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Intra-articular sustained-release of pirfenidone as a disease-modifying treatment for early osteoarthritis

Bioactive Materials 2024年第9期39卷 255-272页

作者： Xiaobo Zhu Mingde Cao Kejia Li Yau-Tsz Chan Hon-Fai Chan yi-wah mak Hao Yao Jing Sun Michael Tim-Yun Ong Kevin Ki-Wai Ho Chien-Wei Lee Oscar Kuang-Sheng Lee Patrick Shu-Hang Yung Yangzi Jiang Institute for Tissue Engineering and Regenerative Medicine School of Biomedical SciencesFaculty of MedicineThe Chinese University of Hong KongShatinHong Kong Special Administrative Region of ChinaChina School of Biomedical Sciences Faculty of MedicineThe Chinese University of Hong KongShatinHong Kong Special Administrative Region of Chin1China Department of Orthopaedics&Traumatology Faculty of MedicineThe Chinese University of Hong KongPrince of Wales HospitalShatinHong Kong Special Administrative Region of Chin1China Center for Neuromusculoskeletal Restorative Medicine Hong Kong Special Administrative Region of Chin1China Key Laboratory for Regenerative Medicine Ministry of EducationSchool of Biomedical SciencesFaculty of MedicineThe Chinese University of Hong KongHong Kong Special Administrative Region of Chin1China Department of Orthopaedic Surgery The First Affiliated HospitalSchool of MedicineZhejiang UniversityChina

Osteoarthritis(OA)is a major clinical challenge,and effective disease-modifying drugs for OA are still lacking due to the complicated pathology and scattered treatment *** early treatments are urgently needed to prevent OA *** excessive amount of transforming growth factorβ(TGFβ)is one of the major causes of synovial fibrosis and subchondral bone sclerosis,and such pathogenic changes in early OA precede cartilage *** we report a novel strategy of intra-articular sustained-release of pirfenidone(PFD),a clinically-approved TGFβinhibitor,to achieve disease-modifying effects on early OA *** found that PFD effectively restored the mineralization in the presence of excessive amount of TGFβ1(as those levels found in patients’synovial fluid).A monthly injection strategy was then designed of using poly lactic-co-glycolic acid(PLGA)microparticles and hyaluronic acid(HA)solution to enable a sustained release of PFD(the“PLGA-PFD+HA”strategy).This strategy effectively regulated OA progression in destabilization of the medial meniscus(DMM)-induced OA mice model,including preventing subchondral bone loss in early OA and subchondral bone sclerosis in late OA,and reduced synovitis and pain with cartilage preservation *** finding suggests the promising clinical application of PFD as a novel disease-modifying OA drug.

关键词： TGFβ1 signaling Osteoarthritis Subchondral bone Pirfenidone DMOAD

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CD137L,a driver of harmful inflammation in the nervous system

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Neural Regeneration Research 2023年第11期18卷 2387-2388页

作者： Hiu yi Wong Amanda C.Y.Chan Anselm mak Herbert Schwarz Division of Life Science State Key Laboratory of Molecular NeuroscienceMolecular Neuroscience CenterThe Hong Kong University of Science and TechnologyHong Kong Special Administrative RegionChina Hong Kong Center for Neurodegenerative Diseases Hong Kong Special Administrative RegionChina Division of Neurology University Medicine ClusterNational University HospitalSingapore Department of Medicine Yong Loo Lin School of MedicineNational University of SingaporeSingapore Division of Rheumatology University Medicine ClusterNational University Health SystemDepartment of MedicineYong Loo Lin School of MedicineNational Univesity of SingaporeSingapore Department of Physiology and Immunology ProgrammeYong Loo Lin School of MedicineNational University of SingaporeSingapore Integrative Sciences and Engineering Programme NUS Graduate SchoolNational University of SingaporeSingapore

CD137 (TNFRSF9,4-1BB) is a member of the tumor necrosis factor (TNF) receptor family and a potent costimulatory *** levels of CD137 are expressed on T cells upon ***137 signaling in T cells,either by cognate interaction with antigen-presenting cells (APC)or by agonistic anti-CD137 antibodies,strongly enhances proliferation,interferon-y secretion,and cytolytic activity of T ***,CD137 signaling is a main driver of cellular,type 1 helper T cells (Th1)and type 1 cytolytic T cells (Tc1) polarised immune responses.

关键词： CD137 CD137L inflammation

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Relationship between hepatitis C virus infection and type 2 diabetes mellitus:Meta-analysis

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World Journal of Gastroenterology 2012年第14期18卷 1642-1651页

作者： Cho Naing Joon wah mak Syed Imran Ahmed Mala Maung Faculty of Medicine and Health International Medical UniversityKuala Lumpur 57000Malaysia

