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Reactive oxygen species and nitric oxide scavenging nanoparticles alleviating rheumatoid arthritis through adjusting the seeds and growing soils

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Acta Pharmaceutica Sinica B 2023年第12期13卷 5016-5029页

作者： Peng Hua Ruifeng Liang Yanbei Tu Yuying Yin man-kay law Meiwan Chen State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao SARChina State Key Laboratory of Analog and Mixed-Signal VLSI IME and FST-ECEUniversity of MacaoMacao SARChina

Normalizing inflamed soils including reactive oxygen species(ROS),nitric oxide(NO),cellfree DNA,and regulating infammation-related seeds such as macrophages,neutrophils,fibroblasts,represent a promising strategy to maintain synovial tissue homeostasis for rheumatoid arthritis(RA)***,ROS scavenging amphiphilic block copolymer PEGylated bilirubin and NO-scavenging PEGylated o-phenylenediamine were fabricated to self-assemble into a dually responsive nanoparticle loaded with JAK inhibitor notopterol(Not@BR/oPDA-PEG,NBOP NPs).The simultaneous ROS and NO depletion combined with JAK-STAT pathway inhibition could not only promote M2 polarization to reduce further ROS and NO generation,but also decrease cytokines and chemokines to prevent immune cell ***,NBOP NPs responded to high level ROS and NO,and disintegrated to release notopterol in inflamed joints as the hydrophobic heads BR and oPDA were transformed into hydrophilic *** released notopterol could inhibit the JAK-STAT pathway of infammatory cells to reduce the secretion of pro-inflammatory cytokines and *** strategy represented an effective way to regulate RA soils and seeds through breaking the positive feedback loop of inflammation aggravation,achieving an excellent anti-RA efficacy in a collagen-induced arthritis rat *** together,our work offered a reference to adjust RA soils and seeds for enhanced RA treatment.

关键词： Bilirubin o-Phenylenediamine Notopterol ROS and NO scavenging JAK-STATpathway Anti-inflammatory Cartilage protection Rheumatoid arthritis

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Effects of SARS-CoV-2 infection on incidence and treatment strategies of hepatocellular carcinoma in people with chronic liver disease

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World Journal of Hepatology 2024年第2期16卷 211-228页

作者： Lung-Yi Mak Matthew Shing Hin Chung Xue Li Francisco Tsz Tsun Lai Eric Yuk Fai Wan Celine Sze Ling Chui Franco Wing Tak Cheng Esther Wai Yin Chan Ching Lung Cheung Ivan Chi Ho Au Xi Xiong Wai-kay Seto man-Fung Yuen Carlos King Ho Wong Ian Chi Kei Wong Department of Medicine The University of Hong KongHong KongChina State Key Laboratory of Liver Research The University of Hong KongHong KongChina Department of Pharmacology and Pharmacy The University of Hong KongHong KongChina Laboratory of Data Discovery for Health(D24H) Hong Kong Science and Technology ParkHong KongChina Department of Family Medicine and Primary Care The University of Hong KongHong KongChina School of Nursing The University of Hong KongHong KongChina School of Public Health The University of Hong KongHong KongChina Research Department of Practice and Policy University College LondonLondon WC1E 6BTUnited Kingdom Aston School of Pharmacy Aston UniversityBirmingham B47ETUnited Kingdom

BACKGROUND Chronic liver disease(CLD)was associated with adverse clinical outcomes among people with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)*** To determine the effects of SARS-CoV-2 infection on the incidence and treatment strategy of hepatocellular carcinoma(HCC)among patients with *** A retrospective,territory-wide cohort of CLD patients was identified from an electronic health database in Hong *** with confirmed SARS-CoV-2 infection[coronavirus disease 2019(COVID-19)+CLD]between January 1,2020 and October 25,2022 were identified and matched 1:1 by propensity-score with those without(COVID-19-CLD).Each patient was followed up until death,outcome event,or November 15,*** outcome was incidence of *** outcomes included all-cause mortality,adverse hepatic outcomes,and different treatment strategies to HCC(curative,non-curative treatment,and palliative care).Analyses were further stratified by acute(within 20 d)and post-acute(21 d or beyond)phases of SARS-CoV-2 *** rate ratios(IRRs)were estimated by Poisson regression *** Of 193589 CLD patients(>95%non-cirrhotic)in the cohort,55163 patients with COVID-19+CLD and 55163 patients with COVID-19-CLD were included after 1:1 propensity-score *** 249-d median follow-up,COVID-19+CLD was not associated with increased risk of incident HCC(IRR:1.19,95%CI:0.99-1.42,P=0.06),but higher risks of receiving palliative care for HCC(IRR:1.60,95%CI:1.46-1.75,P<0.001),compared to *** both acute and post-acute phases of infection,COVID-19+CLD were associated with increased risks of allcause mortality(acute:IRR:7.06,95%CI:5.78-8.63,P<0.001;post-acute:IRR:1.24,95%CI:1.14-1.36,P<0.001)and adverse hepatic outcomes(acute:IRR:1.98,95%CI:1.79-2.18,P<0.001;post-acute:IRR:1.24,95%CI:1.13-1.35,P<0.001),compared to *** Although CLD patients with SARS-CoV-2 infection were not associated with increased risk of HCC,they

