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Predicting Diabetic Retinopathy Using a Machine Learning Approach Informed by Whole-Exome Sequencing Studies

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Biomedical and Environmental Sciences 2025年第1期38卷 67-78页

作者： Chongyang She Wenying Fan Yunyun Li Yong Tao Zufei Li Department of Ophthalmology Beijing Chao-Yang HospitalCapital Medical UniversityBeijing 100020China Beijing Tongren Eye Center Beijing Tongren HospitalCapital Medical UniversityBeijing 100176China Department of Otorhinolaryngology Head and Neck SurgeryBeijing Chao-Yang HospitalCapital Medical UniversityBeijing 100020China

Objective To establish and validate a novel diabetic retinopathy(DR)risk-prediction model using a whole-exome sequencing(WES)-based machine learning(ML)*** WES was performed to identify potential single nucleotide polymorphism(SNP)or mutation sites in a DR pedigree comprising 10 members.A prediction model was established and validated in a cohort of 420 type 2 diabetic patients based on both genetic and demographic *** contribution of each feature was assessed using Shapley Additive explanation *** efficacies of the models with and without SNP were *** WES revealed that seven SNPs/mutations(rs116911833 in TRIM7,1997T>C in LRBA,1643T>C in PRMT10,rs117858678 in C9orf152,rs201922794 in CLDN25,rs146694895 in SH3GLB2,and rs201407189 in FANCC)were associated with ***,the model including rs146694895 and rs201407189 achieved better performance in predicting DR(accuracy:80.2%;sensitivity:83.3%;specificity:76.7%;area under the receiver operating characteristic curve[AUC]:80.0%)than the model without these SNPs(accuracy:79.4%;sensitivity:80.3%;specificity:78.3%;AUC:79.3%).Conclusion Novel SNP sites associated with DR were identified in the DR *** of rs146694895 and rs201407189 significantly enhanced the performance of the ML-based DR prediction model.

关键词： Machine learning Diabetic retinopathy Whole exome sequencing Type 2 diabetes mellitus

Purinergic signaling by TCRaβ~+double-negative T regulatory cells ameliorates liver ischemia–reperfusion injury

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Science Bulletin 2025年第2期70卷 241-254页

作者： Hua Jin Mingyang Li Xiyu Wang Lu Yang Xinjie Zhong Zihan Zhang Xiaotong Han Jingjing Zhu Mengyi Li Songlin Wang Simon C.Robson Guangyong Sun Dong Zhang Immunology Research Center for Oral and Systemic Health Beijing Friendship HospitalCapital Medical UniversityBeijing 100050China medical Research Center Beijing Institute of Respiratory Medicine and Beijing Chao-Yang HospitalCapital Medical UniversityBeijing 100020China Department of Gastroenterology Beijing Chao-Yang HospitalCapital Medical UniversityBeijing 100020China General Surgery Department Beijing Friendship HospitalCapital Medical UniversityBeijing 100050China Beijing Laboratory of Oral Health Capital Medical University School of Basic MedicineBeijing 100069China Center for Inflammation Research Department of AnesthesiaCritical Care&Pain Medicineand Department of MedicineBeth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMA 02115USA

Hepatic ischemia–reperfusion injury(HIRI)is an important cause of liver injury following liver transplantation and major resections,and neutrophils are the key effector cells in ***-negative T regulatory cells(DNT)are increasingly recognized as having critical regulatory functions in the immune *** DNT expresses distinct immunoregulatory mechanisms to modulate neutrophils,as in HIRI,remains largely *** this study,we found that murine and human DNT highly expressed CD39that protected DNT from extracellular ATP-induced apoptosis and generated adenosine in tandem with CD73,to induce high levels of neutrophil ***,extracellular adenosine enhanced DNT survival and suppressive function by upregulating survivin and NKG2D expression via the A2AR/pAKT/FOXO1 signaling *** transfer of DNT ameliorated HIRI in mice through the inhibition of neutrophils in a CD39-dependent ***,the adoptive transfer of A2ar^(-/-)DNT validated the importance of adenosine/A2AR signaling,in promoting DNT survival and immunomodulatory function to protect against HIRI in *** conclusion,purinergic signaling is crucial for DNT homeostasis in *** of CD39 or activation of A2AR signaling in DNT may provide novel therapeutic strategies to target innate immune disorders.?2024 The *** by Elsevier *** behalf of Science China *** is an open accessarticle under the CC BY-NC-ND license(http://***/licenses/by-nc-nd/4.0/).

