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Red cell distribution width/platelet ratio estimates the 3-year risk of decompensation in Metabolic Dysfunction-Associated Steatotic Liver Disease-induced cirrhosis

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World Journal of Gastroenterology 2024年第7期30卷 685-704页

作者： Marcello Dallio Mario Romeo Paolo Vaia Salvatore Auletta Simone Mammone Marina Cipullo Luigi Sapio Angela Ragone Marco Niosi Silvio Naviglio Alessandro Federico Department of precision medicine Hepatogastroenterology DivisionUniversity of Campania Luigi VanvitelliNaples 80138Italy Department of precision medicine Clinical Biochemistry DivisionUniversity of Campania Luigi VanvitelliNaples 80138Italy

BACKGROUND For compensated advanced chronic liver disease(cACLD)patients,the first decompensation represents a dramatically worsening prognostic event.Based on the first decompensation event(DE),the transition to decompensated advanced chronic liver disease(dACLD)can occur through two modalities referred to as acute decompensation(AD)and non-AD(NAD),respectively.Clinically Significant Portal Hypertension(CSPH)is considered the strongest predictor of decompensation in these patients.However,due to its invasiveness and costs,CSPH is almost never evaluated in clinical practice.Therefore,recognizing noninvasively predicting tools still have more appeal across healthcare systems.The red cell distribution width to platelet ratio(RPR)has been reported to be an indicator of hepatic fibrosis in Metabolic Dysfunction-Associated Steatotic Liver Disease(MASLD).However,its predictive role for the decompensation has never been explored.AIM In this observational study,we investigated the clinical usage of RPR in predicting DEs in MASLD-related cACLD patients.METHODS Fourty controls and 150 MASLD-cACLD patients were consecutively enrolled and followed up(FUP)semiannually for 3 years.At baseline,biochemical,clinical,and Liver Stiffness Measurement(LSM),Child-Pugh(CP),Model for End-Stage Liver Disease(MELD),aspartate aminotransferase/platelet count ratio index(APRI),Fibrosis-4(FIB-4),Albumin-Bilirubin(ALBI),ALBI-FIB-4,and RPR were collected.During FUP,DEs(timing and modaities)were recorded.CSPH was assessed at the baseline and on DE occurrence according to the available Clinical Practice Guidelines.RESULTS Of 150 MASLD-related cACLD patients,43(28.6%)progressed to dACLD at a median time of 28.9 months(29 NAD and 14 AD).Baseline RPR values were significantly higher in cACLD in comparison to controls,as well as MELD,CP,APRI,FIB-4,ALBI,ALBI-FIB-4,and LSM in dACLD-progressing compared to cACLD individuals[all P0.472 and>0.894 as the best

关键词： Liver cirrhosis Red blood cell distribution width Red blood cell distribution width to platelet ratio Translational medicine Prognostic biomarker

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Angiotensin-converting enzyme 2 and AMPK/mTOR pathway in the treatment of liver fibrosis:Should we consider further implications?

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World Journal of Gastroenterology 2024年第18期30卷 2391-2396页

作者： Michele Barone Section of Gastroenterology Department of Precision and Regenerative Medicine-Jonian Area-University of BariBari 70124Italy

This editorial contains comments on the article by Zhao et al in print in the World Journal of Gastroenterology.The mechanisms responsible for hepatic fibrosis are also involved in cancerogenesis.Here,we recapitulated the complexity of the renin-angiotensin system,discussed the role of hepatic stellate cell(HSC)autophagy in liver fibrogenesis,and analyzed the possible implications in the development of hepatocarcinoma(HCC).Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers definitively contribute to reducing hepatic fibrogenesis,whereas their involvement in HCC is more evident in experimental conditions than in human studies.Angiotensin-converting enzyme 2(ACE2),and its product Angiotensin(Ang)1-7,not only regulate HSC autophagy and liver fibrosis,but they also represent potential targets for unexplored applications in the field of HCC.Finally,ACE2 overexpression inhibits HSC autophagy through the AMP-activated protein kinase(AMPK)/mammalian target of rapamycin(mTOR)pathway.In this case,Ang 1-7 acts binding to the MasR,and its agonists could modulate this pathway.However,since AMPK utilizes different targets to suppress the mTOR downstream complex mTOR complex 1 effectively,we still need to unravel the entire pathway to identify other potential targets for the therapy of fibrosis and liver cancer.

