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Blood-brain barrier pathology in cerebral small vessel disease

Neural Regeneration Research 2024年第6期19卷 1233-1240页

作者： Ruxue Jia Gemma Solé-Guardia Amanda J.Kiliaan Department of medical Imaging Anatomy Radboud University Medical Center Donders Institute for Brain Cognition & Behavior Center for Medical Neuroscience Preclinical Imaging Center PRIME Radboud Alzheimer Center

Cerebral small vessel disease is a neurological disease that affects the brain microvasculature and which is commonly observed among the elderly. Although at first it was considered innocuous, small vessel disease is nowadays regarded as one of the major vascular causes of dementia. Radiological signs of small vessel disease include small subcortical infarcts, white matter magnetic resonance imaging hyperintensities, lacunes, enlarged perivascular spaces, cerebral microbleeds, and brain atrophy; however, great heterogeneity in clinical symptoms is observed in small vessel disease patients. The pathophysiology of these lesions has been linked to multiple processes, such as hypoperfusion, defective cerebrovascular reactivity, and blood-brain barrier dysfunction. Notably, studies on small vessel disease suggest that blood-brain barrier dysfunction is among the earliest mechanisms in small vessel disease and might contribute to the development of the hallmarks of small vessel disease. Therefore, the purpose of this review is to provide a new foundation in the study of small vessel disease pathology. First, we discuss the main structural domains and functions of the blood-brain barrier. Secondly, we review the most recent evidence on blood-brain barrier dysfunction linked to small vessel disease. Finally, we conclude with a discussion on future perspectives and propose potential treatment targets and interventions.

关键词： blood-brain barrier dysfunction cerebral blood flow cerebral hypoperfusion endothelial dysfunction hypertension inflammation magnetic resonance imaging neurovascular unit oxidative stress small vessel disease tight junctions transcytosis

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A prognostic four-gene signature and a therapeutic strategy for hepatocellular carcinoma:Construction and analysis of a circRNA-mediated competing endogenous RNA network

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Hepatobiliary & Pancreatic Diseases international 2024年第3期23卷 272-287页

作者： Hai-Yan Zhang Jia-Jie Zhu Zong-Ming Liu Yu-Xuan Zhang Jia-Jia Chen Ke-Da Chen Zhejiang Chinese medical University Hangzhou 310053China Shulan international medical College Zhejiang Shuren UniversityHangzhou 310015China State Key Laboratory for Diagnosis and Treatment of Infectious Diseases National Clinical Research Center for Infectious DiseasesNational Medical Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310009China

Background:Hepatocellular carcinoma(HCC)has a poor long-term prognosis.The competition of circular RNAs(circRNAs)with endogenous RNA is a novel tool for predicting HCC prognosis.Based on the alterations of circRNA regulatory networks,the analysis of gene modules related to HCC is feasible.Methods:Multiple expression datasets and RNA element targeting prediction tools were used to construct a circRNA-microRNA-mRNA network in HCC.Gene function,pathway,and protein interaction analyses were performed for the differentially expressed genes(DEGs)in this regulatory network.In the proteinprotein interaction network,hub genes were identified and subjected to regression analysis,producing an optimized four-gene signature for prognostic risk stratification in HCC patients.Anti-HCC drugs were excavated by assessing the DEGs between the low-and high-risk groups.A circRNA-microRNA-hub gene subnetwork was constructed,in which three hallmark genes,KIF4A,CCNA2,and PBK,were subjected to functional enrichment analysis.Results:A four-gene signature(KIF4A,CCNA2,PBK,and ZWINT)that effectively estimated the overall survival and aided in prognostic risk assessment in the The Cancer Genome Atlas(TCGA)cohort and international Cancer Genome Consortium(ICGC)cohort was developed.CDK inhibitors,PI3K inhibitors,HDAC inhibitors,and EGFR inhibitors were predicted as four potential mechanisms of drug action(MOA)in high-risk HCC patients.Subsequent analysis has revealed that PBK,CCNA2,and KIF4A play a crucial role in regulating the tumor microenvironment by promoting immune cell invasion,regulating microsatellite instability(MSI),and exerting an impact on HCC progression.Conclusions:The present study highlights the role of the circRNA-related regulatory network,identifies a four-gene prognostic signature and biomarkers,and further identifies novel therapy for HCC.

