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Type-B monoamine oxidase inhibitors in neurological diseases:clinical applications based on preclinical findings

Neural Regeneration Research 2024年第1期19卷 16-21页

作者： Marika Alborghetti Edoardo Bianchini Lanfranco De Carolis Silvia Galli Francesco E.Pontieri Domiziana Rinaldi Neurology unit NESMOS DepartmentFaculty of Medicine&PsychologySapienza-University of RomeSant’Andrea University HospitalRomeItaly Department of clinical and Behavioral Neurology IRCCS-Fondazione Santa LuciaRomeItaly

Type-B monoamine oxidase inhibitors,encompassing selegiline,rasagiline,and safinamide,are available to treat Parkinson's *** drugs ameliorate motor symptoms and improve motor fluctuation in the advanced stages of the *** is also evidence suppo rting the benefit of type-B monoamine oxidase inhibitors on non-motor symptoms of Parkinson's disease,such as mood deflection,cognitive impairment,sleep disturbances,and *** studies indicate that type-B monoamine oxidase inhibitors hold a strong neuroprotective potential in Parkinson's disease and other neurodegenerative diseases for reducing oxidative stress and stimulating the production and release of neurotrophic factors,particularly glial cell line-derived neurotrophic factor,which suppo rt dopaminergic ***,safinamide may interfere with neurodegenerative mechanisms,countera cting excessive glutamate overdrive in basal ganglia motor circuit and reducing death from *** to the dual mechanism of action,the new generation of type-B monoamine oxidase inhibitors,including safinamide,is gaining interest in other neurological pathologies,and many supporting preclinical studies are now *** potential fields of application concern epilepsy,Duchenne muscular dystrophy,multiple scle rosis,and above all,ischemic brain *** purpose of this review is to investigate the preclinical and clinical pharmacology of selegiline,rasagiline,and safinamide in Parkinson's disease and beyond,focusing on possible future therapeutic applications.

关键词： glial cell line-derived neurotrophic factor(GDNF) glutamate neurological disorders neuroprotection Parkinson's disease preclinical studies rasagiline safinamide selegiline type-B monoamine oxidase(MAO_(B))inhibitors

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clinical applications of metagenomics next-generation sequencing in infectious diseases

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第6期25卷 471-484页

作者： Ying LIU Yongjun MA Department of clinical Laboratory Affiliated Jinhua HospitalZhejiang University School of MedicineJinhua 321000China

Infectious diseases are a great threat to human *** and accurate detection of pathogens is important in the diagnosis and treatment of infectious *** next-generation sequencing(mNGS)is an unbiased and comprehensive approach for detecting all RNA and DNA in a *** the development of sequencing and bioinformatics technologies,mNGS is moving from research to clinical application,which opens a new avenue for pathogen *** studies have revealed good potential for the clinical application of mNGS in infectious diseases,especially in difficult-to-detect,rare,and novel ***,there are several hurdles in the clinical application of mNGS,such as:(1)lack of universal workflow validation and quality assurance;(2)insensitivity to high-host background and low-biomass samples;and(3)lack of standardized instructions for mass data analysis and report ***,a complete understanding of this new technology will help promote the clinical application of mNGS to infectious *** review briefly introduces the history of next-generation sequencing,mainstream sequencing platforms,and mNGS workflow,and discusses the clinical applications of mNGS to infectious diseases and its advantages and disadvantages.

关键词： Metagenomics next-generation sequencing(mNGS) Infectious disease Cerebrospinal fluid(CSF) Oxford Nanopore Technologies(ONT) Microbiome

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Comparison of clinical features and outcomes of proliferative,fibrotic,and mixed subtypes of IgG4-related disease:A retrospective cohort study

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Chinese Medical Journal 2024年第3期137卷 303-311页

作者： Linyi Peng Xinlu Zhang Jiaxin Zhou Jieqiong Li Zheng Liu Hui Lu Yu Peng Yunyun Fei Yan Zhao Xiaofeng Zeng Wen Zhang Department of Rheumatology and clinical Immunology Peking Union Medical College HospitalNational Clinical Research Center for Dermatologic and Immunologic DiseasesState Key Laboratory of Complex Severe and Rare DiseasesThe Ministry of Education Key LaboratoryBeijing 100730China Institute of clinical Medicine Peking Union Medical College Hospital(PUMCH)Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China

