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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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Syrosingopine,an anti-hypertensive drug and lactate transporter(MCT1/4)inhibitor,activates hepatic stellate cells and exacerbates liver fibrosis in a mouse model

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Genes & Diseases 2024年第4期11卷 28-30页

作者： Meichun Guo Yannian Gou Xiangyu Dong Jiamin Zhong Aohua Li Ailing Hao Tongchuan He Jiaming Fan Ministry of Education Key Laboratory of diagnostic Medicine and the School of Laboratory Diagnostic MedicineChongqing Medical UniversityChongqing 400016China Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA

Syrosingopine is an anti-hypertensive drug and can cause high intracellular lactate levels and end-product inhibition of lactate dehydrogenase by inhibiting the lactate transporters MCT1 and MCT4.Previous studies have shown that syrosingopine plays an essential role in the process of glycolytic blockade,ATP depletion,and cell death in cancer due to high intracellular levels of lactate.

关键词： hypertensive MCT1 drug

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Strain-dependent alpha-synuclein spreading in Parkinson's disease and multiple system atrophy

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Neural Regeneration Research 2024年第12期19卷 2581-2582页

作者： Shuyu Zhang Paul Lingor Department of Neurology School of MedicineUniversity Hospital rechts der IsarTechnical University of MunichMunichGermany Department of Neurology University Medical Center GöttingenGöttingenGermany center for Biostructural imaging of Neurodegeneration University Medical Center GöttingenGöttingenGermany

Parkinson's disease(PD) and atypical Parkinsonian syndromes,such as multiple system atrophy(MSA) and Dementia with Lewy bodies,are neurodegenerative movement disorders characterized by the accumulation of alphasynuclein(a-syn) aggregates.These a-syn aggregates propagate throughout the brain in a prion-like manner,where pathological a-syn recruits endogenous a-syn to form insoluble aggregates.Oligomeric forms representing intermediates on the way to insoluble aggregates result in the most pronounced neurotoxic effects.

关键词： atrophy endogenous atypical

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Development and validation of a preoperative prediction model for all-cause mortality in patients following abdominal aortic aneurysm repair

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中华医学杂志(英文版) 2024年第10期137卷 1255-1257页

作者： Li Tan Li Guangxiao Wu Yijun Yang Chao Yang Jun Sun Liping Ma Chunyan Department of Cardiovascular Ultrasound The First Hospital of China Medical University Shenyang Liaoning China Clinical medical Research center of imaging in Liaoning Province The First Hospital of China Medical University Shenyang Liaoning China Department of medical Record Management center The First Hospital of China Medical University Shenyang Liaoning China Tumor Etiology and Screening Department of Cancer Institute and General Surgery The First Hospital of China Medical University Shenyang Liaoning China Trauma center and Department of Burns The First Hospital of China Medical University Shenyang Liaoning China

Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease. Surgical intervention is typically recommended when the maximum AAA diameter reaches a threshold of 5.5ficm for men and 5.0ficm for women, or when an AAA experiences a rapid expansion of greater than 1.0ficm/year.[1] Survival after AAA repair is influenced by various factors, and the identification of independent prognostic factors and the development of accurate prediction models are crucial for optimal treatment planning, counseling, and postoperative follow-up. Although several scoring systems with varying degrees of accuracy have been developed to predict the risk of mortality after intervention for patients with ruptured AAA, conflicting results regarding their performance have been published.[2,3] Ideally, prediction models should be user-friendly and widely applicable, providing quick and reliable estimates of outcomes based on only a few readily available preoperative parameters. Unfortunately, the number of clinical models assisting clinicians in estimating the long-term mortality of general AAA patients after aneurysm repair is limited, and there is a lack of scores focusing on the Chinese population. Therefore, the objectives of the present study were to explore potential biomarkers affecting the long-term mortality risk of patients who underwent AAA repair and to establish an easy-to-use and practical preoperative risk prediction model for all-cause mortality after AAA repair in Chinese population. This model might help stratify AAA patients into different groups according to their predicted life expectancy, informing decision-making, and implementing medical intervention in clinical trials.

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Ambroxol,the cough expectorant with neuroprotective effects

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Neural Regeneration Research 2024年第11期19卷 2345-2346页

作者： Kristin Patzwaldt Salvador Castaneda-Vega Werner Siemens imaging center Department of Preclinical Imaging and RadiopharmacyEberhard Karls University TuebingenTuebingenGermany Department of Nuclear Medicine and Clinical Molecular imaging University Clinic TuebingenTuebingenGermany

Ambroxol hydrochloride(2-amino-3,5-dibromo-N-methylbenzylamine hydrochloride)has been used as a mucolytic agent in the treatment of respiratory diseases since the late 1970s.Its effects on mucus membranes such as mucus disruption,increased mucus production,and low toxicity profile were addressed in its original German patent in 1966.These first described properties have kept Ambroxol available worldwide and over the counter in the pharmaceutical market to this day.