关键词： SARS-CoV-2 infection Chronic liver disease Long COVID Post-COVID-19 syndrome Cirrhosis Hepatocellular carcinoma

基于MK-LSTM算法的盾构掘进参数相关性分析及结构变形预测

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吉林大学学报（工学版） 2024年第6期54卷 1624-1633页

作者：陈城史培新贾鹏蛟董曼曼苏州大学轨道交通学院江苏苏州215000 东北大学资源与土木工程学院辽宁沈阳110819 常熟理工学院江苏苏州215506

提出了MIC-K-median-LSTM(MK-LSTM)算法,用于对盾构掘进过程进行参数相关性分析和结构变形预测。首先,运用改进的MIC(MK)算法对涉及盾构掘进过程中的各参数与结构变形进行相关性分析;然后,在得到相关系数的基础上提出输入参数的修正方法... 详细信息

提出了MIC-K-median-LSTM(MK-LSTM)算法,用于对盾构掘进过程进行参数相关性分析和结构变形预测。首先,运用改进的MIC(MK)算法对涉及盾构掘进过程中的各参数与结构变形进行相关性分析;然后,在得到相关系数的基础上提出输入参数的修正方法;最后,通过LSTM模型对不同维度输入参数的预测效果进行分析,确定合理的输入参数维度。结果表明:盾构参数对既有结构变形的影响大于土体参数;MK算法可以有效降低计算复杂度和减小噪声对数据的影响,基于参数相关系数的数据前处理方法有利于提高模型的预测精度;MK-LSTM可以有效预测结构随时间的变形规律,考虑数据维度对预测精度的提升效果和计算效率的影响,进行实际工程预测时可以根据参数相关性大小进行维度删减。

关键词：盾构隧道机器学习参数维度参数相关性变形

Transfusion-transmitted hepatitis E:What we know so far?

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World Journal of Gastroenterology 2022年第1期28卷 47-75页

作者： Carmen Ka man Cheung Sunny Hei Wong Alvin Wing Hin law man Fai law Medicine and Therapeutics Prince of Wales HospitalHong Kong 852China Institute of Digestive Disease and Department of Medicine and Therapeutics the Chinese University of Hong KongHong Kong 852China Lee Kong Chian School of Medicine Nanyang Technological UniversitySingapore 639798Singapore West Island School Hong Kong 852China

Hepatitis E virus(HEV)is a major cause of viral hepatitis *** is growing concern about transfusion-transmitted HEV(TT-HEV)as an emerging global health *** can potentially result in chronic infection in immunocompromised patients,leading to a higher risk of liver cirrhosis and even *** 0.0013%and 0.281%of asymptomatic blood donors around the world have HEV viremia,and 0.27%to 60.5%have anti-HEV immunoglobulin *** is infectious even at very low blood concentrations of the *** patients who develop persistent hepatitis E infection should have their immunosuppressant regimen reduced;ribavirin may be considered as *** interferon can be considered in those who are refractory or intolerant to ***,a nucleotide analog,showed modest antiviral activity in some clinical studies but sustained viral response was not ***,rescue treatment remains an unmet *** need for HEV screening of all blood donations remains *** screening has been adopted in some countries after consideration of risk and resource *** pathogen reduction methods have also been proposed to reduce the risk of *** studies are needed to define the incidence of transmission through transfusion,their clinical features,outcomes and prognosis.

