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Effects of 17-allylamino-17-demethoxygeldanamycin (17-AAG) in transgenic mouse models of frontotemporal lobar degeneration and Alzheimer’s disease

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Translational Neurodegeneration 2013年第1期2卷 174-182页

作者： Shuk Wai Ho Yuk Tung Chanel Tsui ting ting wong Stanley Kwok-Kuen Cheung William B Goggins Lau Ming Yi Kwok Kin Cheng Larry Baum Department of Surgery The University of Hong KongPokfulamHong KongChina School of Biomedical Sciences(Pharmacology) The University of NottinghamNottinghamUK Department of Microbiology The University of Hong KongPokfulamHong KongChina School of Public Health and Primary Care The Chinese University of Hong KongShatinHong KongChina School of Pharmacy The Chinese University of Hong KongShatinHong KongChina

Alzheimer’s disease(AD),the most common dementia,is characterized by potentially neurotoxic aggregation of Aβ peptide and tau protein,and their deposition as amyloid plaques and neurofibrillary tangles(NFTs).Tau aggregation also occurs in other common neurodegenerative diseases.Frontotemporal dementia(FTD)can be caused by tau mutations that increase the susceptibility of tau to hyperphosphorylation and aggregation,which may cause neuronal dysfunction and deposition of NFTs.17-allylamino-17-demethoxygeldanamycin(17-AAG)is a potent inhibitor of heat shock protein 90(Hsp90),a cytosolic chaperone implicated in the proper folding and functions of a repertoire of client proteins.17-AAG binds to Hsp90 and enhances degradation of Hsp90 client protein.We sought to determine whether 17-AAG can reduce Aβ and tau pathology in the brains of AD and FTD model mice expressing Aβ or P301L mutant tau,respectively.Mice were randomized to receive 25,5,or 0 mg/kg 17-AAG thrice weekly from age eight to 11 months.Analysis was performed by rotarod test on motor function,on the area occupied by plaques in hippocampus or NFTs in medulla tissue sections,and on mortality.A high dose of 17-AAG tended to decrease NFTs in male mice(p=0.08).Further studies are required to confirm the effect of 17-AAG in diseases of tau aggregation.

关键词： Dementia Mouse Tangles Plaques

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Application of artifcial intelligence in cataract management:current and future directions

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Eye and Vision 2024年第1期10卷 21-30页

作者： Laura Gutierrez Jane Sujuan Lim Li Lian Foo Wei Yan Ng Michelle Yip Gilbert Yong San Lim Melissa Hsing Yi wong Allan Fong Mohamad Rosman Jodhbir Singth Mehta Haotian Lin Darren Shu Jeng ting Daniel Shu Wei ting Singapore Eye Research Institute SingaporeSingapore Singapore National Eye Center 11 Third Hospital AvenueSingapore 168751Singapore Academic Ophthalmology School of MedicineUniversity of NottinghamNottinghamUK Zhongshan Ophthalmic Center Sun Yet Sen UniversityGuangzhouChina

The rise of artifcial intelligence(AI)has brought breakthroughs in many areas of medicine.In ophthalmology,AI has delivered robust results in the screening and detection of diabetic retinopathy,age-related macular degeneration,glaucoma,and retinopathy of prematurity.Cataract management is another feld that can beneft from greater AI application.Cataract is the leading cause of reversible visual impairment with a rising global clinical burden.Improved diagnosis,monitoring,and surgical management are necessary to address this challenge.In addition,patients in large developing countries often sufer from limited access to tertiary care,a problem further exacerbated by the ongoing COVID-19 pandemic.AI on the other hand,can help transform cataract management by improving automation,efcacy and overcoming geographical barriers.First,AI can be applied as a telediagnostic platform to screen and diagnose patients with cataract using slit-lamp and fundus photographs.This utilizes a deep-learning,convolutional neural network(CNN)to detect and classify referable cataracts appropriately.Second,some of the latest intraocular lens formulas have used AI to enhance prediction accuracy,achieving superior postoperative refractive results compared to traditional formulas.Third,AI can be used to augment cataract surgical skill training by identifying diferent phases of cataract surgery on video and to optimize operating theater workfows by accurately predicting the duration of surgical procedures.Fourth,some AI CNN models are able to efectively predict the progression of posterior capsule opacifcation and eventual need for YAG laser capsulotomy.These advances in AI could transform cataract management and enable delivery of efcient ophthalmic services.The key challenges include ethical management of data,ensuring data security and privacy,demonstrating clinically acceptable performance,improving the generalizability of AI models across heterogeneous populations,and improving the trust of end-users.