Background:Immunoglobulin G4-related disease(IgG4-RD)is a recently recognized immune-mediated disorder that can affect almost any organ in the human ***4-RD can be categorized into proliferative and fibrotic subtypes based on patients’clinicopathological *** study aimed to compare the clinical manifestations,laboratory findings,and treatment outcomes of IgG4-RD among different ***:We prospectively enrolled 622 patients with newly diagnosed IgG4-RD at Peking Union Medical College Hospital from March 2011 to August *** patients were divided into three groups according to their clinicopathological characteristics:proliferative,fibrotic,and mixed *** compared demographic features,clinical manifestations,organ involvement,laboratory tests,and treatment agents across three *** then assessed the differences in treatment outcomes among 448 patients receiving glucocorticoids alone or in combination with ***,risk factors of relapse were revealed by applying the univariate and multivariate Cox regression ***:We classified the 622 patients into three groups consisting of 470 proliferative patients,55 fibrotic patients,and 97 mixed patients,*** found that gender distribution,age,disease duration,and frequency of allergy history were significantly different among *** terms of organ involvement,submandibular and lacrimal glands were frequently involved in the proliferative subtype,while retroperitoneum was the most commonly involved site in both fibrotic subtype and mixed *** comparison of laboratory tests revealed that eosinophils(P=0.010),total IgE(P=0.006),high-sensitivity C-reactive protein(P<0.001),erythrocyte sedimentation rate(P<0.001),complement C4(P<0.001),IgG(P=0.001),IgG1(P<0.001),IgG4(P<0.001),and IgA(P<0.001),at baseline were significantly different among three *** with proliferative and mixed subtypes,the fibrotic subtype showed the

关键词： IgG4-related disease Proliferative subtype Fibrotic subtype clinical features Treatment outcome

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Role of mitochondrial dysfunction in kidney disease:Insights from the cGAS-STING signaling pathway

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Chinese Medical Journal 2024年第9期137卷 1044-1053页

作者： Lu Li Fei Liu Chunyue Feng Zhenjie Chen Nan Zhang Jianhua Mao Department of Nephrology Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhouZhejiang 310052China Department of Pediatric Intensive Care unit Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhouZhejiang 310052China

Over the past decade,mitochondrial dysfunction has been investigated as a key contributor to acute and chronic kidney ***,the precise molecular mechanisms linking mitochondrial damage to kidney disease remain *** recent insights into the cyclic guanosine monophosphate-adenosine monophosphate(GMP-AMP)synthetase(cGAS)-stimulator of interferon gene(STING)signaling pathway have revealed its involvement in many renal *** of these findings is that mitochondrial DNA(mtDNA)induces inflammatory responses via the cGAS-STING ***,we provide an overview of the mechanisms underlying mtDNA release following mitochondrial damage,focusing specifically on the association between mtDNA release-activated cGAS-STING signaling and the development of kidney ***,we summarize the latest findings of cGAS-STING signaling pathway in cell,with a particular emphasis on its downstream signaling related to kidney *** review intends to enhance our understanding of the intricate relationship among the cGAS-STING pathway,kidney diseases,and mitochondrial dysfunction.

关键词： Mitochondrial dysfunction Mitochondrial DNA cGAS-STING pathway Kidney diseases Chronic kidney disease

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Recent landscape and trends for industry-sponsored pediatric clinical trials in China from 2013 to 2022

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Pediatric Investigation 2024年第1期8卷 12-20页

作者： Chang Liu Yi Liu Ling Ou Yuenan Qi Jianmin Zhang Drug clinical Trial Institution Children’s HospitalCapital Institute of PediatricsBeijingChina

Importance:Pediatric medication is a challenging issue *** trials of medications for children and implementing measures to encourage innovation for addressing unmet medical and health needs are ***:To explore the recent landscape of pediatric clinical trials of new investigational drugs conducted by pharmaceutical enterprises in China from 2013 to 2022 to provide insight into pediatric drug development in the pharmaceutical industry and regulatory policy ***:We performed a cross-sectional observational investigation of pediatric clinical trials registered from January 1,2013,to December 31,2022,on the Registration and Information Disclosure Platform for Drug clinical Trials,the official registration platform established in 2013 for trials of new investigational drugs initiated by biopharmaceutical *** that included pediatric participants(under 18 years old)were retrieved,and their relevant characteristics were extracted and ***:In total,895 pediatric clinical trials were collected,accounting for 5.1%of the total registered clinical trials initiated prior to January 1,*** overall average annual growth rate for the number of pediatric clinical trials was 12%(Pclinical trials,studies of vaccines accounted for the largest proportion of trials(41.0%,367),followed by trials for rare diseases(17.2%,154).Furthermore,geographical distribution analysis revealed that the largest and smallest numbers of trials were conducted in North China(35.7%,320)and Northeast China(0.8%,7),***:The growth trends for industry-sponsored clinical trials involving children illust

关键词： Geographic distribution Pediatric clinical trials Pediatric medication Rare disease

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Quick and easy assessment of sarcopenia in cirrhosis: Can ultrasound be the solution?