关键词： Hepatocellular carcinoma circRNA-related ceRNA network Biomarker Least absolute shrinkage and selection operator Bioinformatics

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Magnetic resonance imaging-guided focused ultrasound thalamotomy launch with remote telemedicine international proctorship

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Chronic Diseases and Translational Medicine 2024年第1期10卷 40-50页

作者： Igor V.Buzaev Rezida M.Galimova Dinara I.Nabiullina Sergey N.Illarioshkin Naufal Sh.Zagidullin Shamil M.Safin Department of Surgery Bashkir State Medical UniversityUfaRussia Intelligent Neurosurgery Clinic Ltd.International Medical Center V.S.Buzaev memorialUfaRussia Directorate Research Center of NeurologyVolokolamskoye ShosseMoscowRussia

Background: COVID-19 limitations have hindered the implementation of new technologies by preventing proctors from coming to the site.We share our first experience of magnetic resonance imaging(MRI)-guided focused ultrasound(MRgFUS)treatment with an international remote online proctorship,and develop and evaluate the methodology of remote MRgFUS proctorship.Methods: This single-center,nonrandomized controlled prospective study included 94 patients:27 with essential tremor(ET)and 67 with tremor-dominant Parkinson's disease(PD).The coming of proctors was impossible,so we arranged for the remote participation of proctors from the United Kingdom,Spain,and Israel.A total of 38 patients(40.4%)received telemedicine-proctored treatment(proctor group)and 56 received their treatment independently(solo group).We used the Clinical Rating Scale for Tremor(CRST)for ET patients and the Unified Parkinson's Disease Rating Scale(UPDRS)Part III for PD patients.Results: In patients with ET,success rates were 81.8%(proctor group)and 100%(solo group)(p=0.22).CRST reduction on the treated side was 71.43%[65.83%;80.56%](proctor group)versus 60.87%[53.99;79.58](solo group)(p=0.19).None of the patients showed worsening of tremors within 1 year.In patients with PD,the success rates were 92.6%(proctor group)and 100%(solo group)(p=0.08).The UPDRS Part III improvement was 30.1%(proctor group)versus 39.9%(solo group)(p=0.003).The 1-year recurrence rate was 40%(proctor group)and 17.5%(solo group)(p=0.04).No complications were observed at 6 months.Conclusions: We developed a feasible and safe methodology for telemedicine remote online-proctored MRgFUS treatment.No significant difference was observed between the solo and developed remote proctor protocols in terms of complication rate,effect,and long-term results;however,UPDRS Part III improvement was better in the PD solo group.This study demonstrated that the MRgFUS international proctorship can be performed successfully remotely.

关键词： essential tremor MRgFUS Parkinson's disease proctor telemedicine

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Latest assessment methods for mitochondrial homeostasis in cognitive diseases

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Neural Regeneration Research 2024年第4期19卷 754-768页

作者： Wei You Yue Li Kaixi Liu Xinning Mi Yitong Li Xiangyang Guo Zhengqian Li Department of Anesthesiology Peking University Third Hospital Peking University Third Clinical medical College Beijing center of Quality Control and Improvement on Clinical Anesthesia Anesthesia and Perioperative Medicine Branch of China international Exchange and Promotive Association for medical and Health Care(CPAM)

Mitochondria play an essential role in neural function,such as supporting normal energy metabolism,regulating reactive oxygen species,buffering physiological calcium loads,and maintaining the balance of morphology,subcellular distribution,and overall health through mitochondrial dynamics.Given the recent technological advances in the assessment of mitochondrial structure and functions,mitochondrial dysfunction has been regarded as the early and key pathophysiological mechanism of cognitive disorders such as Alzheimer’s disease,Parkinson’s disease,Huntington’s disease,mild cognitive impairment,and postoperative cognitive dysfunction.This review will focus on the recent advances in mitochondrial medicine and research methodology in the field of cognitive sciences,from the perspectives of energy metabolism,oxidative stress,calcium homeostasis,and mitochondrial dynamics(including fission-fusion,transport,and mitophagy).

