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Classifying hepatitis B therapies with insights from covalently closed circular DNA dynamics

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Virologica Sinica 2024年第1期39卷 9-23页

作者： Jie-Li hu ai-Long huang Key Laboratory of Molecular Biology on Infectious Diseases Ministry of EducationChongqing Medical UniversityChongqing400016China

The achievement of a functional cure for chronic hepatitis B(CHB)remains limited to a minority of patients treated with currently approved *** primary objective in developing new anti-HBV drugs is to enhance the functional cure rates for CHB.A critical prerequisite for the functional cure of CHB is a substantial reduction,or even eradication of covalently closed circular DNA(cccDNA).Within this context,the changes in cccDNA levels during treatment become as a pivotal *** have previously analyzed the factors influencing cccDNA dynamics and introduced a preliminary classification of hepatitis B treatment strategies based on these *** this review,we employ a systems thinking perspective to elucidate the fundamental aspects of the HBV replication cycle and to rationalize the classification of treatment strategies according to their impact on the dynamic equilibrium of *** upon this foundation,we categorize current anti-HBV strategies into two distinct groups and advocate for their combined use to significantly reduce cccDNA levels within a well-defined timeframe.

关键词： Hepatitis B cccDNA Functional cure Dynamics Treatment Strategy

Twenty-four-hour ambulatory blood pressure changes in older patients with essential hypertension receiving monotherapy or dual combination antihypertensive drug therapy

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Journal of Geriatric Cardiology 2019年第4期16卷 354-361页

作者： Pei-Pei LU Xu MENG Ying ZHANG Yan-Qi LI Shu WANG Li-Sheng LIU Wen WANG Yu-Ling LI Yu-Qing ZHANG ai-hua hu Xian-Liang ZHOU Li-Hong MA Department of Cardiology Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Science and Peking Union Medical CollegeBeijingChina Clinical Trial and Research Center Beijing Hypertension League InstituteChinese Hypertension LeagueBeijingChina Xinjiekou Community Health Service Center BeijingChina Department of Traditional Chinese Medicine Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

Objective To evaluate the differences in 24-hour ambulatory blood pressure (BP) in older patients with hypertension treated with the five major classes of antihypertensive drugs,as monotherapy or dual combination therapy,to improve daytime and nighttime BP control. Methods We enrolled 1920 Chinese community-dwelling outpatients aged ≥ 60 years and compared ambulatory BP values and ambulatory BP control (24-hour BP < 130/80 mmHg;daytime mean BP < 135/85 mmHg;and nighttime mean BP < 120/70 mmHg),as well as nighttime BP dip patterns for monotherapy and dual combination therapy groups. Results Patients’ mean age was 71 years,and 59.5% of patients were women. Calcium channel blockers (CCBs) constituted the most common (60.3% of patients) monotherapy,and renin–angiotensin system (RAS) blockers combined with CCBs was the most common (56.5% of patients) dual combination therapy. Monotherapy with beta-blockers (BB) provided the best daytime BP control. The probabilities of having a nighttime dip pattern and nighttime BP control were higher in patients receiving diuretics compared with CCBs (OR = 0.52,P = 0.05 and OR = 0.41,P = 0.007,respectively). Patients receiving RAS/diuretic combination therapy had a higher probability of having controlled nighttime BP compared with those receiving RAS/CCB (OR = 0.45,P = 0.004). Compared with RAS/diuretic therapy,BB/CCB therapy had a higher probability of achieving daytime BP control (OR = 1.27,P = 0.45). Conclusions Antihypertensive monotherapy and dual combination drug therapy provided different ambulatory BP control and nighttime BP dip patterns. BB-based regimens provided lower daytime BP,whereas diuretic-based therapies provided lower nighttime BP,compared with other antihypertensive regimens.

关键词： Aging Ambulatory blood pressure monitoring Antihypertensive drugs Beta-blockers Diuretics

Color coded metadevices toward programmed terahertz switching

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Light(Science & Applications) 2024年第7期13卷 1383-1392页

作者： Weibao He Xiang’ai Cheng Siyang hu Ziheng Ren Zhongyi Yu Shun Wan Yuze hu Tian Jiang College of Advanced Interdisciplinary Studies National University of Defense TechnologyChangshaChina. Nanhu Laser Laboratory National University of Defense TechnologyChangshaChina. hunan Provincial Key Laboratory of High Energy Laser Technology National University of Defense TechnologyChangshaChina. Institute for Quantum Science and Technology College of ScienceNational University of Defense TechnologyChangshaChina