关键词： Double-negative T regulatory cells Hepatic ischemia and reperfusion injury CD39 Adenosine A2AR

FUBP3 mediates the amyloid-β-induced neuronal NLRP3 expression

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Neural Regeneration Research 2025年第7期20卷 2068-2083页

作者： Jing Yao Yuan Li Xi Liu Wenping Liang Yu Li Liyong Wu Zhe Wang Weihong Song The National Clinical Research Center for Geriatric Disease Xuanwu HospitalCapital Medical UniversityBeijingChina Department of Neurology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina Department of Neurosurgery Xuanwu HospitalCapital Medical UniversityBeijingChina Department of Pediatrics The Second Affiliated Hospital and Yuying Children’s HospitalKey Laboratory of Alzheimer’s Disease of Zhejiang ProvinceInstitute of AgingWenzhou Medical UniversityWenzhouZhejiang ProvinceChina Oujiang Laboratory(Zhejiang Laboratory for Regenerative Medicine Visionand Brain Health)WenzhouZhejiang ProvinceChina

Alzheimer's disease is characterized by deposition of amyloid-β,which forms extracellular neuritic plaques,and accumulation of hyperphosphorylated tau,which aggregates to form intraneuronal neurofibrillary tangles,in the *** NLRP3 inflammasome may play a role in the transition from amyloid-βdeposition to tau phosphorylation and *** NLRP3 is primarily found in brain microglia,and tau is predominantly located in neurons,it has been suggested that NLRP3 expressed by microglia indirectly triggers tau phosphorylation by upregulating the expression of pro-inflammatory ***,we found that neurons also express NLRP3 in vitro and in vivo,and that neuronal NLRP3 regulates tau *** biochemical methods,we mapped the minimal NLRP3 promoter and identified FUBP3 as a transcription factor regulating NLRP3 expression in *** primary neurons and the neuroblastoma cell line Neuro2A,FUBP3 is required for endogenous NLRP3 expression and tau phosphorylation only when amyloid-βis *** the brains of aged wild-type mice and a mouse model of Alzheimer's disease,FUBP3 expression was markedly increased in cortical *** analysis suggested that FUBP3 plays a role in neuron-mediated immune *** also found that FUBP3 trimmed the 5′end of DNA fragments that it bound,implying that FUBP3 functions in stress-induced *** findings suggest that neuronal NLRP3 may be more directly involved in the amyloid-β-to–phospho-tau transition than microglial NLRP3,and that amyloid-βfundamentally alters the regulatory mechanism of NLRP3 expression in *** that FUBP3 was only expressed at low levels in young wild-type mice and was strongly upregulated in the brains of aged mice and Alzheimer's disease mice,FUBP3 could be a safe therapeutic target for preventing Alzheimer's disease progression.

关键词： 5′end trimming Alzheimer's disease amyloid-beta amyloid-β-dependent transcription FUBP3 inflammasome inflammation neuron NLRP3 tau transcription factor

Acupuncture Combined with Periocular Injection for Treatment of Hydroxychloroquine Retinopathy with Cystoid Macular Edema:A Case Report

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Chinese Journal of Integrative Medicine 2025年第1期31卷 68-72页

作者： LI Tian-tian WU Yan YANG Ying-xin XUE Yu-xin MA Chao-ting Department of Ophthalmology Beijing Hospital of Traditional Chinese MedicineCapital Medical UniversityBeijing100010China

Hydroxychloroquine(HCQ)is widely used in the treatment of autoimmune disorders such as systemic lupus erythematosus(SLE)and rheumatoid arthritis,and in recent years it has also been used in diseases such as cancer,neurodegenerative diseases,metabolic diseases,and microbial infections.(1)Due to the complex pharmacokinetic characteristics of HCQ,overdose or long-term use of the drug will lead to accumulation in the tissue of organism,and severe HCQ-related retinal toxicity may occur.A cohort study in America showes that after 10 and 15 years of HCQ use,the incidence of HCQ retinopathy will be 2.5%and 8.6%,respectively.(2)The clinical manifestations of HCQ retinopathy are various,mainly photoreceptor and retinal pigment epithelium(RPE)defects,some combined with cystoid macular edema(CME),and ireversible central vision loss.