关键词： Renin-angiotensin system Liver fibrosis Hepatic stellate cells Autophagy Hepatocellular carcinoma

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Hepatitis B virus genotypes in precision medicine of hepatitis Brelated hepatocellular carcinoma:Where we are now

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1097-1103页

作者： Caecilia H C Sukowati Sri Jayanti Turyadi Turyadi David H Muljono Claudio Tiribelli Eijkman Research Center for Molecular Biology Research Organization for HealthNational Research and Innovation Agency of IndonesiaJakarta 10340Indonesia Liver Cancer unit Fondazione Italiana Fegato ONLUSTrieste 34149Italy Faculty of medicine Hasanuddin UniversityMakassar 90245South SulawesiIndonesia Faculty of medicine and Health University of SydneySydney 2050Australia

Hepatitis B virus(HBV)infection is a major player in chronic hepatitis B that may lead to the development of hepatocellular carcinoma(HCC).HBV genetics are diverse where it is classified into at least 9 genotypes(A to I)and 1 putative genotype(J),each with specific geographical distribution and possible different clinical outcomes in the patient.This diversity may be associated with the precision medicine for HBV-related HCC and the success of therapeutical approaches against HCC,related to different pathogenicity of the virus and host response.This Editorial discusses recent updates on whether the classification of HBV genetic diversity is still valid in terms of viral oncogenicity to the HCC and its precision medicine,in addition to the recent advances in cellular and molecular biology technologies.

关键词： Hepatitis B virus Hepatocellular carcinoma Genotypes Pathogenesis precision medicine

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May ChatGPT be a tool producing medical information for common inflammatory bowel disease patients’questions?An evidencecontrolled analysis

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World Journal of Gastroenterology 2024年第1期30卷 17-33页

作者： Antonietta Gerarda Gravina Raffaele Pellegrino Marina Cipullo Giovanna Palladino Giuseppe Imperio Andrea Ventura Salvatore Auletta Paola Ciamarra Alessandro Federico Division of Hepatogastroenterology Department of Precision MedicineUniversity of Campania Luigi VanvitelliNaples 80138Italy

Artificial intelligence is increasingly entering everyday healthcare.Large language model(LLM)systems such as Chat Generative Pre-trained Transformer(ChatGPT)have become potentially accessible to everyone,including patients with inflammatory bowel diseases(IBD).However,significant ethical issues and pitfalls exist in innovative LLM tools.The hype generated by such systems may lead to unweighted patient trust in these systems.Therefore,it is necessary to understand whether LLMs(trendy ones,such as ChatGPT)can produce plausible medical information(MI)for patients.This review examined ChatGPT’s potential to provide MI regarding questions commonly addressed by patients with IBD to their gastroenterologists.From the review of the outputs provided by ChatGPT,this tool showed some attractive potential while having significant limitations in updating and detailing information and providing inaccurate information in some cases.Further studies and refinement of the ChatGPT,possibly aligning the outputs with the leading medical evidence provided by reliable databases,are needed.

关键词： Crohn’s disease Ulcerative colitis Inflammatory bowel disease Chat Generative Pre-trained Transformer Large language model Artificial intelligence

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HIF-1αpromotes virus replication and cytokine storm in H1N1 virus-induced severe pneumonia through cellular metabolic reprogramming

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Virologica Sinica 2024年第1期39卷 81-96页

作者： Xiaoxiao Meng Yong Zhu Wenyu Yang Jiaxiang Zhang Wei Jin Rui Tian Zhengfeng Yang Ruilan Wang Department of Critical Care medicine Shanghai General HospitalShanghai Jiaotong UniversitySchool of MedicineShanghai201620China precision Research Center for Refractory Diseases Shanghai General HospitalShanghai Jiaotong UniversitySchool of MedicineShanghai201620China

The mortality of patients with severe pneumonia caused by H1N1 infection is closely related to viral replication and cytokine storm.However,the specific mechanisms triggering virus replication and cytokine storm are still not fully elucidated.Here,we identified hypoxia inducible factor-1α(HIF-1α)as one of the major host molecules that facilitates H1N1 virus replication followed by cytokine storm in alveolar epithelial cells.Specifically,HIF-1αprotein expression is upregulated after H1N1 infection.Deficiency of HIF-1αattenuates pulmonary injury,viral replication and cytokine storm in vivo.In addition,viral replication and cytokine storm were inhibited after HIF-1αknockdown in vitro.Mechanistically,the invasion of H1N1 virus into alveolar epithelial cells leads to a shift in glucose metabolism to glycolysis,with rapid production of ATP and lactate.Inhibition of glycolysis significantly suppresses viral replication and inflammatory responses.Further analysis revealed that H1N1-induced HIF-1αcan promote the expression of hexokinase 2(HK2),the key enzyme of glycolysis,and then not only provide energy for the rapid replication of H1N1 virus but also produce lactate,which reduces the accumulation of the MAVS/RIG-I complex and inhibits IFN-α/βproduction.In conclusion,this study demonstrated that the upregulation of HIF-1αby H1N1 infection augments viral replication and cytokine storm by cellular metabolic reprogramming toward glycolysis mainly through upregulation of HK2,providing a theoretical basis for finding potential targets for the treatment of severe pneumonia caused by H1N1 infection.

