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Twist1-induced miR-199a-3p promotes liver fibrosis by suppressing caveolin-2 and activating TGF-βpathway

Signal Transduction and Targeted Therapy 2020年第1期5卷 1732-1743页

作者： Xiaoxue Yang Liping Ma Rong Wei Tinghong Ye JianKang Zhou maoyao wen Ruoting Men Rami I.Aqeilan Yong Peng Li Yang Department of Gastroenterology&Hepatology West China HospitalSichuan UniversityChengdu 610041China State Key Laboratory of Biotherapy and Cancer Centre West China HospitalSichuan Universityand Collaborative Innovation Centre for BiotherapyChengdu 610041China School of Bioscience and Technology Chengdu medical collegeChengdu 610500China Department of Immunology&Cancer Research Hebrew University-Hadassah Medical SchoolJerusalemIsrael

The activation of hepatic stellate cells(HSCs)participates in liver fibrosis,and emerging evidences indicate that microRNAs(miRNAs)are abnormally expressed during HSC ***,the potential roles of miRNAs in liver fibrosis still remain ***,this study aimed to investigate the role of miR-199a-3p in liver fibrosis and its underlying *** found that miR-199a-3p expression was dramatically upregulated during HSC activation in vitro,and during liver fibrogenesis in CCl4-treated rats,and its liver expression was increased in the patients with *** the luciferase assay and RT-qPCR,we revealed that the expression of miR-199a-3p in HSCs was driven by the transcription factor Twist1 which could be further induced by TGF-β*** studies showed that inhibition of miR-199a-3p in both human LX2 cells and rat HSCs significantly decreased the expression of fibrotic markers,such as fibronectin and connective tissue growth factor(CTGF),whereas the forced expression of miR-199a-3p exhibited opposite effects,demonstrating the role of miR-199a-3p in promoting HSC ***,miR-199a-3p plays an important role in TGF-βsignalling pathway activation through targeting CAV2 that negatively regulates the expression of transforming growth factor-beta receptor type I(TGFβRI).Importantly,administration of antagomiR-199a-3p in the CCl4-treated mice significantly ameliorated hepatic *** conclusion,Twist1-induced miR-199a-3p mediates the activation of HSCs by suppressing CAV2 expression and subsequently increasing TGFβRI expression to promote TGF-β*** findings highlight the therapeutic potential of miR-199a-3p for hepatic fibrosis.

关键词： Twist1 miR hepatic

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Sequential therapy or standard triple therapy for Helicobacter pylori infection:a systematic review and meta-analysis

Sequential therapy or standard triple therapy for Helicobact...

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第十七届西南地区消化病学术会议暨2014贵州省消化病及消化内镜学术年会

作者： Li Feng maoyao wen YongJun Zhu RuoTing Men Li Yang Division of Digestive Diseases West China Hospital of Sichuan University Division of Digestive Diseases Affiliated Hospital of North Sichuan Medical Collage

BACKGROUND:The effectiveness of standard triple therapy(STT)for the eradication of Helicobacter pylori(HP)has decreased *** therapy(SQT)is a new regimen proposed to address this ***:To compare the efficacy of SQT versus STT for HP ***:We performed a systematic review of the literature and pooled-data *** eradication rates were based on an intention-to-treat(ITT)and per-protocol(PP)*** risk ratios(RR)of eradication rate were pooled,with a 95%***:A total of 33 trials met the inclusion *** ITT and PP eradication rates were 80.4%and 88.7%in SQT,and 74.9%and 78.6%in STT,*** RR for eradication of HP with SQT compared with STT was 1.14(95%CI:1.09-1.18)for ITT analysis and 1.14(95%CI:1.10-1.19)for PP *** was significant heterogeneity between trial results(I=72%,P<0.0001).Subgroup analyses showed that SQT was superior to both 7-day and 10-day STT,but was not significantly better than 14-day *** were no significant differences between groups in terms of the risk of adverse ***:SQT is more efficacious than STT(7-day and 10-day)in the eradication of HP,but the pooled rate seemed *** research is needed to develop more effective therapeutic approaches,regional monitoring of resistance rates should performed to help guide treatment.