Terahertz modulators play a critical role in high-speed wireless communication,non-destructive imaging,and so on,which have attracted a large amount of research ***,all-optical terahertz modulation,an ultrafast dynamical control approach,remains to be limited in terms of encoding and *** we experimentally demonstrated an optical-programmed terahertz switching realized by combining optical metasurfaces with the terahertz metasurface,resulting in 2-bit dual-channel terahertz *** terahertz metasurface,made up of semiconductor islands and artificial microstructures,enables effective all-optical programming by providing multiple frequency channels with ultrafast modulation at the nanosecond ***,optical metasurfaces covered in terahertz metasurface alter the spatial light field distribution to obtain color *** to the time-domain coupled mode theory analysis,the energy dissipation modes in terahertz metasurface can be independently controlled by color excitation,which explains the principle of 2-bit encoding *** work establishes a platform for all-optical programmed terahertz metadevices and may further advance the application of composite metasurface in terahertz manipulation.

关键词： terahertz surface excitation

Emergence of SARS and COVID-19 and preparedness for the next emerging disease X

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Frontiers of Medicine 2024年第1期18卷 1-18页

作者： Ben hu hua Guo Haorui Si Zhengli Shi CAS Key Laboratory of Special Pathogens and Biosafety Wuhan Institute of VirologyChinese Academy of SciencesWuhan430071China University of Chinese Academy of Sciences Beijing100049China

Severe acute respiratory syndrome(SARS)and Coronavirus disease 2019(COVID-19)are two human Coronavirus diseases emerging in this century,posing tremendous threats to public health and causing great loss to lives and *** this review,we retrospect the studies tracing the molecular evolution of SARS-CoV,and we sort out current research findings about the potential ancestor of *** knowledge about SARS-CoV-2-like viruses found in wildlife,the animal susceptibility to SARS-CoV-2,as well as the interspecies transmission risk of SARS-related coronaviruses(SARSr-CoVs)are gathered ***,we discuss the strategies of how to be prepared against future outbreaks of emerging or re-emerging coronaviruses.

关键词： SARS COVID-19 coronavirus

Different El Niño Flavors and Associated Atmospheric Teleconnections as Simulated in a Hybrid Coupled Model

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Advances in Atmospheric Sciences 2024年第5期41卷 864-880页

作者： Junya hu Hongna WANG Chuan GAO Rong-hua ZHANG Key Laboratory of Ocean Circulation and Waves Institute of Oceanologyand Center for Ocean Mega-ScienceChinese Academy of SciencesQingdao 266071China School of Marine Sciences Nanjing University of Information Science and TechnologyNanjing 210044China Laoshan Laboratory Qingdao 266237China

A previously developed hybrid coupled model(HCM)is composed of an intermediate tropical Pacific Ocean model and a global atmospheric general circulation model(AGCM),denoted as *** this study,different El Niño flavors,namely the Eastern-Pacific(EP)and Central-Pacific(CP)types,and the associated global atmospheric teleconnections are examined in a 1000-yr control simulation of the *** HCMAGCM indicates profoundly different characteristics among EP and CP El Niño events in terms of related oceanic and atmospheric variables in the tropical Pacific,including the amplitude and spatial patterns of sea surface temperature(SST),zonal wind stress,and precipitation *** SST budget analysis indicates that the thermocline feedback and zonal advective feedback dominantly contribute to the growth of EP and CP El Niño events,*** to the shifts in the tropical rainfall and deep convection during EP and CP El Niño events,the model also reproduces the differences in the extratropical atmospheric responses during the boreal *** particular,the EP El Niño tends to be dominant in exciting a poleward wave train pattern to the Northern Hemisphere,while the CP El Niño tends to preferably produce a wave train similar to the Pacific North American(PNA)*** a result,different climatic impacts exist in North American regions,with a warm-north and cold-south pattern during an EP El Niño and a warm-northeast and cold-southwest pattern during a CP El Niño,*** modeling result highlights the importance of internal natural processes within the tropical Pacific as they relate to the genesis of ENSO diversity because the active ocean–atmosphere coupling is allowed only in the tropical Pacific within the framework of the HCMAGCM.