关键词： Hepatitis E virus Acute and chronic hepatitis Immunosuppression Blood transfusion Transplantation

Efficacy of Vaccine Protection Against COVID-19 Virus Infection in Patients with Chronic Liver Diseases

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Journal of Clinical and Translational Hepatology 2023年第3期11卷 718-735页

作者： Carmen Ka man Cheung Kimmy Wan Tung law Alvin Wing Hin law man Fai law Rita Ho Sunny Hei Wong Department of Medicine and Therapeutics Prince of Wales HospitalHong KongChina West Island School Hong KongChina Department of Medicine North District HospitalHong KongChina Institute of Digestive Disease and Department of Medicine and Therapeutics State Key Laboratory of Digestive DiseaseLi Ka Shing Institute of Health SciencesThe Chinese University of Hong KongHong KongChinaLee Kong Chian School of MedicineNanyang Technological UniversitySingapore

The outbreak of coronavirus disease 2019 (COVID-19) has resulted in significant morbidity and mortality worldwide. Vaccination against coronavirus disease 2019 is a use-ful weapon to combat the virus. Patients with chronic liver diseases (CLDs), including compensated or decompensated liver cirrhosis and noncirrhotic diseases, have a decreased immunologic response to coronavirus disease 2019 vaccines. At the same time, they have increased mortality if infected. Current data show a reduction in mortality when patients with chronic liver diseases are vaccinated. A suboptimal vac-cine response has been observed in liver transplant recipi-ents, especially those receiving immunosuppressive therapy, so an early booster dose is recommended to achieve a better protective effect. Currently, there are no clinical data com-paring the protective efficacy of different vaccines in patients with chronic liver diseases. Patient preference, availability of the vaccine in the country or area, and adverse effect profiles are factors to consider when choosing a vaccine. There have been reports of immune-mediated hepatitis after coronavi-rus disease 2019 vaccination, and clinicians should be aware of that potential side effect. Most patients who developed hepatitis after vaccination responded well to treatment with prednisolone, but an alternative type of vaccine should be considered for subsequent booster doses. Further prospec-tive studies are required to investigate the duration of immu-nity and protection against different viral variants in patients with chronic liver diseases or liver transplant recipients, as well as the effect of heterologous vaccination.

关键词： COVID-19 SARS-CoV-2 Chronic liver disease Liver transplanta-tion Vaccine mRNA.

Prevention and management of hepatitis B virus reactivation in patients with hematological malignancies in the targeted therapy era

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世界胃肠病学杂志:英文版 2023年第33期29卷 4942-4961页

作者： Joyce Wing Yan Mak Alvin Wing Hin law Kimmy Wan Tung law Rita Ho Carmen Ka man Cheung man Fai law Department of Medicine and Therapeutics Prince of Wales HospitalHong Kong 852China West Island School Hong Kong 852China Department of Medicine North District HospitalHong Kong 852China

Hepatitis due to hepatitis B virus(HBV)reactivation can be serious and potentially fatal,but is *** reactivation is most commonly reported in patients receiving chemotherapy,especially rituximab-containing therapy for hematological malignancies and those receiving stem cell *** with inactive and even resolved HBV infection still have persistence of HBV genomes in the *** expression of these silent genomes is controlled by the immune *** or ablation of immune cells,most importantly B cells,may lead to reactivation of seemingly resolved HBV ***,all patients with hematological malignancies receiving anticancer therapy should be screened for active or resolved HBV infection by blood tests for hepatitis B surface antigen(HBsAg)and antibody to hepatitis B core *** found to be positive for HBsAg should be given prophylactic antiviral *** patients with resolved HBV infection,there are two *** first is pre-emptive therapy guided by serial HBV DNA monitoring,and treatment with antiviral therapy as soon as HBV DNA becomes *** second approach is prophy-lactic antiviral therapy,particularly for patients receiving high-risk therapy,especially anti-CD20 monoclonal antibody or hematopoietic stem cell *** and tenofovir are the preferred antiviral *** new effective therapies for hematological malignancies have been introduced in the past decade,for example,chimeric antigen receptor(CAR)-T cell therapy,novel monoclonal antibodies,bispecific antibody drug conjugates,and small molecule inhibitors,which may be associated with HBV *** there is limited evidence to guide the optimal preventive measures,we recommend antivi-ral prophylaxis in HBsAg-positive patients receiving novel treatments,including Bruton’s tyrosine kinase inhibitors,B-cell lymphoma 2 inhibitors,and CAR-T cell *** studies are needed to determine the risk o

关键词： Hepatitis B Hematologic neoplasms Chimeric antigen receptor-T cell therapy Monoclonal antibodies Bruton’s tyrosine kinase inhibitors Antiviral agents