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World Journal of Gastroenterology 2024年第17期30卷 2287-2293页

作者： Francesca Campani Tancredi Vincenzo Li Cavoli Umberto Arena Fabio Marra Erica Nicola Lynch Claudia Campani Department of Health Science University Hospital CareggiUniversity of FlorenceFlorence 50134Italy Internal Medicine and Liver unit University Hospital CareggiUniversity of FlorenceFlorence 50134Italy Department of Experimental and clinical Medicine University of FlorenceFlorence 50134Italy Gastroenterology Research unit Department of Experimental and Clinical Biomedical Sciences“Mario Serio”University of FlorenceFlorence 50134Italy Department of Medical Biotechnologies University of SienaSiena 53100Italy

Cirrhosis is frequently associated with sarcopenia,with reported rates of over 80%in patients with decompensated alcohol-related liver *** nega-tively impacts the prognosis of cirrhotic patients and affects the response to treatment of patients with hepatocellular carcinoma(HCC).For these reasons,identifying an easy-to-perform method to assess sarcopenia in is a key element in the optimization of care in this patient *** of muscle mass by computed tomography is considered the standard of care for the diagnosis of sarcopenia,but exposure to radiation and high costs limit its application in this setting,especially for repeated *** believe that ultrasound,a cheap and harmless technique also used for HCC screening in cirrhotic patients,could have an expanding role in the diagnosis and follow-up of sarcopenia in these patients.

关键词： Sarcopenia Ultrasound Cirrhosis Hepatocellular carcinoma Computed tomography

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Early diagnosis and management of neonatal sepsis:a perspective

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World Journal of Pediatrics 2024年第4期20卷 303-306页

作者： Li‑Zhong Du Neonatal Intensive Care unit Children’s Hospital Zhejiang University School of MedicineNational Clinical Research Center for Child Health3333 Binsheng RoadHangzhou 310052China

Neonatal sepsis is an illness caused by bloodstream bacteria or fungal infections that affect newborn infants under 28 days of *** stands as a significant contributor to morbidity and mortality in neonatal intensive care units(NICUs).With the improved survival rates of very low-birth-weight or extremely premature infants,a growing number of these vulnerable infants are receiving intensive care and undergoing invasive procedures,making nosocomial infections a persistent challenge in *** mortality rate associated with neonatal sepsis varies depending on factors such as birth weight,gestational age,and other *** can also lead to a range of long-term health consequences,including neurodevelopmental disabilities like cerebral palsy,visual or hearing impairments,and cognitive ***,neonatal sepsis is linked to various adverse outcomes,including respiratory complications,bronchopulmonary dysplasia,nutritional and growth issues,and immunological dysfunction[1].Due to its atypical clinical presentation and the low rate of specific diagnostic indicators,such as a positive blood culture,accurately diagnosing neonatal sepsis is ***,the appropriateness of antibiotic treatment is often a matter of controversy.

关键词： neonatal mortality diagnosis

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clinical prediction of insufficient vaults after implantable collamer lens implantation

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International Journal of Ophthalmology(English edition) 2024年第7期17卷 1300-1306页

作者： Jun Zhu Dan Cheng Xue-Ying Zhu Fen-Fen Li Ye Yang Yu-Feng Ye National clinical Research Center for Ocular Diseases Eye HospitalWenzhou Medical UniversityWenzhou 325027Zhejiang ProvinceChina

AIM:To determine the factors related to preoperative ocular characters that are predictive of insufficient vault(<250μm)after implantable collamer lens(ICL V4c;STAAR Surgical)***:The participants underwent ICL surger... 详细信息

AIM:To determine the factors related to preoperative ocular characters that are predictive of insufficient vault(clinical outcomes were compared between the two *** relationship between the 3-month vault values and preoperative ocular parameters were evaluated by Generalized estimating ***:Sixteen(23 eyes)and 36 patients(63 eyes)were in the low and normal vault groups,*** implantation procedures were uneventful with no cataract formation in the early postoperative *** sulcusto-sulcus lens rise(STSL)and iris ciliary angle(ICA)were correlated with vault at 3mo after *** 0.1 mm increase in STSL was associated with 38.9μm decrease in the postoperative 3-month vault.A rise of 1 degree in ICA is associated with a reduction of 4μm in ***:Eyes with a narrow ciliary sulcus are associated with a higher rate of low vault after ICL implantation,suggesting a need for adjustments to the ICL size in these *** the characteristics of the ciliary sulcus contributes valuable information to predict low vault after surgery.