关键词： Eradication Helicobacter pylori Meta-analysis Triple therapy Sequential therapy

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Circulating Nogo-B are correlated with liver cirrhosis

Circulating Nogo-B are correlated with liver cirrhosis

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第十七届西南地区消化病学术会议暨2014贵州省消化病及消化内镜学术年会

作者： maoyao wen Ruoting Men Yongjun Zhu Xuelian Dan wenchao Wu Xiaojing Liu Li Yang Division of Digestive Diseases West China HospitalSichuan University Laboratory of Cardiovascular Diseases Regenerative Medicine Research CenterWest China HospitalSichuan University

Aim:To evaluate the significance of plasma Nogo-B levels in patients with liver ***:Plasma Nogo-B levels were determined by enzyme linked immunosorbent assay(ELISA)in 301patients with liver cirrhosis and 130 healthy *** parameters were analyzed for the possible relationship with plasma ***:Plasma Nogo-B levels were significantly higher in liver cirrhotic patients(429.84±226.66 pg/mL)than in healthy controls(218.08±77.02 pg/mL,P0.05).Nogo-B levels were the highest in Child-Pugh class C patients among all the Child-Pugh class.(Child-Pugh class A:328.44±141.17 pg/mL,Child-Pugh class B:402.51±179.33 pg/mL,Child-Pugh class C:625.79±273.36 pg/mL,P<0.05).Plasma Nogo-B levels were positively correlated with INR(r=0.523,P=0.000)and negatively with albumin(r=-0.530,P=0.000).Plasma Nogo-B levels were significantly increased in patients with grade 3 ascites(533.25±236.58 pg/mL)than those with grade 1 ascites(351.53±198.88pg/mL)and without ascites(342.73±158.10 pg/mL)(P<0.05).Receiver operating characteristic analysis revealed that a plasma NogoB reading of 291.78 pg/mL provided a sensitivity of 61.8%and a specificity of89.6%).The area under the ROC curve of NogoB in discriminating patients with hepatic cirrhosis from healthy people was 0.815(95%confidence interval:0.771-0.858,P<0.,001).Conclusions:Plasma Nogo-B levels are increased in patients with hepatic cirrhosis while there is no significant difference among patients with different etiologies of ***,the concentrations of Nogo-B are correlated with some clinical parameters of hepatic cirrhosis.

关键词： Plasma Nogo-B hepatic cirrhosis the severity of liver diseases

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体检发现急性上消化道出血一例

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中华健康管理学杂志 2021年第2期15卷 186-187页

作者：文茂瑶胡梦瑶黄燕四川大学华西医院健康管理中心成都610041

急性上消化道出血是内科常见急症之一,如不及时诊治,有可能危及生命。因此,对上消化道出血患者应尽快明确出血部位及原因,以选择相应的治疗方案。本例在健康体检进行磁控胶囊胃镜检查时发现急性上消化道出血,通过迅速有效的处理,及时明... 详细信息

急性上消化道出血是内科常见急症之一,如不及时诊治,有可能危及生命。因此,对上消化道出血患者应尽快明确出血部位及原因,以选择相应的治疗方案。本例在健康体检进行磁控胶囊胃镜检查时发现急性上消化道出血,通过迅速有效的处理,及时明确了出血原因,避免耽误了患者病情。

关键词：胃肠道出血十二指肠溃疡健康体检

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不同评分系统对失代偿期肝硬化患者短期和中期死亡风险预测能力的比较

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临床肝胆病杂志 2017年第7期33卷 1284-1290页

作者：凡小丽文茂瑶沈怡杨丽四川大学华西医院消化内科成都610041

目的比较Child-Turcotte-Pugh(CTP)评分、MELD评分、MELD-Na评分、iMELD评分以及MESO指数对失代偿期肝硬化患者3、12个月死亡风险的预测价值。方法回顾性分析2014年1月1日-2014年12月31日于四川大学华西医院消化内科住院的269例失代偿... 详细信息