关键词： Artifcial intelligence Telemedicine Cataract Cataract screening Cataract surgery IOL calculations Biometry Machine learning

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Risk factors and natural history of breast cancer in younger Chinese women

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World Journal of Clinical Oncology 2014年第5期5卷 1097-1106页

作者： Winnie Yeo Hang-Mei Lee Amy Chan Emily YY Chan Miranda CM Chan Keeng-Wai Chan Sharon WW Chan Foon-Yiu Cheung Polly SY Cheung Peter HK Choi Josette SY Chor William WL Foo Wing-Hong Kwan Stephen CK Law Lawrence PK Li Janice WH Tsang Yuk Tung Lorna LS wong ting-ting wong Chun-Chung Yau Tsz-Kok Yau Benny CY Zee Department of Clinical Oncology Chinese University of Hong Kong Prince of Wales Hospital Hong Kong Breast Cancer Foundation Jockey Club School of Public Health and Primary Care Chinese University of Hong Kong Department of Surgery Kwong Wah Hospital Diagnostix Pathology Laboratories Ltd Canossa Hospital Kowloon East Cluster Breast Centre Department of Surgery United Christian Hospital Department of Clinical Oncology Pamela Youde Nethersole Eastern Hospital Private Clinical Oncologist Radiotherapy and Oncology Centre Hong Kong Baptist Hospital Comprehensive Oncology Centre Hong Kong Sanatorium and Hospital Hong Kong Adventist Oncology Center Hong Kong Adventist Hospital Department of Clinical Oncology University of Hong Kong Department of Clinical Oncology Tuen Mun Hospital Private Surgeon Department of Clinical Oncology Princess Margaret Hospital

AIM: To investigate the age differences in the risk factors, clinicopathological characteristics and patterns of treatment of female breast cancer patients. METHODS: Seven thousand one hundred and fiftytwo women with primary breast cancer from the Hong Kong Breast Cancer Registry were recruited after receiving patients' consent, they were asked to complete standardized questionnaires which captured their sociodemographic characteristics and risk factors associated with breast cancer development. Among them, clinicopathological data and patterns of treatment were further collected from medical records of 5523 patients with invasive breast cancers. Patients were divided into two groups according to the age at diagnosis: younger(< 40 years old) vs older patients(≥ 40 years old) for subsequent analyses.RESULTS: Analysis on the sociodemographic characteristics and exposure to risk factors were performed on 7152 women with primary breast cancer and the results revealed that younger patients were more likely to have unhealthy lifestyles; these include a lack of exercise(85.4% vs 73.2%, P < 0.001), having high stress in life(46.1% vs 35.5%, P < 0.001), having dairy/meat-rich diets(20.2% vs 12.9%, P < 0.001),having alcohol drinking habit(7.7% vs 5.2%, P = 0.002). Younger patients were also more likely to have hormone-related risk factors including nulliparity(43.3% vs 17.8%, P < 0.001) and an early age at menarche(20.7% vs 13.2%, P < 0.001). Analyses on clinicopathological characteristics and patterns of treatment were performed on 5523 women diagnosed with invasive breast cancer. The invasive tumours in younger patients showed more aggressive pathological features such as having a higher percentage of grade 3 histology(45.7% vs 36.5%, P < 0.001), having a higher proportion of tumours with lymphovascular invasion(39.6% vs 33.2%, P = 0.003), and having multifocal disease(15.7% vs 10.3%, P < 0.001); they received different patterns of treatment than their older counterparts.CONCLUSION: Younger patients in Hong Kong are more

关键词： Hong Kong Breast Cancer Registry Breast cancer Younger Chinese women Sociodemographic characteristics Risk factors Clinicopathological characteristics Breast cancer treatment

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Immunoregulatory and Anti-cancer Activities of Combination Treatment of Novel Four-Herb Formula and Doxorubicin in 4T1-Breast Cancer Bearing Mice

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Chinese Journal of Integrative Medicine 2024年第4期30卷 311-321页

作者： Lea Ling-Yu Kan Ben Chung-Lap Chan Grace Gar-Lee Yue LI Pei-ting Sharon Sze-Man Hon HUANG Dan-qi Miranda Sin-Man Tsang Clara Bik-San Lau Ping-Chung Leung Chun-Kwok wong Institute of Chinese Medicine The Chinese University of Hong KongHong Kong SARChina State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants The Chinese University of Hong KongHong KongChina Department of Chemical Pathology The Chinese University of Hong KongHong Kong SARChina China-Australia International Research Centre for Chinese Medicine School of Health and Biomedical SciencesSTEM CollegeRMIT UniversityBundooraVictoriaAustralia Li Dak Sum Yip Yio Chin R&D Centre for Chinese Medicine The Chinese University of Hong Kong SARHong KongChina

