischemic conditions and identified general transcription factor IIH subunit 4(GTF2H4)as a positive regulator of this *** addition,we discovered that GTF2H4 collaborates with its target protein excision repair cross-complementation group 3(ERCC3)to co-regulate partial ***,by using phosphorylation proteomics and site-directed mutagenesis,we demonstrated that GTF2H4 was involved in the phosphorylation of receptor coactivator 3(NCOA3)at serine 1330,which promoted the interaction between NCOA3 and p65,resulting in the transcriptional activation of NF-κB and the NF-kB/snail signaling axis during partial *** vivo experiments confirmed that GTF2H4 significantly promoted partial EndMT and angiogenesis after ischemic ***,our findings reveal that targeting GTF2H4 is promising for tissue repair and offers potential opportunities for treating hypoxic/ischemic diseases.

关键词： ischemic activation GTF

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Effects of creep characteristics of natural gas hydrate-bearing sediments on wellbore stability

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Petroleum science 2022年第1期19卷 220-233页

作者： Yang Li Yuan-Fang Cheng Chuan-Liang Yan Zhi-Yuan Wang Li-Fang song school of Petroleum Engineering China University of Petroleum(East China)66 West Changjiang RoadHuangdao DistrictQingdao 266000China

Natural gas hydrate(NGH)reservoirs consist of the types of sediments with weak cementation,low strength,high plasticity,and high *** on the kinetics and thermodynamic characteristics of NGH decomposition,herein a heat-fluid-solid coupling model was established for studying the wellbore stability in an NGH-bearing formation to analyze the effects of the creep characteristics of NGH-bearing sediments during long-term *** results demonstrated that the creep characteristics of sediments resulted in larger plastic yield range,thus aggravating the plastic strain accumulation around the ***,the creep characteristics of NGH-bearing sediments could enhance the effects induced by the difference in horizontal in situ stress,as a result,the plastic strain in the formation around the wellbore increased nonlinearly with increasing difference in in situ *** lower the pore pressure,the greater the stress concentration effects and the higher the plastic strain at the ***,the lower the initial NGH saturation,the greater the initial plastic strain and yield range and the higher the equivalent creep *** plastic strain at the wellbore increased nonlinearly with decreasing initial saturation.

关键词： Natural gas hydrates Wellbore stability Creep Plastic yield

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Conversion immunotherapy for deficient mismatch repair locally unresectable colon cancer:A case report

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World Journal of Gastrointestinal Oncology 2023年第12期15卷 2237-2241页

作者： Zhen sun He Liu Guan-Nan Zhang Yi Xiao Division of Colorectal surgery Department of General SurgeryPeking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China Department of Gastrointestinal surgery The People's Hospital of Huangdao DistrictQingdao 266400Shandong ProvinceChina

BACKGROUND Owing to the special features of biologics,deficient mismatch repair(dMMR)in patients with colon cancer has achieved little treatment efficacy from *** has shown promising results for the treatment of colon *** high response rate observed suggests a great option for patients presenting with unresectable tumors,as it allows for better oncological ***,we aimed to highlight the significant effects of immunotherapy on dMMR in colon *** sUMMARY A 54-year-old man diagnosed with locally unresectable dMMR colon cancer received preoperative immunotherapy(three cycles of pembrolizumab)and achieved a pathological complete response after *** Immunotherapy can be used as a conversion treatment for locally unresectable colon cancer with dMMR.

关键词： Colon cancer Immunotherapy Pathological complete response Case report

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Recent progress in molecular mechanisms of postoperative recurrence and metastasis of hepatocellular carcinoma

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World Journal of Gastroenterology 2022年第46期28卷 6433-6477页

作者： Zhao-shan Niu Wen-Hong Wang Xiao-Jun Niu Laboratory of Micromorphology School of Basic MedicineQingdao UniversityQingdao 266071Shandong ProvinceChina Department of Pathology School of Basic MedicineQingdao UniversityQingdao 266071Shandong ProvinceChina Department of Internal Medicine Qingdao Shibei District People's HospitalQingdao 266033Shandong ProvinceChina

Hepatectomy is currently considered the most effective option for treating patients with early and intermediate hepatocellular carcinoma(HCC).Unfortunately,the postoperative prognosis of patients with HCC remains unsatisfactory,predominantly because of high postoperative metastasis and recurrence ***,research on the molecular mechanisms of postoperative HCC metastasis and recurrence will help develop effective intervention measures to prevent or delay HCC metastasis and recurrence and to improve the long-term survival of HCC ***,we review the latest research progress on the molecular mechanisms underlying postoperative HCC metastasis and recurrence to lay a foundation for improving the understanding of HCC metastasis and recurrence and for developing more precise prevention and intervention strategies.

关键词： Hepatocellular carcinoma Recurrence Metastasis Mechanisms Postoperation Intervention

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Therapeutic efficacy and safety of various botulinum toxin A doses and concentrations in spastic foot after stroke: a randomized controlled trial

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Neural Regeneration Research 2017年第9期12卷 1451-1457页

作者： Jiang Li Ru Zhang Bo-li Cui Yong-xiang Zhang Guang-tao Bai si-shan Gao Wen-jian Li Affiliated hospital of qingdao University Department of Neurology Traditional Medicine Hospital of Huangdao District

No recommended guidelines currently exist for the therapeutic concentration or dose of botulinum toxin type A （BTXA） injected into the muscle to treat limb spasticity. Therefore, in this randomized controlled trial, we explored the safety and efficacy of two concentrations and two doses of BTXA in the treatment of spastic toot after stroke to optimize this treatment in these patients. Eligible patients （n = 104） were randomized into four groups. The triceps surae and tibialis posterior on the affected side were injected with BTXA at one of two doses （200 U or 400 U） and two concentrations （50 U/mL or 100 U/mL）. 2he following assessments were conducted before as well as 4 days and 1, 2, 4, and 12 weeks after treatment： spasticity, assessed using the modified Ashworth scale; basic functional mobility, assessed using a timed up and go test; pace, assessed using a 10-meter timed walking test; and the ability to walk, assessed using Holden＇s graded scale and a visual analog scale. The reported results are based on the 89 patients that completed the study. We found significant differences for the two doses and concentrations of BTXA to improve the ability of patients to walk independently, with the high-dose/low-concentration combination providing the best effect. Onset and duration of the ameliorating effects of BTXA were 4-7 days and 12 weeks, respectively. Thus, BTXA effectively treated foot spasms after stroke at an optimal dose of 400 U and concentration of 50 U/mL.

关键词： nerve regeneration stroke Jbot spasms botulinum toxin type A foot varus foot drop walking function neural regeneration

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