关键词： H1N1 Severe pneumonia Virus replication Hypoxia inducible factor-1α Glycolysis

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One-pot and One-step Cu(0)-mediated Reversible-Deactivation Radical Polymerization of N-Isopropylacrylamide(NIPAM) in Water

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Chinese Journal of Polymer Science 2024年第1期42卷 1-6,I0004页

作者： Zi-Shan Li Jing Lyu Bei Qiu Ying-Hao Li Ruth Foley Ri-Jian Song Melissa Johnson Qiang Geng Wen-Xin Wang Institute of precision medicine(AUST-IPM) Anhui University of Science and TechnologyHuainan 232001China Charles Institute of Dermatology School of MedicineUniversity College DublinDublin D04 V1W8Ireland

Copper(0)-mediated reversible-deactivation radical polymerization(Cu(0)-mediated RDRP) of the water-soluble monomer Nisopropylacrylamide(NIPAM) has been challenging with the problems of high dispersity, poor control over the molecular weights(MWs) or complex or multi reaction steps, etc. In this work, we report the well-controlled polymerization of NIPAM in water via a facile one-pot and one-step Cu(0)-mediated RDRP. The results of this approach show that the key for kicking off the Cu(0)-mediated NIPAM RDRPs is to ensure sufficient Cu~I at the very beginning, and the key to achieve a well-controlled chain growth is to provide adequate deactivation strength during the polymerization process. For NIPAM, which has a high propagation rate constant, the deactivation control can be effectively enhanced by extra adding deactivator(i.e., Cu~II) to the system. Moreover, a low reaction temperature(4 ℃) is necessary in the controlled synthesis of higher MW poly(Nisopropylacrylamide)(PNIPAM) to avoid the compromise in control caused by the phase transition from its lower critical solution temperature(LCST). Through this new kinetically controlled strategy, PNIPAMs with well-defined structure, narrow molecular weight distributions(MWDs) and varied MWs were successfully achieved.

关键词： Cu(0)-mediated RDRP N-isopropylacrylamide Propagation Deactivation Reaction parameters

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The Application of Permanent Magnet Synchronous Motor with Small Electrical Time Constant in Fiber Positioner

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Research in Astronomy and Astrophysics 2024年第1期24卷 212-222页

作者： Shaoxiong Guo Yan Yang Yanbin Yin Yihu Tang Yang Tian Chao Zhai Department of precision Machinery and precision Instrumentation University of Science and Technology of ChinaHefei 230026China School of Biomedical Engineering Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230026China Experiment Center of Engineering and Material Science University of Science and Technology of ChinaHefei 230026China

With the development of cutting-edge multi-object spectrographs,fiber positioners located in the focal plane are being scaled down in size,and miniature hollow-cup Permanent Magnet motors are now being considered as a suitable replacement for Faulhaber Precistep stepper motors.However,the small electrical time constant of such coreless motors poses a challenge,as the problem of severe commutation torque ripple in a fiber positioner running a position loop has been tricky.To overcome this challenge,it is advised to increase the Pulse Width Modulation(PWM)frequency as much as possible to mitigate the effects of the current fluctuation.This must be done while ensuring adequate resolution of the PWM generator.By employing a voltage open-loop field-oriented control based on a modulation frequency of 1 MHz,the drive current only costs 25 m A under a 3.3 V power supply.The sine degree of phase current is immaculate,and the repeat positioning accuracy can reach 2μm.Moreover,it is possible to further shrink the bill of devices and the layout area of the Printed Circuit Board,especially in sizesensitive applications.This device has been developed under the new generation of The Large Sky Area MultiObject Fiber Spectroscopic Telescope.