关键词： cognitive disorders mitochondrial dysfunction mitochondrial energy metabolism mitochondrial dynamics mitochondrial transport mitophagy mitochondrial biogenesis oxidative stress calcium homeostasis

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Emergency department management of acute agitation in the reproductive age female and pregnancy

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World Journal of Emergency Medicine 2024年第2期15卷 83-90页

作者： Ariella Gartenberg Kayla Levine Alexander Petrie Department of Emergency Medicine Jacobi Medical Center and Montefiore Medical CenterNY 10461USA Department of Psychiatry and Behavioral Sciences Albert Einstein College of Medicine and Montefiore Medical CenterNY 10461USA Department of Emergency Medicine Jacobi Medical Center and North Central Bronx HospitalNY 10461USA

BACKGROUND:Agitation is a common presentation within emergent departments(EDs).Agitation during pregnancy should be treated as an obstetric emergency,as the distress may jeopardize both the patient and fetus.The safety of psychotropic medications in the reproductive age female has not been well established.This review aimed to explore a summary of general agitation recommendations with an emphasis on ED management of agitation during pregnancy.METHODS:A literature review was conducted to explore the pathophysiology of acute agitation and devise a preferred treatment plan for ED management of acute agitation in the reproductive age or pregnant female.RESULTS:While nonpharmacological management is preferred,ED visits for agitation often require medical management.Medication should be selected based on the etiology of agitation and the clinical setting to avoid major adverse effects.Adverse effects are common in pregnant females.For mild to moderate agitation in pregnancy,diphenhydramine is an effective sedating agent with minimal adverse effects.In moderate to severe agitation,high-potency typical psychotropics are preferred due to their neutral effects on hemodynamics.Haloperidol has become the most frequently utilized psychotropic for agitation during pregnancy.Second generation psychotropics are often utilized as second-line therapy,including risperidone.Benzodiazepines and ketamine have demonstrated adverse fetal outcomes.CONCLUSION:While randomized control studies cannot be ethically conducted on pregnant patients requiring sedation,animal models and epidemiologic studies have demonstrated the effects of psychotropic medication exposure in utero.As the fetal risk associated with multiple doses of psychotropic medications remains unknown,weighing the risks and benefits of each agent,while utilizing the lowest effective dose remains critical in the treatment of acute agitation within the EDs.

关键词： Agitation Pregnancy Haloperidol Ketamine Benzodiazepines

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Symmetry transformation of nonlinear optical current of tilted Weyl nodes and application to ferromagnetic MnBi_(2)Te_(4)

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Chinese Physics B 2024年第4期33卷 160-171页

作者：卢倬成冯济 international center for Quantum Materials School of PhysicsPeking UniversityBeijing 100871China

A Weyl node is characterized by its chirality and tilt.We develop a theory of how nth-order nonlinear optical conductivity behaves under transformations of anisotropic tensor and tilt, which clarifies how chirality-dependent and-independent parts of optical conductivity transform under the reversal of tilt and chirality.Built on this theory, we propose ferromagnetic Mn Bi2Te4as a magnetoelectrically regulated, terahertz optical device, by magnetoelectrically switching the chiralitydependent and-independent DC photocurrents.These results are useful for creating nonlinear optical devices based on the topological Weyl semimetals.