关键词： hybrid coupled model tropical Pacific Ocean global atmosphere Eastern/Central-Pacific El Niño atmospheric teleconnections

A two-pronged strategy utilizing exosomes extracted from antigenpresenting cells to combat hepatitis B

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Nano Research 2024年第10期17卷 9084-9094页

作者： Fumin hu Dangyang Wang Ting Lu Guanghui Ma hua Yue State Key Laboratory of Biochemical Engineering Institute of Process EngineeringChinese Academy of SciencesBeijing 100190China University of Chinese Academy of Sciences Beijing 100049China Key Laboratory of Biopharmaceutical Preparation and Delivery Chinese Academy of SciencesBeijing 100190China

Chronic hepatitis B(CHB)is consistently challenging to conquer with numerous complications and *** the effectiveness of antiviral therapies in suppressing hepatitis B virus(HBV)replication,there is an urgent need for novel and more effective treatment *** strategies predominantly emphasize immune activation but still face challenges in sufficiently eliciting T cell *** into account the targeted delivery of nanoparticles to the liver and spleen via intravenous injection,we have proposed a dual-pronged therapeutic strategy based on antigen-presenting cells(APCs)-derived ***,exosomes targeted to the spleen can activate specific immune responses,while those targeted to the liver can modulate or reverse the liver’s immunosuppressive *** immunization,exosome formulations exhibit the remarkable ability to effectively activate APCs,thereby triggering the proliferation of CD8^(+)T ***,they also play an immunoregulatory role by converting M2 macrophages into M1 *** two-pronged therapeutic strategy precisely addresses the issues of T cell dysfunction and immune suppression,both characteristic features of CHB *** combined with Aluminum(Alum)-adjuvanted vaccine,these exosome formulations not only demonstrate a high level of cellular immune response but also secrete specific antibodies comparable to those induced by Alum *** combined approach effectively enhances both cellular and humoral immunity,offering a promising avenue for the development of therapeutic hepatitis B vaccines based on exosome formulations.

关键词： chronic hepatitis B antigen-presenting cells(APCs)-derived exosomes immunoregulatory role two-pronged therapeutic strategy

Synergistic Interdecadal Evolution of Precipitation over Eastern China and the Pacific Decadal Oscillation during 1951-2015

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Advances in Atmospheric Sciences 2024年第1期41卷 53-72页

作者： Minmin WU Rong-hua ZHANG Junya hu Hai ZHI Key Laboratory of Ocean Circulation and Waves Institute of OceanologyChinese Academy of SciencesQingdao 266071China School of Marine Sciences Nanjing University of Information Science and TechnologyNanjing 210044China Laosan Laboratory Qingdao 266237China School of Atmospheric Sciences Nanjing University of Information Science and TechnologyNanjing 210044China University of Chinese Academy of Sciences Beijing 100029China

By using the multi-taper method(MTM)of singular value decomposition(SVD),this study investigates the interdecadal evolution(10-to 30-year cycle)of precipitation over eastern China from 1951 to 2015 and its relationship with the North Pacific sea surface temperature(SST).Two significant interdecadal signals,one with an 11-year cycle and the other with a 23-year cycle,are identified in both the precipitation and SST *** show that the North Pacific SST forcing modulates the precipitation distribution over China through the effects of the Pacific Decadal Oscillation(PDO)-related anomalous Aleutian low on the western Pacific subtropical high(WPSH)and Mongolia high(MH).During the development stage of the PDO cold phase associated with the 11-year cycle,a weakened WPSH and MH increased the precipitation over the Yangtze River Basin,whereas an intensified WPSH and MH caused the enhanced rain band to move northward to North China during the decay *** the development stage of the PDO cold phase associated with the 23-year cycle,a weakened WPSH and MH increased the precipitation over North China,whereas an intensified WPSH and the weakened MH increased the precipitation over South China during the decay *** 11-year and 23-year variabilities contribute differently to the precipitation variations in the different regions of China,as seen in the 1998flooding *** 11-year cycle mainly accounts for precipitation increases over the Yangtze River Basin,while the 23-year cycle is responsible for the precipitation increase over Northeast *** results have important implications for understanding how the PDO modulates the precipitation distribution over China,helping to improve interdecadal climate prediction.

关键词： MTM-SVD PDO SST anomalies interdecadal variability precipitation over China

Construction and validation of a neovascular glaucoma nomogram in patients with diabetic retinopathy after pars plana vitrectomy

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World Journal of Diabetes 2024年第4期15卷 654-663页

