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Hepatorenal syndrome:Update on diagnosis and therapy

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World Journal of Hepatology 2017年第6期9卷 293-299页

作者： juan g acevedo Matthew E Cramp South West Liver Unit Plymouth Hospitals Trust Hepatology Research group Plymouth University Peninsula Schools of Medicine and Dentistry

Hepatorenal syndrome(HRS) is a manifestation of extreme circulatory dysfunction and entails high morbidity and mortality.A new definition has been recently recommended by the International Club of Ascites,according to which HRS diagnosis relies in serum creatinine changes instead that on a fixed high ***,new data on urinary biomarkers has been recently *** this sense,the use of urinary neutrophil gelatinase-associated lipocalin seems useful to identify patients with acute tubular necrosis and should be employed in the diagnostic *** with terlipressin and albumin is the current standard of *** data show that terlipressin in intravenous continuous infusion is better tolerated than intravenous boluses and has the same *** is effective in reversing HRS in only 40%-50% of *** bilirubin and creatinine levels along with the increase in blood pressure and the presence of systemic inflammatory response syndrome have been identified as predictors of ***,there is a need for further research in novel *** treatments have been assessed such as noradrenaline,dopamine,transjugular intrahepatic portosystemic shunt,renal and liver replacement therapy,*** all of them,liver transplant is the only curative option and should be considered in all *** can be prevented with volume expansion with albumin during spontaneous bacterial peritonitis and after post large volume paracentesis,and with antibiotic prophylaxis in patients with advanced cirrhosis and low proteins in the ascitic *** manuscript reviews the recent advances in the diagnosis and management of this life-threatening condition.

关键词： Hepatorenal syndrome Acute-on-chronic liver failure Liver cirrhosis Terlipressin Acute kidney injury

Sensitivity of diagnosis of spontaneous bacterial peritonitis is higher with the automated cell count method

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World Journal of Hepatology 2024年第11期16卷 1265-1281页

作者： juan g acevedo-Haro Waddah Mohamed Prebashan Moodley Oliver Bendall Kris Bennett Nigel Keelty Sally Chan Sam Waddy Joanne Hosking Wayne Thomas Robert Tilley South West Liver Unit University Hospitals Plymouth NHS TrustPlymouth PL68DHUnited Kingdom Medical School University of PlymouthPlymouth PL68DHUnited Kingdom Intensive Care Unit University Hospitals Plymouth NHS TrustPlymouth PL68DHUnited Kingdom Medical Statistics group Peninsula Clinical Trials UnitUniversity of PlymouthPlymouth PL68DHUnited Kingdom Haematology Service University Hospitals Plymouth NHS TrustPlymouth PL68DHUnited Kingdom Microbiology Service University Hospitals Plymouth NHS TrustPlymouth PL68DHUnited Kingdom

BACKgROUND Spontaneous bacterial peritonitis(SBP)is one of the most important complications of patients with liver cirrhosis entailing high morbidity and *** an accurate early diagnosis of this infection is key in the outcome of these *** current definition of SBP is based on studies performed more than 40 years ago using a manual technique to count the number of polymorphs in ascitic fluid(AF).There is a lack of data comparing the traditional cell count method with a current automated cell ***,current international guidelines do not mention the type of cell count method to be employed and around half of the centers still rely on the traditional manual *** To compare the accuracy of polymorph count on AF to diagnose SBP between the traditional manual cell count method and a modern automated cell counter against SBP cases fulfilling gold standard criteria:Positive AF culture and signs/symptoms of *** Retrospective analysis including two cohorts:Cross-sectional(cohort 1)and case-control(cohort 2),of patients with decompensated cirrhosis and *** cell count methods were conducted *** SBP cases had a pathogenic bacteria isolated on AF and signs/symptoms of *** A total of 137 cases with 5 positive-SBP,and 85 cases with 33 positive-SBP were included in cohort 1 and 2,***-SBP cases had worse liver function in both *** automated method showed higher sensitivity than the manual cell count:80%vs 52%,P=0.02,in cohort *** methods showed very good specificity(>95%).The best cutoff using the automated cell counter was polymorph≥0.2 cells×10^(9)/L(equivalent to 200 cells/mm^(3))in AF as it has the higher sensitivity keeping a good *** The automated cell count method should be preferred over the manual method to diagnose SBP because of its higher *** definition,using the automated method,as polymorph cell count≥0.2 cells×1

关键词： Spontaneous bacterial peritonitis Diagnosis Cirrhosis Bacterial infection Automated cell count method Manual cell count method Ascitic fluid

Sequence-activated chemiluminescence probes: programmable illumination for high-contrast in vivo sensing and imaging

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Science China Chemistry 2025年第1期68卷 26-34页

作者： Yutao Zhang juan Li Wei-Hong Zhu Zhiqian guo Shanghai Key Laboratory of Functional Materials Chemistry Joint International Research Laboratory of Precision Chemistry and Molecular Engineering Institute of Fine Chemicals School of Chemistry and Molecular Engineering East China University of Science and Technology State Key Laboratory of Bioreactor Engineering Shanghai Frontier Science Research Base of Optogenetic Techniques for Cell MetabolismEast China University of Science & Technology