目的比较Child-Turcotte-Pugh(CTP)评分、MELD评分、MELD-Na评分、iMELD评分以及MESO指数对失代偿期肝硬化患者3、12个月死亡风险的预测价值。方法回顾性分析2014年1月1日-2014年12月31日于四川大学华西医院消化内科住院的269例失代偿期肝硬化患者的资料。计算患者入院48 h以内评估得到的上述评分分值,并对所有患者随访至1年以上。满足正态分布的计量资料组间比较若方差齐性采用t检验;不满足正态分布的计量资料组间比较采用Mann-Whitney U检验。计数资料组间比较采用χ~2检验;采用logistic回归分析法进行多因素分析、Hosmer-Lemeshow检验各模型拟合度、Kaplan-Meier生存分析法对生存率进行分析。结果 3个月内死亡患者25例,12个月内死亡患者38例;TBil、肌酐、尿素、Alb、WBC、PT、INR、血钠、入院时是否合并肝性脑病、腹水程度、入院时CTP评分、MELD评分、MELD-Na评分、iMELD评分、MESO评分、既往是否出现肝性脑病、出院后是否对因治疗等因素在12个月内死亡患者与存活患者间差异均有统计学意义(P值均<0.05);CTP评分、MELD评分、MELD-Na评分、iMELD评分以及MESO指数都是影响预后的独立危险因素(比值比分别为2.020、1.252、1.088、1.114、1.368,P值均<0.01)。对患者入院日起3个月内和12个月内死亡风险进行预测,CTP评分、MELD评分、MELD-Na评分、iMELD评分以及MESO指数中CTP评分的受试者工作特征曲线下面积(AUC)最高(3个月的AUC分别为0.823、0.789、0.775、0.770、0.796;12个月的AUC分别为0.834、0.798、0.777、0.801、0.804)。用各项评分的受试者工作特征曲线的判断值行12个月内生存分析,5种评分方法都能很好地区分患者12个月以内的累积生存率(P值均<0.05)。结论 CTP评分、MELD评分以及3个MELD相关评分都能很好地预测肝硬化患者短期和中期的死亡风险。对于中国人群,CTP评分对肝硬化患者死亡风险的预测能力可能相对较好。

关键词：肝硬化预后对比研究

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Targeting TrkB–PSD-95 coupling to mitigate neurological disorders

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Neural Regeneration Research 2025年第3期20卷 715-724页

作者： Xin Yang Yu-wen Alvin Huang John Marshall Department of Molecular Biology Cell Biology and BiochemistryBrown UniversityProvidenceRIUSA Department of Neurology Warren Alpert Medical School of Brown UniversityProvidenceRIUSA Center for Translational Neuroscience Robert J.and Nancy D.Carney Institute for Brain Science and Brown Institute for Translational ScienceBrown UniversityProvidenceRIUSA

Tropomyosin receptor kinase B(TrkB)signaling plays a pivotal role in dendritic growth and dendritic spine formation to promote learning and *** activity-dependent release of brain-derived neurotrophic factor at synapses binds to pre-or postsynaptic TrkB resulting in the strengthening of synapses,reflected by long-term ***,the association of postsynaptic density protein-95 with TrkB enhances phospholipase Cγ-Ca^(2+)/calmodulin-dependent protein kinaseⅡand phosphatidylinositol 3-kinase-mechanistic target of rapamycin signaling required for long-term *** this review,we discuss TrkB-postsynaptic density protein-95 coupling as a promising strategy to magnify brain-derived neurotrophic factor signaling towards the development of novel therapeutics for specific neurological disorders.A reduction of TrkB signaling has been observed in neurodegenerative disorders,such as Alzheimer's disease and Huntington's disease,and enhancement of postsynaptic density protein-95 association with TrkB signaling could mitigate the observed deficiency of neuronal connectivity in schizophrenia and *** with brain-derived neurotrophic factor is problematic,due to poor pharmacokinetics,low brain penetration,and side effects resulting from activation of the p75 neurotrophin receptor or the truncated TrkB.T1 *** TrkB agonists and antibodies that activate TrkB are being intensively investigated,they cannot distinguish the multiple human TrkB splicing isoforms or cell type-specific *** TrkB–postsynaptic density protein-95 coupling provides an alternative approach to specifically boost TrkB signaling at localized synaptic sites versus global stimulation that risks many adverse side effects.