关键词： Acupuncture diseases epithelium

Gut microbiome composition in patients with liver cirrhosis with and without hepatic encephalopathy: A systematic review and metaanalysis

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World Journal of Hepatology 2025年第1期17卷 96-111页

作者： Xiao-Tong Xu Min-Jie Jiang Yun-Lai Fu Fang Xie Jian-Jun Li Qing-Hua Meng Beijing Institute of Hepatology Beijing YouAn HospitalCapital Medical UniversityBeijing 100069China Interventional Therapy Center for Oncology Beijing YouAn HospitalCapital Medical UniversityBeijing 100069China Department of Infectious Diseases Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinan 250000Shandong ProvinceChina

BACKGROUND The gut microbiome is associated with hepatic encephalopathy(HE),but research results on the gut microbiome characteristics of patients with liver cirrhosis with and without HE are *** To study the gut microbiota characteristics of patients with liver cirrhosis with and without *** We searched the PubMed,Web of Science,EMBASE,and Cochrane databases using two keywords,HE,and gut *** to the inclusion and exclusion criteria,suitable literature was screened to extract data on the diversity and composition of the fecal microbiota in patients with liver cirrhosis with and without *** data were analyzed using RevMan and *** Seventeen studies were included:(1)A meta-analysis of 7 studies revealed that the Shannon index in liver cirrhosis patients with HE was significantly lower than that in patients without HE[-0.20,95%confidence interval(CI):-0.28 to-0.13,I2=20%];(2)The relative abundances of Lachnospiraceae(-2.73,95%CI:-4.58 to-0.87,I2=38%)and Ruminococcaceae(-2.93,95%CI:-4.29 to-1.56,I2=0%)in liver cirrhosis patients with HE was significantly lower than those in patients without HE;(3)In patients with HE,Enterococcus,Proteobacteria,Enterococcaceae,and Enterobacteriaceae proportions increased,but Ruminococcaceae,Lachnospiraceae,Prevotellaceae,and Bacteroidetes proportions decreased;(4)Differences in the fecal metabolome between liver cirrhosis patients with and without HE were detected;and(5)Differential gut microbiomes may serve as diagnostic and prognostic *** The gut microbiomes of patients with liver cirrhosis with and without HE *** gut microbiomes may distinguish liver cirrhosis patients with or without HE and determine patient prognosis.

关键词： Gut microbiome Cirrhosis Hepatic encephalopathy Review Meta-analysis

Epigenetic regulation of the inflammatory response in stroke

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Neural Regeneration Research 2025年第11期20卷 3045-3062页

作者： Jingyi Liang Fei Yang Zixiao Li Qian Li School of Basic medical Sciences Capital Medical UniversityBeijingChina Department of Neurobiology School of Basic Medical SciencesCapital Medical UniversityBeijingChina Laboratory for Clinical Medicine Beijing Key Laboratory of Neural Regeneration and RepairCapital Medical UniversityBeijingChina Department of Neurology Beijing Tiantan HospitalCapital Medical UniversityBeijingChina China National Clinical Research Center for Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina National Center for Healthcare Quality Management in Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Chinese Institute for Brain Research BeijingChina Research Unit of Artificial Intelligence in Cerebrovascular Disease Chinese Academy of Medical SciencesBeijingChina Beijing Engineering Research Center of Digital Healthcare for Neurological Diseases BeijingChina Department of Biochemistry and Molecular Biology School of Basic Medical SciencesCapital Medical UniversityBeijingChina Beijing Key Laboratory of Cancer Invasion and Metastasis Research Capital Medical UniversityBeijingChina