Objective To investigate the in vivo immunomodulatory and anti-tumor mechanisms of the combined treatment of novel Four-Herb formula(4HF)and doxorubicin in triple-negative breast cancer(TNBC).Methods Murine-derived triple-negative mammary carcinoma cell line,4T1 cells,was cultured and inoculated into mouse mammary glands.Sixty-six mice were randomly assigned into 6 groups(n=11 in ench):naive,control,LD 4HF(low dose 4HF),HD 4HF(high dose 4HF),LD 4HF+D(low dose and doxorubicin),and D(doxorubicin).Apart from the naive group,each mouse received subcutaneous inoculation with 5×10^(5)4T1 cells resuspended in 100µL of normal saline in the mammary fat pads.Starting from the day of tumor cell inoculation,tumors were grown for 6 days.The LD and HD groups received daily oral gavage of 658 and 2,630 mg/kg 4HF,respectively.The LD 4HF+D group received daily oral gavage of 658 mg/kg 4HF and weekly intraperitoneal injection of doxorubicin(5 mg/kg).The D group received weekly intraperitoneal injections of doxorubicin(5 mg/kg).The treatment naive mice received daily oral gavage of 0.2 mL double distilled water and 0.1 mL normal saline via intraperitoneal injection once a week.The control group received daily oral gavage of 0.2 mL double-distilled water.The treatment period was 30 days.At the end of treatment,mice organs were harvested to analyze immunological activities via immunophenotyping,gene and multiplex analysis,histological staining,and gut microbiota analysis.Results Mice treated with the combination of 4HF and doxorubicin resulted in significantly reduced tumor and spleen burdens(Pting the anti-tumor immune response(P<

关键词： adjunctivetherapy breast cancer cytokines Chinese medicine tumor microenvironment

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The electroweak monopole–antimonopole pair in the standard model

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Communications in Theoretical Physics 2024年第3期76卷 113-119页

作者： Dan Zhu Khai-Ming wong Guo-Quan wong School of Physics Universiti Sains Malaysia11800 USMPenangMalaysia

We present the first numerical solution that corresponds to a pair of Cho–Maison monopoles and antimonopoles(MAPs) in the SU(2) × U(1) Weinberg–Salam(WS) theory.The monopoles are finitely separated,while each pole carries a magnetic charge ±4π/e.The positive pole is situated in the upper hemisphere,whereas the negative pole is in the lower hemisphere.The Cho–Maison MAP is investigated for a range of Weinberg angles,0.4675≤ tan θ_(W)≤10,and Higgs self-coupling,0 ≤ β ≤ 1.7704.The magnetic dipole moment(μm) and pole separation(d_(z)) of the numerical solutions are calculated and analyzed.The total energy of the system,however,is infinite due to point singularities at the locations of monopoles.

关键词： magnetic monopole Cho-Maison monopole Weinberg-Salam model

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Navigating reflux disease after achalasia treatments:Balancing risks and benefits

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World Journal of Gastroenterology 2024年第21期30卷 2740-2743页

作者： Ewen A Griffiths Enoch wong Department of Upper Gastrointestinal Surgery University Hospitals Birmingham NHS Foundation TrustBirmingham B152GWWest MidlandsUnited Kingdom Department of Immunology and Immunotherapy University of BirminghamBirmingham B152TTWest MidlandsUnited Kingdom

The peroral endoscopic myotomy(POEM)procedure has revolutionized the management of achalasia in many centres around the world as it offers patients a minimally invasive endoscopic solution to their dysphagia caused by achalasia.Alongside its success in alleviating dysphagia,concerns regarding postoperative gastroesophageal reflux disease have emerged as a pertinent issue which are not fully resolved.In this study,Nabi et al have comprehensively reviewed the topic of the prediction,prevention and management of gastroesophageal reflux after POEM.POEM is a purely endoscopic procedure which is usually performed without any anti-reflux procedure.Certain patients may be better served by a laparoscopic Heller’s myotomy and fundoplication and it is important that gastroenterologists and surgeons provide comprehensive risks and benefits of each achalasia treatment option so that patients can decide what treatment is best for them.This article by Nabi et al provides a comprehensive review of the current status of this issue to allow these discussions to occur.