关键词： protective agent German

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Preoperative prediction of lymphovascular and perineural invasion in gastric cancer using spectral computed tomography imaging and machine learning

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World Journal of Gastroenterology 2024年第6期30卷 542-555页

作者： Hui-Ting Ge Jian-Wu Chen Li-Li Wang Tian-Xiu Zou Bin Zheng Yuan-Fen Liu Yun-Jing Xue Wei-Wen Lin Department of Radiology Fujian Medical University Union HospitalFuzhou 350001Fujian ProvinceChina Fujian Key Laboratory of Intelligent imaging and Precision Radiotherapy for Tumors Fujian Medical UniversityFuzhou 350001Fujian ProvinceChina Digestive Hematological and Breast MalignanciesClinical Research Center for Radiology and Radiotherapy of Fujian ProvinceFuzhou 350001Fujian ProvinceChina Department of Radiation Oncology Fujian Medical University Union HospitalFuzhou 350001Fujian ProvinceChina Department of diagnostic Radiology Fujian Medical University Union HospitalFuzhou 350001Fujian ProvinceChina School of Electrical and Computer Engineering University of OklahomaOklahomaOK 73019United States

BACKGROUND Lymphovascular invasion(LVI)and perineural invasion(PNI)are important prognostic factors for gastric cancer(GC)that indicate an increased risk of metastasis and poor outcomes.Accurate preoperative prediction of LVI/PNI status could help clinicians identify high-risk patients and guide treatment deci-sions.However,prior models using conventional computed tomography(CT)images to predict LVI or PNI separately have had limited accuracy.Spectral CT provides quantitative enhancement parameters that may better capture tumor invasion.We hypothesized that a predictive model combining clinical and spectral CT parameters would accurately preoperatively predict LVI/PNI status in GC patients.AIM To develop and test a machine learning model that fuses spectral CT parameters and clinical indicators to predict LVI/PNI status accurately.METHODS This study used a retrospective dataset involving 257 GC patients(training cohort,n=172;validation cohort,n=85).First,several clinical indicators,including serum tumor markers,CT-TN stages and CT-detected extramural vein invasion(CT-EMVI),were extracted,as were quantitative spectral CT parameters from the delineated tumor regions.Next,a two-step feature selection approach using correlation-based methods and information gain ranking inside a 10-fold cross-validation loop was utilized to select informative clinical and spectral CT parameters.A logistic regression(LR)-based nomogram model was subsequently constructed to predict LVI/PNI status,and its performance was evaluated using the area under the receiver operating characteristic curve(AUC).RESULTS In both the training and validation cohorts,CT T3-4 stage,CT-N positive status,and CT-EMVI positive status are more prevalent in the LVI/PNI-positive group and these differences are statistically significant(P<0.05).LR analysis of the training group showed preoperative CT-T stage,CT-EMVI,single-energy CT values of 70 keV of venous phase(VP-70 keV),and the ratio of standardized iodine concentration of equilibrium phase(EP-NIC)were ind

关键词： Spectral computed tomography Gastric cancer Lymphovascular invasion Perineural invasion

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Adaptive ultra-hypofractionated whole-pelvic radiotherapy in high-risk and very high-risk prostate cancer on 1.5-Tesla MR-Linac:Estimated delivered dose and early toxicity results

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Chronic Diseases and Translational Medicine 2024年第1期10卷 51-61页

作者： Linrui Gao Ran Wei Shirui Qin Yuan Tian Wenlong Xia Yongwen Song Shulian Wang Hui Fang Yu Tang Hao Jing Yueping Liu Yuan Tang Shunan Qi Bo Chen Yexiong Li Nianzeng Xing Ningning Lu Department of Radiation Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina GCP center/Clinical Research center National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Department of Urology State Key Laboratory of Molecular OncologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

Background: Magnetic resonance(MR)-guided ultra-hypofractionated radiotherapy with whole-pelvic irradiation(UHF-WPRT)is a novel approach to radiotherapy for patients with high-risk(HR)and very high-risk(VHR)prostate cancer(PCa).However,the inherent complexity of adaptive UHF-WPRT might inevitably result in longer on-couch time.We aimed to estimate the delivered dose,study the feasibility and safety of adaptive UHF-WPRT on a 1.5-Tesla MR-Linac.Methods: Ten patients with clinical stage T3a-4N0-1M0-1c PCa,who consecutively received UHF-WPRT,were enrolled prospectively.The contours of the target and organ-at-risks on the position verification-MR(PV-MR),beam-on 3D-MR(Bn-MR),and post-MR(after radiotherapy delivery)were derived from the pre-MR data by deformable image registration.The physician then manually adjusted them,and dose recalculation was performed accordingly.GraphPad Prism 9(GraphPad Prism Software Inc.)was utilized for conducting statistical analyses.Results: In total,we collected 188 MR scans(50 pre-MR,50 PV-MR,44 Bn-MR,and 44 post-MR scans).With median 59 min,the mean prostate clinical target volume(CTV)-V_(100%)was 98.59%±2.74%,and the mean pelvic CTVp-V_(100%)relative percentages of all scans was 99.60%±1.18%.The median V29 Gy change in the rectal wall was−2%(−18%to 20%).With a median follow-up of 9 months,no patient had acute Common Terminology Criteria for Adverse Events(CTCAE)grade 2 or more severe genitourinary(GU)or gastrointestinal(GI)toxicities(0%).Conclusion: UHF-RT to the prostate and the whole pelvis with concomitant boost to positive nodes using an Adapt-To-Shape(ATS)workflow was technically feasible for patients with HR and VHR PCa,presenting only mild GU and GI toxicities.The estimated target dose during the beam-on phase was clinically acceptable based on the 3D-MR-based dosimetry analysis.Clinical trial registration Chinese Clinical Trial Registry ChiCTR2000033382.