关键词： Angelman syndrome autism brain-derived neurotrophic factor depression neurodegenerative disorder neurodevelopmental disorder postsynaptic density protein-95 synaptic plasticity TrkB

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难治性原发性胆汁性胆管炎的治疗新进展

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临床肝胆病杂志 2017年第11期33卷 2230-2234页

作者：倪萍凡小丽文茂瑶杨丽四川大学华西医院消化内科成都610041

原发性胆汁性胆管炎(PBC)是一种以小胆管损伤为特点的自身免疫性肝病。熊去氧胆酸(UDCA)是治疗本病的主要药物,但约40%的PBC患者对UDCA生化应答欠佳,预后较差。总结了难治性PBC患者的治疗新选择。2017年,奥贝胆酸已被欧洲肝病学会推荐作... 详细信息

原发性胆汁性胆管炎(PBC)是一种以小胆管损伤为特点的自身免疫性肝病。熊去氧胆酸(UDCA)是治疗本病的主要药物,但约40%的PBC患者对UDCA生化应答欠佳,预后较差。总结了难治性PBC患者的治疗新选择。2017年,奥贝胆酸已被欧洲肝病学会推荐作为UDCA应答不佳PBC的二线治疗药物。贝特类药物或布地奈德联合UDCA治疗难治性PBC的相关研究也取得了一定进展,但其疗效与安全性仍需大样本随机双盲对照试验进一步验证。单克隆抗体、改变胆汁酸生成或重吸收药物等尚处于实验阶段。目前,肝移植仍然是延长终末期PBC患者生存期的唯一治疗方法。

关键词：肝硬化胆汁性治疗综述

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Wave effect of gravitational waves intersected with a microlens field Ⅱ:An adaptive hierarchical tree algorithm and population study

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Science China(Physics,Mechanics & Astronomy) 2025年第1期Mechanics & Astronomy) .卷 241-254页

作者： Xikai Shan Guoliang Li Xuechun Chen wen Zhao Bin Hu Shude Mao Department of Astronomy Tsinghua University Purple Mountain Observatory Chinese Academy of Sciences Institute for Frontier in Astronomy and Astrophysics Beijing Normal University School of Physics and Astronomy Beijing Normal University School of Astronomy and Space Science University of Science and Technology of China CAS Key Laboratory for Researches in Galaxies and Cosmology Department of Astronomy University of Science and Technology of ChinaChinese Academy of Sciences

The gravitational lensing wave effect generated by a microlensing field embedded in a lens galaxy is an inevitable phenomenon in strong lensed gravitational waves （SLGWs）.This effect presents both challenges and opportunities for the detection and application of ***,investigating this wave effect requires computing a complete diffraction integral over each microlens in the *** is extremely time-consuming due to the large number of microlenses （10～3-10～6）.Therefore,simply adding all the microlenses is ***,the complexity of the time delay surface makes the lens plane resolution a crucial factor in controlling numerical *** this paper,we propose a trapezoid approximation-based adaptive hierarchical tree algorithm to meet the challenges of calculation speed and *** find that this algorithm accelerates the calculation by four orders of magnitude compared to the simple adding method and is one order of magnitude faster than the fixed hierarchical tree algorithm proposed for electromagnetic *** importantly,our algorithm ensures controllable numerical errors,increasing confidence in the *** with our previous work （***.66,239511,2023）,this paper addresses all numerical issues,including integral convergence,precision,and computational time1).Finally,we conducted a population study on the microlensing wave effect of SLGWs using this algorithm and found that the microlensing wave effect cannot be ignored,especially for Type II SLGWs （from saddle position of the time delay surface） due to their intrinsic geometric structures and their typical intersection with a denser microlensing ***,more than 33%（11%） of SLGWs have a mismatch larger than 1%（3%） compared to the unlensed ***,we found that the mismatch between signal pairs in a doubly imaged GW is generally larger than 10-3,and 61%（25%） of signal pairs have a mismatch larger than 1%（3%）.Therefo