Stroke is classified as ischemic or hemorrhagic,and there are few effective treatments for either *** mechanisms play a critical role in secondary brain injury following a stroke,which manifests as cytokine release,blood–brain barrier disruption,neuronal cell death,and ultimately behavioral *** the inflammatory response has been shown to mitigate this cascade of events in experimental stroke ***,in clinical trials of anti-inflammatory agents,longterm immunosuppression has not demonstrated significant clinical benefits for *** may be attributable to the dichotomous roles of inflammation in both tissue injury and repair,as well as the complex pathophysiologic inflammatory processes in *** acute harmful inflammatory responses or inducing a phenotypic shift from a pro-inflammatory to an anti-inflammatory state at specific time points after a stroke are alternative and promising therapeutic *** agents that can modulate inflammation requires a detailed understanding of the inflammatory processes of ***,epigenetic reprogramming plays a crucial role in modulating post-stroke inflammation and can potentially be exploited for stroke *** this review,we summarize current findings on the epigenetic regulation of the inflammatory response in stroke,focusing on key signaling pathways including nuclear factor-kappa B,Janus kinase/signal transducer and activator of transcription,and mitogen-activated protein kinase as well as inflammasome *** also discuss promising molecular targets for stroke *** evidence to date indicates that therapeutic targeting of the epigenetic regulation of inflammation can shift the balance from inflammation-induced tissue injury to repair following stroke,leading to improved post-stroke outcomes.

关键词： DNA methylation histone modification intracerebral hemorrhage ischemic stroke neuroinflammation neuroprotection non-coding RNA RNA methylation subarachnoid hemorrhage treatment

High-dose dexamethasone regulates microglial polarization via the GR/JAK1/STAT3 signaling pathway after traumatic brain injury

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Neural Regeneration Research 2025年第9期20卷 2611-2623页

作者： Mengshi Yang Miao Bai Yuan Zhuang Shenghua Lu Qianqian Ge Hao Li Yu Deng Hongbin Wu Xiaojian Xu Fei Niu Xinlong Dong Bin Zhang Baiyun Liu Beijing Tiantan hospital Capital Medical UniversityBeijingChina Department of Neurology The First Hospital of Tsinghua UniversityBeijingChina Department of Neurotrauma and Beijing Key Laboratory of Central Nervous System Injury Beijing Neurosurgical InstituteCapital Medical UniversityBeijingChina Department of Critical Care Medicine Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Center for Nerve Injury and Repair Beijing Institute of Brain DisordersChina National Clinical Research Center for Neurological DiseasesBeijingChina

Although microglial polarization and neuroinflammation are crucial cellular responses after traumatic brain injury,the fundamental regulatory and functional mechanisms remain insufficiently *** potent anti-inflammato ry agents,the use of glucoco rticoids in traumatic brain injury is still controversial,and their regulatory effects on microglial polarization are not yet *** the present study,we sought to determine whether exacerbation of traumatic brain injury caused by high-dose dexamethasone is related to its regulatory effects on microglial polarization and its mechanisms of *** vitro cultured BV2 cells and primary microglia and a controlled cortical impact mouse model were used to investigate the effects of dexamethasone on microglial ***,dexamethasone,RU486(a glucocorticoid receptor antagonist),and ruxolitinib(a Janus kinase 1 antagonist)were ***-sequencing data obtained from a C57BL/6 mouse model of traumatic brain injury were used to identify potential targets of *** Morris water maze,quantitative reverse transcription-polymerase chain reaction,western blotting,immunofluorescence and confocal microscopy analysis,and TUNEL,Nissl,and Golgi staining were performed to investigate our ***-throughput sequencing results showed that arginase 1,a marker of M2 microglia,was significantly downregulated in the dexamethasone group compared with the traumatic brain injury group at3 days post-traumatic brain *** dexamethasone inhibited M1 and M2 microglia,with a more pronounced inhibitory effect on M2microglia in vitro and in *** receptor plays an indispensable role in microglial polarization after dexamethasone treatment following traumatic brain ***,glucocorticoid receptor activation increased the number of apoptotic cells and neuronal death,and also decreased the density of dendritic spines.A possible downstream receptor signaling mechanism is th

关键词： apoptosis BV2 microglia dexamethasone glucocorticoid receptor glucocorticoids innate immune system microglial polarization neuroinflammation primary microglia traumatic brain injury

Decreased levels of phosphorylated synuclein in plasma are correlated with poststroke cognitive impairment

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Neural Regeneration Research 2025年第9期20卷 2598-2610页