关键词： insufficient vault implantable collamer lens ciliary body posterior chamber

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Anti-EGFR antibody monotherapy for colorectal cancer with severe hyperbilirubinemia: A case report

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World Journal of Gastrointestinal Oncology 2024年第2期16卷 557-562页

作者： Toshiaki Tsurui Yuya Hirasawa Yutaro Kubota Kiyoshi Yoshimura Takuya Tsunoda Department of Medical Oncology Showa UniversityTokyo 1428555Japan Department of clinical Immuno Oncology Clinical Research Institute of Clinical Pharmacology and TherapeuticsShowa UniversityTokyo 1578577Japan

BACKGROUND Hyperbilirubinemia with hepatic metastases is a common complication and a poor prognostic factor for colorectal cancer(CRC).Effective drainage is often im-possible before initiating systemic chemotherapy,owing to the liver’s diffuse metastatic ***,an appropriate chemotherapeutic approach for the treatment of hyperbilirubinemia is currently *** SUMMARY The patient,a man in his 50s,presented with progressive fatigue and severe *** tomography revealed multiple hepatic masses with thick-ened walls in the sigmoid colon,which was pathologically confirmed as a well-differentiated *** RAS or BRAF mutations were *** Eastern Cooperative Oncology Group(ECOG)performance status(PS)score was *** drainage was impossible due to the absence of a dilated bile duct,and panitumumab monotherapy was promptly ***,the bilirubin level decreased and then normalized,and the patient’s PS improved to zero ECOG score after four cycles of therapy without significant adverse *** Anti-EGFR antibody monotherapy is a safe and effective treatment for RAS wild-type CRC and hepatic metastases with severe hyperbilirubinemia.

关键词： Colorectal neoplasms Panitumumab Chemotherapy Hyperbilirubinemia Jaundice Case report

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RNA modifications in cellular metabolism:implications for metabolism-targeted therapy and immunotherapy

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1565-1594页

作者： Wei-Wei Liu Si-Qing Zheng Tian Li Yun-Fei Fei Chen Wang Shuang Zhang Fei Wang Guan-Min Jiang Hao Wang Department of Laboratory Medicine The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiChina School of clinical Medicine Shandong UniversityJinanChina Core unit of National clinical Research Center for Laboratory Medicine HefeiChina Neurosurgical Department The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiChina Department of clinical Laboratory The Fifth Affiliated HospitalSun Yat-sen UniversityZhuhaiChina

Cellular metabolism is an intricate network satisfying bioenergetic and biosynthesis requirements of *** studies have been constantly making inroads in our understanding of pathophysiology,and inspiring development of *** a crucial component of epigenetics at post-transcription level,RNA modification significantly determines RNA fates,further affecting various biological processes and cellular *** be noted,immunometabolism defines the metabolic alterations occur on immune cells in different stages and immunological *** this review,we characterize the distribution features,modifying mechanisms and biological functions of 8 RNA modifications,including N6-methyladenosine(m6A),N6,2'-O-dimethyladenosine(m6Am),N1-methyladenosine(m1A),5-methylcytosine(m5C),N4-acetylcytosine(ac4C),N7-methylguanosine(m7G),Pseudouridine(V),adenosine-to-inosine(A-to-l)editing,which are relatively the most studied *** regulatory roles of these RNA modification on metabolism in diverse health and disease contexts are comprehensively described,categorized as glucose,lipid,amino acid,and mitochondrial *** we highlight the regulation of RNA modifications on immunometabolism,further influencing immune *** all,we provide a thorough discussion about clinical implications of RNA modification in metabolism-targeted therapy and immunotherapy,progression of RNA modification-targeted agents,and its potential in RNAtargeted ***,we give legitimate perspectives for future researches in this field from methodological requirements,mechanistic insights,to therapeutic applications.

关键词： metabolism targeted alterations

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