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Global trends in diabetic eye disease research from 2012 to 2021

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Neural Regeneration Research 2024年第10期19卷 2310-2320页

作者： Yuan Yuan Shangli Ji Yali Song Zhaodi Che Lu Xiao Shibo Tang Jia Xiao Aier School of Ophthalmology Central South UniversityChangshaHunan ProvinceChina Changsha Aier Eye Hospital ChangshaHunan ProvinceChina Aier Eye institute ChangshaHunan ProvinceChina Department of metabolic and Bariatric Surgery The First Affiliated Hospital of Jinan UniversityGuangzhouGuangdong ProvinceChina

Diabetic eye disease refers to a group of eye complications that occur in diabetic patients and include diabetic retinopathy, diabetic macular edema, diabetic cataracts, and diabetic glaucoma. However, the global epidemiology of these conditions has not been well characterized. In this study, we collected information on diabetic eye disease-related research grants from seven representative countries––the United States, China, Japan, the United Kingdom, Spain, Germany, and France––by searching for all global diabetic eye disease journal articles in the Web of Science and Pub Med databases, all global registered clinical trials in the Clinical Trials database, and new drugs approved by the United States, China, Japan, and EU agencies from 2012 to 2021. During this time period, diabetic retinopathy accounted for the vast majority(89.53%) of the 2288 government research grants that were funded to investigate diabetic eye disease, followed by diabetic macular edema(9.27%). The United States granted the most research funding for diabetic eye disease out of the seven countries assessed. The research objectives of grants focusing on diabetic retinopathy and diabetic macular edema differed by country. Additionally, the United States was dominant in terms of research output, publishing 17.53% of global papers about diabetic eye disease and receiving 22.58% of total citations. The United States and the United Kingdom led international collaborations in research into diabetic eye disease. Of the 415 clinical trials that we identified, diabetic macular edema was the major disease that was targeted for drug development(58.19%). Approximately half of the trials(49.13%) pertained to angiogenesis. However, few drugs were approved for ophthalmic(40 out of 1830;2.19%) and diabetic eye disease(3 out of 1830;0.02%) applications. Our findings show that basic and translational research related to diabetic eye disease in the past decade has not been highly active, and has yielded few new treatment methods and newly approved drugs.

关键词： clinical trials diabetic cataracts diabetic eye disease diabetic glaucoma diabetic macular edema diabetic retinopathy drug development global research publication research grant

Diarrhea induced by insufficient fat absorption in weaned piglets:Causes and nutrition regulation

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Animal Nutrition 2024年第1期16卷 299-305页

作者： Yuying Li Pengjun Shi Kang Yao Qian Lin Mansheng Wang Zhenping Hou Wenjie Tang Hui Diao institute of Bast Fiber Crops Chinese Academy of Agricultural Sciences institute of Subtropical Agriculture Chinese Academy of Sciences Hunan Province Key Laboratory of Animal Nutritional Physiology and Metabolic Process Animal Breeding and Genetics Key Laboratory of Sichuan Province Livestock and Poultry Biological Products Key Laboratory of Sichuan Province Sichuan Animal Science Academy Sichuan Animtech Feed Co. Ltd

Fat is one of the three macronutrients and a significant energy source for piglets. It plays a positive role in maintaining intestinal health and improving production performance. During the weaning period,physiological, stress and diet-related factors influence the absorption of fat in piglets, leading to damage to the intestinal barrier, diarrhea and even death. Signaling pathways, such as fatty acid translocase(CD36), pregnane X receptor(PXR), and AMP-dependent protein kinase(AMPK), are responsible for regulating intestinal fat uptake and maintaining intestinal barrier function. Therefore, this review mainly elaborates on the reasons for diarrhea induced by insufficient fat absorption and related signaling pathways in weaned-piglets, with an emphasis on the intestinal fat absorption disorder. Moreover, we focus on introducing nutritional strategies that can promote intestinal fat absorption in piglets with insufficient fat absorption-related diarrhea, such as lipase, amino acids, and probiotics.

关键词： Weaned piglet Diarrhea Fat absorption Nutrient regulation

PML nuclear bodies:new players in familial amyotrophic lateral sclerosis-frontotemporal dementia?