关键词： instrumentation:adaptive optics instrumentation:spectrographs proper motions reference systems

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Improving the value of molecular testing:current status and opportunities in colorectal cancer precision medicine

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Cancer Biology & medicine 2024年第1期21卷 21-28页

作者： Haiyun Li Linwei Guo Chenchen Wang Xin Hu Ye Xu Department of Colorectal Surgery Fudan University Shanghai Cancer CenterShanghai 200032China Department of Oncology Shanghai Medical CollegeFudan UniversityShanghai 200032China Department of Gastrointestinal Medical Oncology Fudan University Shanghai Cancer CenterShanghai 200032China precision Cancer Medical Center Affiliated with Fudan University Shanghai Cancer Center Shanghai 201315China

Colorectal cancer(CRC)is the second leading cause of cancer-related deaths worldwide1.Surgical radical resection with adjuvant chemotherapy remains the primary treatment choice for CRC,but the 5-year postoperative survival rate is only approximately 60%,and approximately one-third of patients with CRC experience recurrence within 2 years of surgery2.Fortunately,the transformation of high-throughput sequencing has accelerated the development of precision medicine.For example,KRAS mutations indicate resistance to anti-epidermal growth factor receptor(EGFR)-targeted therapies in CRC3.Furthermore,molecular-guided individualized therapy has brought new promise in major clinical areas and challenges,such as novel biomarkers predicting sensitivity and resistance to immunotherapy for microsatellite stable(MSS)CRC.

关键词： cancer chemotherapy colorectal

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Post-acute ischemic stroke hyperglycemia aggravates destruction of the blood-brain barrier

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Neural Regeneration Research 2024年第6期19卷 1344-1350页

作者： Tianqi Xu Jianhong Yang Yao Xu Xiaofeng Wang Xiang Gao Jie Sun Chenhui Zhou Yi Huang Department of Neurology The First Affiliated Hospital of Ningbo University Department of General Surgery The First Affiliated Hospital of Ningbo University Department of Neurosurgery The First Affiliated Hospital of Ningbo University Key Laboratory of precision medicine for Atherosclerotic Diseases of Zhejiang Province

Post-acute ischemic stroke hyperglycemia increases the risk of hemorrhagic transformation, which is associated with blood-brain barrier disruption. Brain microvascular endothelial cells are a major component of the blood-brain barrier. Intercellular mitochondrial transfer has emerged as a novel paradigm for repairing cells with mitochondrial dysfunction. In this study, we first investigated whether mitochondrial transfer exists between brain microvascular endothelial cells, and then investigated the effects of post-acute ischemic stroke hyperglycemia on mitochondrial transfer between brain microvascular endothelial cells. We found that healthy brain microvascular endothelial cells can transfer intact mitochondria to oxygen glucose deprivation-injured brain microvascular endothelial cells. However, post-oxygen glucose deprivation hyperglycemia hindered mitochondrial transfer and exacerbated mitochondrial dysfunction. We established an in vitro brain microvascular endothelial cell model of the blood-brain barrier. We found that post-acute ischemic stroke hyperglycemia reduced the overall energy metabolism levels of brain microvascular endothelial cells and increased permeability of the blood-brain barrier. In a clinical study, we retrospectively analyzed the relationship between post-acute ischemic stroke hyperglycemia and the severity of hemorrhagic transformation. We found that post-acute ischemic stroke hyperglycemia serves as an independent predictor of severe hemorrhagic transformation. These findings suggest that post-acute ischemic stroke hyperglycemia can aggravate disruption of the blood-brain barrier by inhibiting mitochondrial transfer.

关键词： acute ischemic stroke blood-brain barrier brain microvascular endothelial cells mitochondrial transfer stress hyperglycemia

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Advances in microfluidic-based DNA methylation analysis

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Nanotechnology and precision Engineering 2024年第1期7卷 116-134页

作者： Jiwen Li Tiechuan Li Xuexin Duan State Key Laboratory of precision Measuring Technology and Instruments Tianjin UniversityTianjin 300072China

DNA methylation has been extensively investigated in recent years,not least because of its known relationship with various diseases.Progress in analytical methods can greatly increase the relevance of DNA methylation studies to both clinical medicine and scientiﬁc research.Microﬂu-idic chips are excellent carriers for molecular analysis,and their use can provide improvements from multiple aspects.On-chip molecular analysis has received extensive attention owing to its advantages of portability,high throughput,low cost,and high efﬁciency.In recent years,the use of novel microﬂuidic chips for DNA methylation analysis has been widely reported and has shown obvious superiority to conventional methods.In this review,weﬁrst focus on DNA methylation and its applications.Then,we discuss advanced microﬂuidic-based methods for DNA methylation analysis and describe the great progress that has been made in recent years.Finally,we summarize the advantages that microﬂuidic technology brings to DNA methylation analysis and describe several challenges and perspectives for on-chip DNA methylation analysis.This review should help researchers improve their understanding and make progress in developing microﬂuidic-based methods for DNA methylation analysis.

关键词： Microﬂuidic chip DNA methylation analysis Molecular analysis High throughput Low cost

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