关键词： gravitational lensing diffractional integral algorithm gravitational wave

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The detection, extraction and parameter estimation of extreme-mass-ratio inspirals with deep learning

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Science China(Physics,Mechanics & Astronomy) 2025年第1期Mechanics & Astronomy) .卷 86-96页

作者： Qianyun Yun wen-Biao Han Yi-Yang Guo He Wang Minghui Du Hangzhou Institute for Advanced Study University of Chinese Academy of Sciences Shanghai Astronomical Observatory Chinese Academy of Sciences School of Physics and Astronomy Shanghai Jiao Tong University School of Astronomy and Space Science University of Chinese Academy of Sciences Taiji Laboratory for Gravitational Wave Universe (Beijing/Hangzhou) University of Chinese Academy of Sciences Lanzhou Center for Theoretical Physics Key Laboratory of Theoretical Physics of Gansu Province Key Laboratory of Quantum Theory and Applications of MoE Lanzhou University Institute of Theoretical Physics & Research Center of Gravitation Lanzhou University International Centre for Theoretical Physics Asia-Pacific (ICTP-AP) University of Chinese Academy of Sciences (UCAS) Center for Gravitational Wave Experiment National Microgravity Laboratory Institute of Mechanics Chinese Academy of Sciences

One of the primary goals of space-borne gravitational wave detectors is to detect and analyze extreme-mass-ratio inspirals(EMRIs). This task is particularly challenging because EMRI signals are complex, lengthy, and faint. In this work, we introduce a2-layer convolutional neural network(CNN) approach to detect EMRI signals for space-borne detectors, achieving a true positive rate(TPR) of 96.9% at a 1% false positive rate(FPR) for signal-to-noise ratio(SNR) from 50 to 100. Especially, the key intrinsic parameters of EMRIs such as the mass, spin of the supermassive black hole(SMBH) and the initial eccentricity of the orbit can also be inferred directly by employing a neural network. The mass and spin of the SMBH can be determined at 99% and 92% respectively. This will greatly reduce the parameter spaces and computing cost for the following Bayesian parameter *** model also has a low dependency on the accuracy of the waveform model. This study underscores the potential of deep learning methods in EMRI data analysis, enabling the rapid detection of EMRI signals and efficient parameter estimation.

关键词： gravitational wave EMRIs deep-learing

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An efficient quantum proactive incremental learning algorithm

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Science China(Physics,Mechanics & Astronomy) 2025年第1期Mechanics & Astronomy) .卷 49-57页

作者： Lingxiao Li Jing Li Yanqi Song Sujuan Qin Qiaoyan wen Fei Gao State Key Laboratory of Networking and Switching Technology Beijing University of Posts and Telecommunications School of Cyberspace Security Beijing University of Posts and Telecommunications

In scenarios where a large amount of data needs to be learned, incremental learning can make full use of old knowledge, significantly reduce the computational cost of the overall learning process, and maintain high performance. In this paper, taking the MaxCut problem as our example, we introduce the idea of incremental learning into quantum computing, and propose a Quantum Proactive Incremental Learning algorithm(QPIL). Instead of a one-off training of quantum circuit, QPIL contains a multi-phase training on gradually-increased subgraphs of all vertices, proactively reducing large-scale problems to smaller ones to solve in steps, providing an efficient solution for MaxCut. Specifically, some vertices and corresponding edges are randomly selected for training to obtain optimized parameters of the quantum circuit at first. Then, in each incremental phase, the remaining vertices and corresponding edges are gradually added and the parameters obtained from the previous phase are reused in the parameter initialization of the current phase. We perform experiments on 120 different small-scale graphs, and it shows that QPIL performs superior to prevalent quantum and classical baselines in terms of approximation ratio(AR), time cost, anti-forgetting, and solving stability. In particular, QPIL's AR surpasses 20% of mainstream quantum baselines, and the time cost is less than 1/5 of them. The idea of QPIL is expected to inspire efficient and high-quality solutions in large-scale Max Cut and other combinatorial optimization problems.

关键词： variational quantum algorithm incremental learning multi-phase training MaxCut quantum computing

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