关键词： nonlinear optical response topological Weyl semimetals chiral anomaly

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CircPTEN-MT from PTEN regulates mitochondrial energy metabolism

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Journal of Genetics and Genomics 2024年第5期51卷 531-542页

作者： Danhui Ruan Jiancheng Xu Yang Liu Juan Luo Xuyang Zhao Yuhua Li Guangxi Wang Jiawen Feng Hui Liang Yue Yin Jianyuan Luo Yuxin Yin Institute of Systems Biomedicine Department of PathologySchool of Basic Medical SciencesBeijing Key Laboratory of Tumor Systems BiologyPeking University International Cancer InstitutePeking-Tsinghua Center of Life SciencesPeking University Health Science CenterBeijing 100191China Institute of Precision Medicine Peking University Shenzhen HospitalShenzhenGuangdong 518036China Department of Pharmacology School of Basic Medical SciencesPeking University Health Science CenterBeijing 100191China Department of medical Genetics Center for Medical GeneticsSchool of Basic Medical SciencesPeking University Health Science CenterBeijing 100191China Soochow University Cancer Institute SuzhouJiangsu 215127China

Phosphatase and tensin homolog(PTEN)is a multifunctional gene involved in a variety of physiological and pathological processes.Circular RNAs(circRNAs)are generated from back-splicing events during mRNA processing and participate in cell biological processes through binding to RNAs or proteins.However,PTEN-related circRNAs are largely unknown.Here,we report that circPTEN-mitochondria(MT)(hsa_circ_0002934)is a circular RNA encoded by exons 3,4,and 5 of PTEN and is a critical regulator of mitochondrial energy metabolism.CircPTEN-MT is localized to mitochondria and physically associated with leucine-rich pentatricopeptide repeat-containing protein(LRPPRC),which regulates posttranscriptional gene expression in mitochondria.Knocking down circPTEN-MT reduces the interaction of LRPPRC and steroid receptor RNA activator(SRA)stem-loop interacting RNA binding protein(SLIRP)and inhibits the polyadenylation of mitochondrial mRNA,which decreases the mRNA level of the mitochondrial complex I subunit and reduces mitochondrial membrane potential and adenosine triphosphate production.Our data demonstrate that circPTEN-MT is an important regulator of cellular energy metabolism.This study expands our understanding of the role of PTEN,which produces both linear and circular RNAs with different and independent functions.

关键词： Circular RNA LRPPRC Mitochondrial energy metabolism mtDNApost-transcriptional regulation

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Progress in the generation of spinal cord organoids over the past decade and future perspectives

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Neural Regeneration Research 2024年第5期19卷 1013-1019页

作者： Gang Zhou Siyuan Pang Yongning Li Jun Gao Department of Neurosurgery Peking Union Medical College HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijingChina Department of international medical Service Peking Union Medical College HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijingChina

Spinal cord organoids are three-dimensional tissues derived from stem cells that recapitulate the primary morphological and functional characteristics of the spinal cord in vivo.As emerging bioengineering methods have led to the optimization of cell culture protocols,spinal cord organoids technology has made remarkable advancements in the past decade.Our literature search found that current spinal cord organoids do not only dynamically simulate neural tube formation but also exhibit diverse cytoarchitecture along the dorsal-ventral and rostral-caudal axes.Moreover,fused organoids that integrate motor neurons and other regionally specific organoids exhibit intricate neural circuits that allows for functional assessment.These qualities make spinal cord organoids valuable tools for disease modeling,drug screening,and tissue regeneration.By utilizing this emergent technology,researchers have made significant progress in investigating the pathogenesis and potential therapeutic targets of spinal cord diseases.However,at present,spinal cord organoid technology remains in its infancy and has not been widely applied in translational medicine.Establishment of the next generation of spinal cord organoids will depend on good manufacturing practice standards and needs to focus on diverse cell phenotypes and electrophysiological functionality evaluation.

关键词： development organoid-on-a-chip pluripotent stem cells progress spinal cord diseases spinal cord organoids vascularization

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RARRES2 regulates lipid metabolic reprogramming to mediate the development of brain metastasis in triple negative breast cancer

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Military medical Research 2024年第1期11卷 34-49页

作者： Yi-Qun Li Fang-Zhou Sun Chun-Xiao Li Hong-Nan Mo Yan-Tong Zhou Dan Lv Jing-Tong Zhai Hai-Li Qian Fei Ma Department of medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China State Key Laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