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Neural Regeneration Research 2024年第9期19卷 1875-1876页

作者： Anand Goswami Serena Carra institute of Neuropathology RWTH Aachen University HospitalAachenGermany Department of Neurology Eleanor and Lou Gehrig ALS CenterColumbia UniversityNew YorkNYUSA Department of Biomedical Metabolic and Neural SciencesUniversity of Modena and Reggio EmiliaModenaItaly

Amyotrophi c lateral s c lerosis(ALS)and frontotemporal dementia(FTD)are two closely related disorders with overlapping clinical,genetic,and neuropathological features,forming a continuous disease spectrum(Ling et al.,2013).The major pathological hallmark of ALS and FTD are the depletion from the nucleus of the RNA-binding proteins TAR DNA‐binding protein 43(TDP-43)and FUsed in Sarcoma(FUS)and their abnormal accumulation in ubiquitin-positive cytoplasmic inclusions(Ling et al.,2013).

关键词： clinical familial

Screening for metabolic dysfunction-associated fatty liver disease:Time to discard the emperor’s clothes of normal liver enzymes?

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World Journal of Gastroenterology 2024年第22期30卷 2839-2842页

作者： Chen-Xiao Huang Xiao-Dong Zhou Calvin Q Pan Ming-Hua Zheng metabolic Dysfunction-Associated Fatty Liver disease Research Center Department of HepatologyThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhou 325000Zhejiang ProvinceChina Department of Cardiovascular Medicine The Key Laboratory of Cardiovascular Diseases of WenzhouThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhou 325000Zhejiang ProvinceChina Division of Gastroenterology and Hepatology Department of MedicineNew York University Langone HealthNew York University Grossman School of MedicineNew YorkNY 11355United States institute of Hepatology Wenzhou Medical UniversityKey Laboratory of Diagnosis and Treatment for the Development of Chronic Liver Disease in Zhejiang ProvinceWenzhou 325000Zhejiang ProvinceChina

metabolic dysfunction-associated fatty liver disease(MAFLD)is the most prevalent chronic liver condition worldwide.Current liver enzyme-based screening methods have limitations that may missed diagnoses and treatment delays.Regarding Chen et al,the risk of developing MAFLD remains elevated even when alanine aminotransferase levels fall within the normal range.Therefore,there is an urgent need for advanced diagnostic techniques and updated algorithms to enhance the accuracy of MAFLD diagnosis and enable early intervention.This paper proposes two potential screening methods for identifying individuals who may be at risk of developing MAFLD:Lowering these thresholds and promoting the use of noninvasive liver fibrosis scores.

关键词： metabolic dysfunction-associated fatty liver disease Non-alcoholic fatty liver disease Alanine aminotransferase Liver enzymes Screening Noninvasive liver fibrosis scores

LONP1 ameliorates liver injury and improves gluconeogenesis dysfunction in acute-on-chronic liver failure

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Chinese Medical Journal 2024年第2期137卷 190-199页

作者： Muchen Wu Jing Wu Kai Liu Minjie Jiang Fang Xie Xuehong Yin Jushan Wu Qinghua Meng Department of Liver disease Beijing You-An HospitalCapital Medical UniversityBeijing 100069China Beijing institute of Hepatology Beijing You-An HospitalCapital Medical UniversityBeijing 100069China Department of General Surgery Beijing You-An HospitalCapital Medical UniversityBeijing 100069China

Background:Acute-on-chronic liver failure(ACLF)is a severe liver disease with complex pathogenesis.Clinical hypoglycemia is common in patients with ACLF and often predicts a worse prognosis.Accumulating evidence suggests that glucose metabolic disturbance,especially gluconeogenesis dysfunction,plays a critical role in the disease progression of ACLF.Lon protease-1(LONP1)is a novel mediator of energy and glucose metabolism.However,whether gluconeogenesis is a potential mechanism through which LONP1 modulates ACLF remains unknown.Methods:In this study,we collected liver tissues from ACLF patients,established an ACLF mouse model with carbon tetrachloride(CCl 4),lipopolysaccharide(LPS),and D-galactose(D-gal),and constructed an in vitro hypoxia and hyperammonemia-triggered hepatocyte injury model.LONP1 overexpression and knockdown adenovirus were used to assess the protective effect of LONP1 on liver injury and gluconeogenesis regulation.Liver histopathology,biochemical index,mitochondrial morphology,cell viability and apoptosis,and the expression and activity of key gluconeogenic enzymes were detected to explore the underlying protective mechanisms of LONP1 in ACLF.Results:We found that LONP1 and the expressions of gluconeogenic enzymes were downregulated in clinical ACLF liver tissues.Furthermore,LONP1 overexpression remarkably attenuated liver injury,which was characterized by improved liver histopathological lesions and decreased serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in ACLF mice.Moreover,mitochondrial morphology was improved upon overexpression of LONP1.Meanwhile,the expression and activity of the key gluconeogenic enzymes were restored by LONP1 overexpression.Similarly,the hepatoprotective effect was also observed in the hepatocyte injury model,as evidenced by improved cell viability,reduced cell apoptosis,and improved gluconeogenesis level and activity,while LONP1 knockdown worsened liver injury and gluconeogenesis disorders.Conclusion:We demonstrated that gluconeogenesis dysfunc