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我国数字经济营商环境的内在机理与优化策略

学术前沿 2024年第14期 106-111页

作者：满艺娜对外经济贸易大学法学院

数字经济营商环境强调立法的可适配性、监管理念的包容性、监管方式的创新性、监管能力的协同性。对全国36个城市数字经济营商环境评估结果表明,目前仍存在精准化立法缺失、协同化监管不足、包容审慎监管与法治难以匹配等问题。进一步... 详细信息

数字经济营商环境强调立法的可适配性、监管理念的包容性、监管方式的创新性、监管能力的协同性。对全国36个城市数字经济营商环境评估结果表明,目前仍存在精准化立法缺失、协同化监管不足、包容审慎监管与法治难以匹配等问题。进一步优化数字经济营商环境,应秉持安全与效率一体两翼的监管思路,通过科学立法、创新执法的方式,提升法治化协同监管模式。协调数字经济、数字社会与数字政府的发展,不断做强做优做大我国数字经济。

关键词：数字经济营商环境评估优化策略

固溶处理对选区激光融化316L不锈钢晶间腐蚀性能行为的影响机制

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工程科学学报 2024年第6期46卷 1077-1088页

作者：王保山商强满成中国海洋大学材料科学与工程学院青岛266100

选区激光融化316L不锈钢(SLM-316L不锈钢)常采用固溶处理进行组织优化、消减残余应力,以获得优异综合性能.奥氏体不锈钢的晶间腐蚀行为与其组织结构有较高的依赖性,因此固溶处理会提高SLM-316L不锈钢的晶间腐蚀性能.然而,固溶处理对SLM-... 详细信息

选区激光融化316L不锈钢(SLM-316L不锈钢)常采用固溶处理进行组织优化、消减残余应力,以获得优异综合性能.奥氏体不锈钢的晶间腐蚀行为与其组织结构有较高的依赖性,因此固溶处理会提高SLM-316L不锈钢的晶间腐蚀性能.然而,固溶处理对SLM-316L不锈钢晶间腐蚀行为的影响规律和机制目前尚不清晰.基于此,本文首先对SLM-316L不锈钢进行1150℃固溶处理,随后采用SEM、EBSD、TEM等分析其组织结构特征和纳米氧化物颗粒形貌,最后采用双环电化学再活化和过硫酸铵电解试验研究其晶间腐蚀行为.主要结论如下:固溶处理后SLM-316L不锈钢发生再结晶,形成规则形状等轴晶粒及退火孪晶;纳米氧化物颗粒粗化,晶界处最大尺寸能够达到微米级,同时氧化物颗粒的类型也从菱矿石结构的MnSiO_(3)转变为尖晶石结构CrMn_(2)O_(4);固溶处理导致SLM-316L不锈钢晶间腐蚀性能下降,伴随着敏化时间的延长,晶间腐蚀类型从台阶状转变为沟状.

关键词：晶间腐蚀选区激光融化 316L不锈钢热处理组织结构

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地热储层岩体粗糙裂隙的热流耦合效应研究

哈尔滨工程大学学报 2024年第5期45卷 852-862页

作者：刘先珊李宇李满杨欣重庆大学土木工程学院重庆400045

为了解决地热开采涉及复杂的多物理场耦合问题,提高开采效率,本文针对开采过程中的渗流-传热问题以离散元软件3DEC构建岩体粗糙裂隙热-流耦合数值模型。考虑不同三维形貌特征的岩体裂隙,模拟水力开度为19.17μm在不同流速时的水-岩温度... 详细信息

为了解决地热开采涉及复杂的多物理场耦合问题,提高开采效率,本文针对开采过程中的渗流-传热问题以离散元软件3DEC构建岩体粗糙裂隙热-流耦合数值模型。考虑不同三维形貌特征的岩体裂隙,模拟水力开度为19.17μm在不同流速时的水-岩温度变化规律。结果表明:由于裂隙形貌的阻滞作用,粗糙面出水口温度下降较慢,出水口温度有所上升,模型达到稳态所需的时间随流速和对流换热系数的增大而减小。裂隙形貌对流体和岩体温度分布均有影响,粗糙裂隙面的冷锋形态和裂隙面的形貌密切相关。光滑裂隙热突破快于粗糙裂隙,增加裂隙面的粗糙度有助于延长热突破时间。粗糙裂隙面相对于光滑裂隙面的总热量提取率略有提升,流速和对流换热系数的增加显著提高总热量提取率。通过本文研究可以为地热能系统的设计提供重要参数和指导,能够提高地热能开发利用效率。

关键词：干热岩渗流-传热三维形貌水力开度流速对流换热系数粗糙裂隙面热采率热突破

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