关键词： Achalasia Gastro-esophageal reflux disease Laparoscopic heller’s myotomy Peroral endoscopic myotomy Fundoplication

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Options and survival benefits of conversion therapy for unresectable hepatocellular carcinoma

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World Journal of Gastroenterology 2024年第18期30卷 2479-2481页

作者： wong Hoi She Tan To Cheung Department of Surgery The University of Hong KongHong Kong 999077China

In the study by Wu et al,patients with unresectable hepatocellular carcinoma were subjected to transarterial chemoembolization(TACE)as a conversion therapy in order to render their tumors suitable for resection.A nomogram was devised and shown to be effective in predicting the survival of these patients.Generalization of the results,however,is questionable since the study subjects consisted of patients who had resection after TACE while excluding patients with the same disease but not suitable for TACE.Immunotherapy can be considered to be an option for conversion therapy.However,markers for determining responses to a conversion therapy and for guiding the decision between TACE and sequential immunotherapy have been lacking.The question of whether effective conversion therapy can truly enhance overall survival remains unanswered.

关键词： Conversion therapy Immunotherapy Liver resection Survival Transarterial chemoembolization Unresectable hepatocellular carcinoma

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Artificial intelligence analysis of videos to augment clinical assessment:an overview

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Neural Regeneration Research 2024年第4期19卷 717-718页

作者： David C.wong Stefan Williams University of Leeds Leeds Teaching Hospitals Trust LeedsUK

Observation is a fundamental part of the practice of clinical medicine.Observation of movement is particularly important for the neurologist.Conditions such as Parkinson’s disease,multiple sclerosis,stroke,epilepsy,and many others affect a person’s movement in characteristic ways.In some conditions,changes in the patient’s voice can be included in this-changes in sound caused by changes in the movements of speech.The clinician’s detection of a characteristic abnormality,and their judgment of its severity,plays a central role in both diagnosis and the assessment of prognosis or response to treatment.However,that practice depends upon a limited resource of experienced experts.In addition,these experts are limited by human visual judgment,which cannot reliably or precisely detect and measure small or subtle changes in movement(Williams et al.,2023).

关键词： clinical epilepsy diagnosis

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Synthetic brochosomes:Design,synthesis,and applications

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Nano Research 2024年第2期17卷 734-742页

作者： Lin Wang Jinsol Choi Tak-Sing wong Department of Mechanical Engineering The Pennsylvania State UniversityUniversity ParkPA 16802USA Materials Research Institute The Pennsylvania State UniversityUniversity ParkPA 16802USA Department of Biomedical Engineering The Pennsylvania State UniversityUniversity ParkPA 16802USA

Brochosomes,which are nanoscopic buckyball-shaped granules produced by leafhoppers,are one of the most intricate structures discovered in nature.Various functions of brochosomes have been proposed but only a few have been experimentally validated due to the challenge of fabricating their synthetic counterparts.Advancements in micro-and nanofabrication have recently led to the emergence of synthetic brochosomes,opening up new possibilities for innovative applications.This review explores the early discovery of natural brochosomes and their geometrical features,followed by the recent progress in fabricating synthetic brochosomes and their applications.Perspectives on future applications and challenges in the scalable manufacturing of synthetic brochosomes are discussed.

关键词： synthetic brochosomes leafhopper antireflection superhydrophobicity surface-enhanced Raman scattering photocatalyst energy harvesting

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Advances in Wireless,Batteryless,Implantable Electronics for Real‑Time,Continuous Physiological Monitoring

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Nano-Micro Letters 2024年第3期16卷 254-302页

作者： Hyeonseok Kim Bruno Rigo Gabriella wong Yoon Jae Lee Woon‑Hong Yeo IEN Center for Wearable Intelligent Systems and Healthcare Georgia Institute of TechnologyAtlantaGA 30332USA George W.Woodruff School of Mechanical Engineering Georgia Institute of TechnologyAtlantaGA 30332USA School of Electrical and Computer Engineering Georgia Institute of TechnologyAtlantaGA 30332USA Wallace H.Coulter Department of Biomedical Engineering Georgia Tech and Emory University School of MedicineAtlantaGA 30332USA Parker H.Petit Institute for Bioengineering and Biosciences Institute for MaterialsInstitute for Robotics and Intelligent MachinesGeorgia Institute of TechnologyAtlantaGA 30332USA

This review summarizes recent progress in developing wireless,batteryless,fully implantable biomedical devices for real-time continuous physiological signal monitoring,focusing on advancing human health care.Design considerations,such as biological constraints,energy sourcing,and wireless communication,are discussed in achieving the desired performance of the devices and enhanced interface with human tissues.In addition,we review the recent achievements in materials used for developing implantable systems,emphasizing their importance in achieving multi-functionalities,biocompatibility,and hemocompatibility.The wireless,batteryless devices offer minimally invasive device insertion to the body,enabling portable health monitoring and advanced disease diagnosis.Lastly,we summarize the most recent practical applications of advanced implantable devices for human health care,highlighting their potential for immediate commercialization and clinical uses.

关键词： Implantable electronics Biomedical systems Batteryless devices Wireless electronics Physiological signal monitoring

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