关键词： Acute-on-chronic liver failure Lon protease-1 Gluconeogenesis disturbance Mitochondrial dysfunction Metabolism

Piezo1 expression in chondrocytes controls endochondral ossification and osteoarthritis development

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Bone Research 2024年第1期12卷 199-214页

作者： Laura J.Brylka Assil-Ramin Alimy Miriam E.A.Tschaffon-Müller Shan Jiang Tobias Malte Ballhause Anke Baranowsky Simon von Kroge Julian Delsmann Eva Pawlus Kian Eghbalian Klaus Püschel Astrid Schoppa Melanie Haffner-Luntzer David J.Beech Frank Timo Beil Michael Amling Johannes Keller Anita Ignatius Timur A.Yorgan Tim Rolvien Thorsten Schinke Department of Osteology and Biomechanics University Medical Center Hamburg-Eppendorf20246 HamburgGermany Department of Trauma and Orthopedic Surgery University Medical Center Hamburg-Eppendorf20246 HamburgGermany institute of Orthopedic Research and Biomechanics University Medical Center UlmBadenWürttemberg89081 UlmGermany Department Legal Medicine University Medical Center Hamburg-Eppendorf20246 HamburgGermany Leeds institute of Cardiovascular and metabolic Medicine School of MedicineUniversity of LeedsLS29JT LeedsUK

Piezo proteins are mechanically activated ion channels,which are required for mechanosensing functions in a variety of cell types.While we and others have previously demonstrated that the expression of Piezo1 in osteoblast lineage cells is essential for boneanabolic processes,there was only suggestive evidence indicating a role of Piezo1 and/or Piezo2 in cartilage.Here we addressed the question if and how chondrocyte expression of the mechanosensitive proteins Piezo1 or Piezo2 controls physiological endochondral ossification and pathological osteoarthritis(OA)development.Mice with chondrocyte-specific inactivation of Piezo1(Piezo1^(Col2a1Cre)),but not of Piezo2,developed a near absence of trabecular bone below the chondrogenic growth plate postnatally.Moreover,all Piezo1^(Col2a1Cre) animals displayed multiple fractures of rib bones at 7 days of age,which were located close to the growth plates.While skeletal growth was only mildly affected in these mice,OA pathologies were markedly less pronounced compared to littermate controls at 60 weeks of age.Likewise,when OA was induced by anterior cruciate ligament transection,only the chondrocyte inactivation of Piezo1,not of Piezo2,resulted in attenuated articular cartilage degeneration.Importantly,osteophyte formation and maturation were also reduced in Piezo1^(Col2a1Cre) mice.We further observed increased Piezo1 protein abundance in cartilaginous zones of human osteophytes.Finally,we identified Ptgs2 and Ccn2 as potentially relevant Piezo1 downstream genes in chondrocytes.Collectively,our data do not only demonstrate that Piezo1 is a critical regulator of physiological and pathological endochondral ossification processes,but also suggest that Piezo1 antagonists may be established as a novel approach to limit osteophyte formation in OA.

关键词： Piezo1 markedly ossification

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 microbiota.Methods Liquid chromatography-tandem mass spectrometry was used to determine ten hydroxyl metabolites of PAHs(OH-PAHs)in 36-month-old children.Subsequently,37 children were categorized into low-and high-exposure groups based on the sum of the ten OH-PAHs.Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was used to identify non-targeted metabolites in the urine samples.Furthermore,fecal flora abundance was assessed by 16S rRNA gene sequencing using Illumina MiSeq.Results The concentrations of 21 metabolites were significantly higher in the high exposure group than in the low exposure group(variable importance for projection>1,Pmetabolic homeostasis,particularly that of certain gut microbiota-derived metabolites.Further 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

FibroScan-aspartate transaminase:A superior non-invasive model for diagnosing high-risk metabolic dysfunction-associated steatohepatitis

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World Journal of Gastroenterology 2024年第18期30卷 2440-2453页