关键词： dosimetry hypofractionation magnetic resonance imaging prostate cancer radiation dose radiotherapy

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LDL-C rebound after long-term evolocumab treatment and intravascular imaging evidence in a familial hypercholesterolemia patient with early-onset myocardial infarction

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Chronic Diseases and Translational Medicine 2024年第1期10卷 69-74页

作者： Zhifan Li Shuang Zhang Zheng Yin Wenjia Zhang Yonggang Sui Jianjun Li Kefei Dou Jie Qian Naqiong Wu Cardiometabolic center National Center for Cardiovascular DiseasesFuwai HospitalChinese Academy of Medical Science and Peking Union Medical CollegeBeijingChina

Patients with familial hypercholesterolemia(FH)have elevated low-density lipoprotein cholesterol(LDL-C)levels and are at high risk of premature cardiovascular disease.1 Heterozygous FH(HeFH)is one of the commonest genetic disorders,and is more frequent among those with ischemic heart disease(IHD),atherosclerotic cardiovascular disease(ASCVD)and premature IHD.

关键词： cardiovascular familial elevated

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Multimodal cardiac imaging assisted tumor characterization and surgical planning of a patient with rare primary cardiac paraganglioma

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Journal of Geriatric Cardiology 2024年第2期21卷 246-250页

作者： Shu-Yu MENG Li-Qun WANG Hao-Dan DANG Lin ZHANG Sheng-Li JIANG Bo-Han LIU Department of Ultrasound Diagnosis the First Medical CenterChinese PLA General HospitalBeijingChina Department of Nuclear Medicine the First Medical CenterChinese PLA General HospitalBeijingChina Department of Pathology the First Medical CenterChinese PLA General HospitalBeijingChina Department of Cardiovascular Surgery the First Medical CenterChinese PLA General HospitalBeijingChina

Paragangliomas,also known as pheochromocytomas(1–9 cases per million),arise in the paraganglia.[1]Pheochromocytomas occur in the adrenal glands,while paragangliomas occur elsewhere.[2]Paragangliomas originate from paraganglion cells,which are derived from the neural ectoderm of the nerves and migrate along both sides of the median axis from the base of the skull to the pelvis during embryonic development.

关键词： glioma cardiac nerves

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Exploration of potential biomarkers and therapeutic targets for trauma-related acute kidney injury

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Chinese Journal of Traumatology 2024年第2期27卷 97-106页

作者： Peng Qi Meng-Jie Huang Wei Wu Xue-Wen Ren Yong-Zhi Zhai Chen Qiu Hai-Yan Zhu Department of Emergency First Medical Center of Chinese PLA General HospitalBeijing100853China Department of Nephrology.First medical center of Chinese PLA General Hospital Beijing100853China Department of Anesthesiology.First medical center of Chinese PLA General Hospital Beijing100853China Department of Orthopedics Fourth Medical Center of Chinese PLA General HospitalBeijing100853China

Purpose:Acute kidney injury(AKI)is one of the most common functional injuries observed in trauma patients.However,certain trauma medications may exacerbate renal injury.Therefore,the early detection of trauma-related AKI holds paramount importance in improving trauma prognosis.Methods:Qualified datasets were selected from public databases,and common differentially expressed genes related to trauma-induced AKI and hub genes were identified through enrichment analysis and the establishment of protein-protein interaction(PPI)networks.Additionally,the specificity of these hub genes was investigated using the sepsis dataset and conducted a comprehensive literature review to assess their plausibility.The raw data from both datasets were downloaded using R software(version 4.2.1)and processed with the"affy"package19 for correction and normalization.Results:Our analysis revealed 585 upregulated and 629 downregulated differentially expressed genes in the AKI dataset,along with 586 upregulated and 948 downregulated differentially expressed genes in the trauma dataset.Concurrently,the establishment of the PPI network and subsequent topological analysis highlighted key hub genes,including CD44,CD163,TIMP metallopeptidase inhibitor 1,cytochrome b-245 beta chain,versican,membrane spanning 4-domains A4A,mitogen-activated protein kinase 14,and early growth response 1.Notably,their receiver operating characteristic curves displayed areas exceeding 75%,indicating good diagnostic performance.Moreover,our findings postulated a unique molecular mechanism underlying trauma-related AKI.Conclusion:This study presents an alternative strategy for the early diagnosis and treatment of trauma-related AKI,based on the identification of potential biomarkers and therapeutic targets.Additionally,this study provides theoretical references for elucidating the mechanisms of trauma-related AKI.

关键词： Trauma Acutekidney injury Bioinformatic analysis Differentially expressed genes Biomarker

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