作者： Yi Shi Yan-Xin Zhang Ming-Fei Jiao Xin-Jun Ren Bo-Jie hu ai-hua Liu Xiao-Rong Li Surgical Retina Tianjin Key Laboratory of Retinal Functions and DiseasesTianjin Branch of National Clinical Research Center for Ocular DiseaseEye Institute and School of OptometryTianjin Medical University Eye HospitalTianjin 300384China Glaucoma Tianjin Key Laboratory of Retinal Functions and DiseasesTianjin Branch of National Clinical Research Center for Ocular DiseaseEye Institute and School of OptometryTianjin Medical University Eye HospitalTianjin 300384China Ocular Trauma Tianjin Key Laboratory of Retinal Functions and DiseasesTianjin Branch of National Clinical Research Center for Ocular DiseaseEye Institute and School of OptometryTianjin Medical University Eye HospitalTianjin 300384China

BACKGROUND Neovascular glaucoma(NVG)is likely to occur after pars plana vitrectomy(PPV)for diabetic retinopathy(DR)in some patients,thus reducing the expected *** the risk factors for NVG occurrence and building effective risk prediction models are currently required for clinical *** To develop a visual risk profile model to explore factors influencing DR after *** We retrospectively selected 151 patients with DR undergoing *** patients were divided into the NVG(NVG occurrence)and No-NVG(No NVG occurrence)groups according to the occurrence of NVG within 6 months after *** risk factors for postoperative NVG were screened by logistic regression.A nomogram prediction model was established using R software,and the model’s prediction accuracy was verified internally and externally,involving the receiver operator characteristic curve and correction *** After importing the data into a logistic regression model,we concluded that a posterior capsular defect,preoperative vascular endothelial growth factor≥302.90 pg/mL,glycosylated hemoglobin≥9.05%,aqueous fluid interleukin 6(IL-6)≥53.27 pg/mL,and aqueous fluid IL-10≥9.11 pg/mL were independent risk factors for postoperative NVG in patients with DR(P<0.05).A nomogram model was established based on the aforementioned independent risk factors,and a computer simulation repeated sampling method was used to internally and externally verify the nomogram *** area under the curve(AUC),sensitivity,and specificity of the model were 0.962[95%confidence interval(95%CI):0.932-0.991],91.5%,and 82.3%,*** AUC,sensitivity,and specificity of the external validation were 0.878(95%CI:0.746-0.982),66.7%,and 95.7%,*** A nomogram constructed based on the risk factors for postoperative NVG in patients with DR has a high prediction *** study can help formulate relevant preventive and treatment measures.

关键词： Diabetic retinopathy Retinopathy Neovascular Glaucoma Risk factors Nomogram

Clinical Analysis and Mental Health Survey of Hemophilia Carriers:a Cross-sectional Study

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Current Medical Science 2024年第2期44卷 435-440页

作者： Wen WANG Li-juan JIANG Dong-yan CUI ai ZHANG Xiong WANG ai-guo LIU Qun hu Department of Pediatrics Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Laboratory Medicine Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

Objective:Hemophilia carriers(HCs),who are heterozygous for mutations in the clotting factor VIII/clotting factor IX gene(F8 or F9),may have a wide range of clotting factor levels,from very low,similar to afflicted males,to the upper limit of normal,and may experience mental health *** purpose of this study was to provide genetic information on mothers of hemophilia patients and to understand the clotting factor activity and phenotype of ***,we aimed to investigate the mental health status of HCs in ***:A total of 127 hemophilia mothers,including 93 hemophilia A(HA)mothers and 34 hemophilia B(HB)mothers,were enrolled in this *** distance PCR,multiplex PCR,and Sanger sequencing were used to analyze mutations in F8 or *** factor activity was detected by a one-stage clotting *** Symptom Checklist 90(SCL-90,China/Mandarin version)was given to HCs at the same time to assess their mental ***:A total of 90.6%of hemophilia mothers were diagnosed genetically as carriers,with inversion in intron 22 and missense mutations being the most common mutation types in HA and HB carriers,*** median clotting factor level in carriers was 0.74 IU/mL(ranging from 0.09 to 1.74 IU/mL)compared with 1.49 IU/mL(ranging from 0.93 to 1.89 IU/mL)in noncarriers,of which 14.3%of HCs had clotting factor levels of 0.40 IU/mL or below.A total of 53.8%(7/13)of HA carriers with low clotting factor levels(less than 0.50 IU/mL)had a history of bleeding,while none of the HB carriers displayed a bleeding *** total mean score and the global severity index of the SCL-90 for surveyed HCs were 171.00(±60.37)and 1.78(±0.59),respectively.A total of 67.7%of the respondents had psychological symptoms,with obsessive-compulsive disorder being the most prevalent and *** pooled estimates of all nine factors were significantly higher than those in the general population(P<0.05).Conclusions:The detection rate of gene mutations

关键词： hemophilia A hemophilia B mutation carrier mental health