Sequence-activated chemiluminescence(CL) technique offers a unique approach to detecting specific biomolecules or cellular events with high sensitivity and spatial resolution. The fundamental principle behind sequence-activated CL probes involves tailoring highly-controllable CL signals in response to specific sequences or events of interest, thus enabling high-contrast signals under complex physiological conditions. This sequential activation could be triggered by enzymes, reactive oxygen species(ROS), biothiols or changes in the microenvironment. These unique sequence-activated CL probes bestow several advantages, including minimal background, deep-tissue penetration, and the ability of non-invasive or minimally invasive detection. The sequence-activated CL techniques represent a significant advancement in molecular imaging and diagnostics. In this mini-review, we focus on the latest developments in sequential CL probes, addressing the technical challenges and discussing the future trajectory by harnessing CL signaling and molecular recognition.

关键词： chemiluminescnece sequence-activation in-vivo bioimaging cyclic peroxide

Stiffness-tunable biomaterials provide a good extracellular matrix environment for axon growth and regeneration

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Neural Regeneration Research 2025年第5期20卷 1364-1376页

作者： Ronglin Han Lanxin Luo Caiyan Wei Yaru Qiao Jiming Xie Xianchao Pan juan Xing Department of Pathophysiology School of Basic Medical SciencesSouthwest Medical UniversityLuzhouSichuan ProvinceChina Department of Medicinal Chemistry School of PharmacySouthwest Medical UniversityLuzhouSichuan ProvinceChina

Neuronal growth, extension, branching, and formation of neural networks are markedly influenced by the extracellular matrix—a complex network composed of proteins and carbohydrates secreted by cells. In addition to providing physical support for cells, the extracellular matrix also conveys critical mechanical stiffness cues. During the development of the nervous system, extracellular matrix stiffness plays a central role in guiding neuronal growth, particularly in the context of axonal extension, which is crucial for the formation of neural networks. In neural tissue engineering, manipulation of biomaterial stiffness is a promising strategy to provide a permissive environment for the repair and regeneration of injured nervous tissue. Recent research has fine-tuned synthetic biomaterials to fabricate scaffolds that closely replicate the stiffness profiles observed in the nervous system. In this review, we highlight the molecular mechanisms by which extracellular matrix stiffness regulates axonal growth and regeneration. We highlight the progress made in the development of stiffness-tunable biomaterials to emulate in vivo extracellular matrix environments, with an emphasis on their application in neural repair and regeneration, along with a discussion of the current limitations and future prospects. The exploration and optimization of the stiffness-tunable biomaterials has the potential to markedly advance the development of neural tissue engineering.

关键词： alginate axon growth biomaterials extracellular matrix neural repair neurons neuroregeneration polyacrylamide polydimethylsiloxane stiffness

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Anti-amyloid antibodies in Alzheimer’s disease: what did clinical trials teach us?

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Neural Regeneration Research 2025年第4期20卷 1092-1093页

作者： Danko Jeremic Lydia Jiménez-Díaz juan D.Navarro-López NeuroPhysiology&Behavior Lab University of Castilla-La ManchaBiomedical Research Center(CRIB)School of Medicine of Ciudad RealCiudad RealSpain

Although many causes of Alzheimer’s disease(AD)may exist,both the original amyloid cascade and tau hypotheses posit that abnormal misfolding and accumulation of amyloid-β(Aβ)and tau protein is the central event causing the ***,that conclusion could be only partly true,and there is conflicting evidence about the role of both proteins in AD,being able to precede and influence one *** researchers argue that these proteins are mere executors rather than primary causes of ***,there have been continuing refinements of both hypotheses,with alternative explanations proposed.Aβand tau proteins may be independently involved in specific neurotoxic pathways;yet there may be other crucial processes going on in early ***,accumulating evidence suggests that Aβand tau act synergistically,rather than additively in disease onset(Jeremic et al.,2021,2023a).

关键词： amyloid Alzheimer additive

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Milking the Market

China Today 2025年第1期74卷 39-41页

作者： HOU juan China Economic Weekly

With climate change becoming direr and the WTO losing its teeth at 30,experts renew call for green collaboration among the world’s three largest *** competition intensifies in the global dairy product market,many foreign dairy companies are focusing on China."China is the best market to debut breakthrough products,"said Bruno Chevot,food and beverage multinational Danone China’s president for North Asia and Oceania.

关键词： companies Market China.