作者： Yi Wang Yuning Li Yakun Gu Wei Ma Yuying Guan Mengyuan Guo Qianqian Shao Xunming Ji Jia Liu Department of Clinical Laboratory Beijing Bo’ai HospitalChina Rehabilitation Research CenterCapital Medical UniversityBeijingChina Beijing Institute of Brain Disorders Laboratory of Brain DisordersMinistry of Science and TechnologyCollaborative Innovation Center for Brain DisordersBeijing Advanced Innovation Center for Big Data-based Precision MedicineCapital Medical UniversityBeijingChina Department of Neurosurgery Xuanwu HospitalCapital Medical UniversityBeijingChina

Poststro ke cognitive impairment is a major secondary effect of ischemic stroke in many patients;however,few options are available for the early diagnosis and treatment of this *** aims of this study were to(1)determine the specific relationship between hypoxic andα-synuclein during the occur of poststroke cognitive impairment and(2)assess whether the serum phosphorylatedα-synuclein level can be used as a biomarker for poststro ke cognitive *** found that the phosphorylatedα-synuclein level was significantly increased and showed pathological aggregation around the cerebral infa rct area in a mouse model of ischemic *** addition,neuronalα-synuclein phosphorylation and aggregation were observed in the brain tissue of mice subjected to chronic hypoxia,suggesting that hypoxia is the underlying cause ofα-synuclein-mediated pathology in the brains of mice with ischemic *** phosphorylatedα-synuclein levels in patients with ischemic stroke were significantly lower than those in healt hy subjects,and were positively correlated with cognition levels in patients with ischemic ***,a decrease in serum high-density lipoprotein levels in stroke patie nts was significantly correlated with a decrease in phosphorylatedα-synuclein *** ischemic stroke mice did not show significant cognitive impairment or disrupted lipid metabolism 14 days after injury,some of them exhibited decreased cognitive function and reduced phosphorylatedα-synuclein *** together,our results suggest that serum phosphorylatedα-synuclein is a potential biomarker for poststroke cognitive impairment.

关键词： biomarker high-density lipoprotein ischemic stroke phosphorylatedα-synuclein poststroke cognitive impairment

Guidelines for standard operation of imaging modalities in orbital diseases (2024)

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International Journal of Ophthalmology(English edition) 2025年第1期18卷 51-66页

作者： Yi Shao Jian-Min Ma Xiao-Ming Huang Expert Workgroup of Guidelines for the useof imaging equipment in orbital diseases(2024) Ophthalmic Imaging and IntelligentMedicine Branch Chinese Medicine Education Association Ocular Oncology Committee of theOphthalmology Branch of the Chinese medical Doctor Association Ophthalmology Committee ofInternational Association of Translational Medicine Chinese Ophthalmic Imaging Study Groups Department of Ophthalmology Shanghai General HospitalShanghai Jiao Tong University School of MedicineNational Clinical Research Center for Eye DiseasesShanghai 200080China Beijing Tongren hospital affiliated to capital medical university Beijing 100005China Sichuan Eye hospital Chendu 610047Sichuan ProvinceChina 不详

Orbital disorders include conditions originating from the orbital bones,surrounding tissues,and post-orbital *** also include systemic ailments affecting the *** clinical symptoms make up the complex range of orbital *** these disorders mostly impact the orbital area instead of the intraocular compartment,there is little diagnostic usefulness for typical ophthalmic visual *** such,the vital instruments for diagnosing and evaluating orbital illnesses have become ophthalmic imaging modalities,including ocular ultrasonography(B-scan),computed tomography(CT),and magnetic resonance imaging(MRI).One way to improve the precision and promptness of diagnosing orbital diseases is to standardize the functioning of widely used imaging equipment and define the radiological features of orbital *** programs are crucial for the care of patients with orbital disorders since they considerably reduce the number of misdiagnoses and missed diagnoses in these *** underlying concepts,operational techniques,and normal and pathological imaging findings associated with common diagnostic tools for orbital illnesses are all thoroughly reviewed in this *** objective is to improve primary healthcare settings’diagnostic competence in the field of orbital pathology and to standardize procedures for diagnosing orbital disorders.

关键词： orbital disease ultrasonography computed tomography magnetic resonance imaging standardized operation