作者： Jing-Ya Yin Tian-Yuan Yang Bing-Qing Yang Chen-Xue Hou Jun-Nan Li Yue Li Qi Wang Center of Liver diseases Beijing Ditan HospitalCapital Medical UniversityBeijing 100015China Department of Pathology Beijing Ditan HospitalCapital Medical UniversityBeijing 100015China Beijing institute of infectious disease Beijing 100015China Beijing Key Laboratory of Emerging Infectious diseases Institute of Infectious DiseasesBeijing Ditan HospitalCapital Medical UniversityBeijing 100015China

BACKGROUND Non-alcoholic fatty liver disease(NAFLD)with hepatic histological NAFLD activity score≥4 and fibrosis stage F≥2 is regarded as“at risk”non-alcoholic steatohepatitis(NASH).Based on an international consensus,NAFLD and NASH were renamed as metabolic dysfunction-associated steatotic liver disease(MASLD)and metabolic dysfunction-associated steatohepatitis(MASH),respectively;hence,we introduced the term“high-risk MASH”.Diagnostic values of seven non-invasive models,including FibroScan-aspartate transaminase(FAST),fibrosis-4(FIB-4),aspartate transaminase to platelet ratio index(APRI),etc.for high-risk MASH have rarely been studied and compared in MASLD.AIM To assess the clinical value of seven non-invasive models as alternatives to liver biopsy for diagnosing high-risk MASH.METHODS A retrospective analysis was conducted on 309 patients diagnosed with NAFLD via liver biopsy at Beijing Ditan Hospital,between January 2012 and December 2020.After screening for MASLD and the exclusion criteria,279 patients wereincluded and categorized into high-risk and non-high-risk MASH groups.Utilizing threshold values of each model,sensitivity,specificity,positive predictive value(PPV),and negative predictive values(NPV),were calculated.Receiver operating characteristic curves were constructed to evaluate their diagnostic efficacy based on the area under the curve(AUROC).RESULTS MASLD diagnostic criteria were met by 99.4%patients with NAFLD.The MASLD population was analyzed in two cohorts:Overall population(279 patients)and the subgroup(117 patients)who underwent liver transient elastography(FibroScan).In the overall population,FIB-4 showed better diagnostic efficacy and higher PPV,with sensitivity,specificity,PPV,NPV,and AUROC of 26.9%,95.2%,73.5%,72.2%,and 0.75.APRI,Forns index,and aspartate transaminase to alanine transaminase ratio(ARR)showed moderate diagnostic efficacy,whereas S index and gamma-glutamyl transpeptidase to platelet ratio(GPR)were relatively weaker.In the subgroup,FAST had the highest diagnostic efficacy,i

关键词： metabolic dysfunction-associated steatotic liver disease High-risk metabolic dysfunction-associated steatohepatitis Non-invasive models Liver biopsy Diagnostic value

Deferred revascularization in diabetic patient according to combined invasive functional and intravascular imaging data:A case report

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World Journal of Clinical Cases 2024年第13期12卷 2269-2274页

作者： Arif Al Nooryani Wael Aboushokka Branko Beleslin Biljana Nedeljkovic-Beleslin Department of Cardiology Al Qassimi HospitalSharjah 1234United Arab Emirates Department of Cardiology Medical FacultyUniversity of BelgradeBelgrade 11000Serbia institute of Endocrinology Diabetes and Metabolic DisordersUniveristy Clinical Center of SerbiaBelgrade 11000Serbia Department of Internal Medicine/Endocrinology Medical facultyUniversity of BelgradeBelgrade 11000Serbia

BACKGROUND Invasive functional evaluation by fractional flow reserve(FFR)is considered as a gold standard for the evaluation of intermediate coronary stenosis.However,in patients with diabetes due to accelerated progression of atherosclerosis the outcome may be worse even in the presence of negative functional testing.CASE SUMMARY We present a case of 55-year-old male diabetic patient who was admitted for chest pain.Diagnostic coronary angiography disclosed 2 intermediate stenoses of the obtuse marginal branch with no evidence of restenosis on previously implanted stent.Patient undergone invasive functional testing of intermediate lesion with preserved FFR(0.88),low coronary flow reserve(1.2)and very high index of microvascular resistance(84).Due to discrepancy in invasive functional parameters,intravascular imaging with optical coherence tomography showed fibrotic stenoses without signs of thin-sup fibroatheroma.Because of the preserved FFR and no signs of vulnerable plaque,the interventional procedure was deferred and the patient continued with optimal medications.CONCLUSION Combined functional and anatomic imaging of intermediate coronary stenosis in diabetic patients represent comprehensive contemporary decision pathway in the management of the patients.

关键词： Fractional flow reserve Coronary flow reserve Index of microvascular resistance Optical coherence tomography Intermediate coronary stenosis Case report