A Mn-porphyrinic metal–organic framework immobilizing glucose oxidase for combined photodynamic/chemodynamic/starvation therapy

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Tungsten 2025年第1期7卷 183-194页

作者： Xin-Ran Sun Hao-Ming Yuan guo-Da Zhang Chao Wang Shu-juan Sun Peng-Fei Shi Shandong Provincial Key Laboratory of Detection Technology for Tumor Markers School of Chemistry and Chemical Engineering Linyi University

The combination of photodynamic therapy（PDT） and chemodynamic therapy（CDT） in tumor treatment has attracted considerable ***,tumor hypoxia and glutathione（gSH） overproduction in the tumor tissue restricted the progress of their ***,a Mn-porphyrinic metal-organic framework（Mn-TCPP） was constructed by the one-pot method and further used for immobilizing glucose oxidase（gOx） to obtain gOx@*** would rapidly exhaust endogenous glucose into hydrogen peroxide（H2O2） and gluconic acid,thus shutting off the energy supply of tumor cells for starvation ***-TCPP catalyzed H2O2to produce oxygen,regulating the hypoxic tumor microenvironment and in turn improving1O2generation under laser ***,Mn-TCPP can reduce reactive oxygen species consumption owing to the redox reaction between Mn3+and gSH,thus greatly enhancing ***,benefiting from gOx-mediated starvation therapy,Mn2+produced by Mn3+reduction can react with sufficient intracellular H2O2to generate ·OH with high cytotoxicity through a Fenton-like *** treatment by gOx@Mn-TCPP under laser irradiation in vitro,the cell viability of 4T1 and A549 tumor cells reached to 20%,reflecting gOx@Mn-TCPP could give full play to the advantages of PDT/CDT/starvation *** results in vivo demonstrated that gOx@Mn-TCPP mediated synergistic cascade therapy could significantly inhibit tumor growth and improve the therapeutic effect.

关键词： Chemodynamic therapy Immobilizing enzyme Metal–organic frameworks Photodynamic therapy Starvation therapy

Salsolinol as an RNA m~6A methylation inducer mediates dopaminergic neuronal death by regulating YAP1 and autophagy

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Neural Regeneration Research 2025年第3期20卷 887-899页

作者： Jianan Wang Yuanyuan Ran Zihan Li Tianyuan Zhao Fangfang Zhang juan Wang Zongjian Liu Xuechai Chen Beijing International Science and Technology Cooperation Base for Antiviral Drugs College of Chemistry and LifeBeijing University of TechnologyBeijingChina Department of Rehabilitation Beijing Rehabilitation HospitalCapital Medical UniversityBeijingChina

Salsolinol(1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline,Sal)is a catechol isoquinoline that causes neurotoxicity and shares structural similarity with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine,an environmental toxin that causes Parkinson's ***,the mechanism by which Sal mediates dopaminergic neuronal death remains *** this study,we found that Sal significantly enhanced the global level of N~6-methyladenosine(m~6A)RNA methylation in PC12 cells,mainly by inducing the downregulation of the expression of m~6A demethylases fat mass and obesity-associated protein(FTO)and alk B homolog 5(ALKBH5).RNA sequencing analysis showed that Sal downregulated the Hippo signaling *** m~6A reader YTH domain-containing family protein 2(YTHDF2)promoted the degradation of m~6A-containing Yes-associated protein 1(YAP1)mRNA,which is a downstream key effector in the Hippo signaling ***,downregulation of YAP1 promoted autophagy,indicating that the mutual regulation between YAP1 and autophagy can lead to *** findings reveal the role of Sal on m~6A RNA methylation and suggest that Sal may act as an RNA methylation inducer mediating dopaminergic neuronal death through YAP1 and *** results provide greater insights into the neurotoxic effects of catechol isoquinolines compared with other studies and may be a reference for assessing the involvement of RNA methylation in the pathogenesis of Parkinson's disease.

关键词： ALKBH5 autophagy FTO Hippo pathway m~6A Parkinson's disease RNA methylation salsolinol YAP1 YTHDF2

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New determinants of prognosis in bacterial infections in cirrhosis

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World Journal of gastroenterology 2014年第23期20卷 7252-7259页

作者： juan acevedo Javier Fernández Department of gastroenterology and Hepatology Hospital of Calella08370 BarcelonaCatalunyaSpain Liver Unit Hospital ClínicUniversity of Barcelona08150 BarcelonaCatalunyaSpain Institut d’Investigacions Biomèdiques August-Pi-Sunyer (IDIBAPS) 08036 BarcelonaSpain Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHED) 08150 BarcelonaSpain

Despite major advances in the knowledge and management of liver diseases achieved in recent decades,decompensation of cirrhosis still carries a high burden of morbidity and *** infections are one of the main causes of *** is very important for clinical management to be aware of the population with the highest risk of poor *** review deals with the new determinants of prognosis in patients with cirrhosis and bacterial infections reported *** of multiresistant bacteria has led to an increasing failure rate of the standard empirical antibiotic therapy recommended by international ***,it has been recently reported that endothelial dysfunction is associated with the degree of liver dysfunction and,in infected patients,with the degree of *** has also been reported that relative adrenal insufficiency is frequent in the non-critically ill cirrhotic population and it is associated with a higher risk of developing infection,severe sepsis,hepatorenal syndrome and *** advise a change in the standard empirical antibiotic therapy in patients with high risk for multiresistant infections and also to take into account endothelial and adrenal dysfunction in prognostic models in hospitalized patients with decompensated cirrhosis.

关键词： Bacterial infections Liver cirrhosis Drug resistance Bacterial Endothelial dysfunction Relative adrenal insufficiency