Background Triple negative breast cancer(TNBC),the most aggressive subtype of breast cancer,is characterized by a high incidence of brain metastasis(BrM)and a poor prognosis.As the most lethal form of breast cancer,BrM remains a major clinical challenge due to its rising incidence and lack of effective treatment strategies.Recent evidence suggested a potential role of lipid metabolic reprogramming in breast cancer brain metastasis(BCBrM),but the underlying mechanisms are far from being fully elucidated.Methods Through analysis of BCBrM transcriptome data from mice and patients,and immunohistochemical validation on patient tissues,we identified and verified the specific down-regulation of retinoic acid receptor responder 2(RARRES2),a multifunctional adipokine and chemokine,in BrM of TNBC.We investigated the effect of aberrant RARRES2 expression of BrM in both in vitro and in vivo studies.Key signaling pathway components were evaluated using multi-omics approaches.Lipidomics were performed to elucidate the regulation of lipid metabolic reprogramming of RARRES2.Results We found that downregulation of RARRES2 is specifically associated with BCBrM,and that RARRES2 deficiency promoted BCBrM through lipid metabolic reprogramming.Mechanistically,reduced expression of RARRES2 in brain metastatic potential TNBC cells resulted in increased levels of glycerophospholipid and decreased levels of triacylglycerols by regulating phosphatase and tensin homologue(PTEN)-mammalian target of rapamycin(mTOR)-sterol regulatory element-binding protein 1(SREBP1)signaling pathway to facilitate the survival of breast cancer cells in the unique brain microenvironment.Conclusions Our work uncovers an essential role of RARRES2 in linking lipid metabolic reprogramming and the development of BrM.RARRES2-dependent metabolic functions may serve as potential biomarkers or therapeutic targets for BCBrM.

关键词： RARRES2 Lipid metabolic reprogramming Brain metastasis(BrM) Breast cancer

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Exploration of pathogenic microorganism within the small intestine of necrotizing enterocolitis

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World Journal of Pediatrics 2024年第2期20卷 165-172页

作者： Yan Wang Kun Jiang Qiao Xia Xia Kang Shan Wang Ji-Hong Yu Wen-Feng Ni Xiao-Qin Qi Ying-Na Zhang Jin-Bao Han Gang Liu Lei Hou Zhi-Chun Feng Liu-Ming Huang Clinical Biobank center Medical Innovation Research Division of ChinesePLA General HospitalBeijingChina Institute of Basic medical Sciences Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Senior Department of Pediatrics The Seventh Medical Center of PLA General HospitalBeijing 100700China Department of Neurology The First Medical CenterChinese PLA General HospitalBeijing 100853China Department of Emergency center National Center for Children's HealthBeijing Children's HospitalCapital Medical UniversityBeijing 100045China

Background Necrotizing enterocolitis(NEC)is the most common severe gastrointestinal emergency in neonates.We designed this study to identify the pathogenic microorganisms of NEC in the microbiota of the small intestine of neonates.Methods Using the 16S ribosomal DNA(rDNA)sequencing method,we compared and analyzed the structure and diversity of microbiotas in the intestinal feces of different groups of neonates:patients undergoing jejunostomy to treat NEC(NP group),neonates undergoing jejunostomy to treat other conditions(NN group),and neonates with NEC undergoing conservative treatment(NC group).We took intestinal feces and saliva samples from patients at different time points.Results The beta diversities of the NP,NN,and NC groups were all similar.When comparing the beta diversities between different time points in the NP group,we found similar beta diversities at time points El to E3 but significant differences between the E2-E3 and E4 time points:the abundances of Klebsiella and Enterococcus(Proteobacteria)were higher at the E1-E3 time points;the abundance of Escherichia-Shigella(Proteobacteria)increased at the E2 time point,and the abundance of Klebsiella decreased significantly,whereas that of Streptococcus increased significantly at the E4 time point.Conclusions Our results suggest that the pathological changes of intestinal necrosis in the small intestine of infants with NEC are not directly caused by excessive proliferation of pathogenic bacteria in the small intestine.The sources of microbiota in the small intestine of neonates,especially in premature infants,may be affected by multiple factors.

关键词： Microbiota Necrotizing enterocolitis-Small intestine 16S rDNA

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