AIM:To investigate the association between hepatitis C infection and type 2 diabetes ***:Observational studies assessing the relationship between hepatitis C infection and type 2 diabetes mellitus were identified via electronic and hand *** published between 1988 to March 2011 were screened,according to the inclusion criteria set for the present *** performed separate analyses for the comparisons between hepatitis C virus(HCV) infected and not infected,and HCV infected and hepatitis B virus *** included studies were further subgrouped according to the study *** was assessed using I2 *** summary odds ratios with their corresponding 95% CIs were calculated based on a random-effects *** included studies were subgrouped according to the study *** assess any factor that could potentially affect the outcome,results were further stratified by age group(proportion of ≥ 40 years),gender(proportion of male gender),body mass index(BMI)(pro-portion of BMI ≥ 27),and family history of diabetes(i.e.,self reported).For stability of results,a sensitivity analysis was conducted including only prospective ***:Combining the electronic database and hand searches,a total of 35 observational studies(in 31 articles) were identified for the final *** on random-effects model,17 studies(n = 286 084) compared hepatitis C-infected patients with those who were uninfected [summary odds ratio(OR):1.68,95% CI:1.15-2.45].Of these 17 studies,7 were both a cross-sectional design(41.2%) and cohort design(41.2%),while 3 were case-control studies(17.6%).Nineteen studies(n = 51 156) compared hepatitis C-infected participants with hepatitis B-infected(summary OR:1.92,95% CI:1.41-2.62).Of these 19 studies,4(21.1%),6(31.6%) and 9(47.4%) were cross-sectional,cohort and case-control studies,respectively.A sensitivity analysis with 3 prospective studies indicated that hepatitis C-infected patients had a

关键词： Hepatitis C Type 2 diabetes mellitus Observational studies Meta-analysis

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Microwave heating as a universal method to transform confined molecules into armchair graphene nanoribbons

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Nano Research 2023年第7期16卷 10644-10651页

作者： Haoyuan Zhang yingzhi Chen Kunpeng Tang Ziheng Lin Xuan Li Hongwei Zhang yifan Zhang Chi Ho Wong Chi wah Leung Chee Leung mak Yuan Hu Weili Cui Kecheng Cao Lei Shi State Key Laboratory of Optoelectronic Materials and Technologies Nanotechnology Research CenterGuangdong Province Key Lab of Display Material and TechnologySchool of Materials Science and EngineeringSun Yat-sen UniversityGuangzhou 510275China Huzhou Key Laboratory of Environmental Functional Materials and Pollution Control School of EngineeringHuzhou UniversityHuzhou 313000China Department of Industrial and Systems Engineering Research Institute for Advanced ManufacturingThe Hong Kong Polytechnic UniversityHong Kong 999077China Department of Applied Physics The Hong Kong Polytechnic UniversityHong Kong 999077China Shanghai Key Laboratory of High-resolution Electron Microscopy ShanghaiTech UniversityShanghai 201210China

Armchair graphene nanoribbons(AGNRs)with sub-nanometer width are potential materials for the fabrication of novel nanodevices thanks to their moderate direct band *** are usually synthesized by polymerizing precursor molecules on substrate ***,it is time-consuming and not suitable for large-scale *** can also be grown by transforming precursor molecules inside single-walled carbon nanotubes(SWCNTs)via furnace annealing,but the obtained AGNRs are normally *** this work,microwave heating is applied for transforming precursor molecules into *** fast heating process allows synthesizing the AGNRs in *** different molecules were successfully transformed into AGNRs,suggesting that it is a universal *** importantly,as demonstrated by Raman spectroscopy,aberrationcorrected high-resolution transmission electron microscopy and theoretical calculations,less twisted AGNRs are synthesized by the microwave heating than the furnace *** results reveal a route for rapid production of AGNRs in large scale,which would benefit future applications in novel AGNRs-based semiconductor devices.

关键词： armchair graphene nanoribbons(AGNRs) microwave heating single-walled carbon nanotubes(SWCNTs) Raman spectroscopy

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On the Integrability of the Abel and of the Extended Liénard Equations

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Acta Mathematicae Applicatae Sinica 2019年第4期35卷 722-736页

作者： Man Kwong mak Tiberiu HARKO Departamento de Fsica Facultad de Ciencias Naturales Universidad de Atacama Copayapu 485 Copiapo Chile Department of Physics Babes-Bolyai University Kogalniceanu Street Cluj-Napoca 400084 Romania School of Physics Sun Yat-Sen University Guangzhou 510275 China

We present some exact integrability cases of the extended Liénard equation y′′+ f(y)(y′)n +k(y)(y′)m + g(y)y′+ h(y) = 0, with n > 0 and m > 0 arbitrary constants, while f(y), k(y), g(y), and h(y) are arbitrary functions. The solutions are obtained by transforming the equation Liénard equation to an equivalent first kind first order Abel type equation given bydv/dy= f(y)v3-n+ k(y)v3-m+ g(y)v2+ h(y)v3, with v = 1/y′.As a first step in our study we obtain three integrability cases of the extended quadratic-cubic Liénard equation,corresponding to n = 2 and m = 3, by assuming that particular solutions of the associated Abel equation are known. Under this assumption the general solutions of the Abel and Liénard equations with coefficients satisfying some differential conditions can be obtained in an exact closed form. With the use of the Chiellini integrability condition, we show that if a particular solution of the Abel equation is known, the general solution of the extended quadratic cubic Liénard equation can be obtained by quadratures. The Chiellini integrability condition is extended to generalized Abel equations with g(y) ≡ 0 and h(y) ≡ 0, and arbitrary n and m, thus allowing to obtain the general solution of the corresponding Liénard equation. The application of the generalized Chiellini condition to the case of the reduced Riccati equation is also considered.

关键词： Abel equation Liénard equation general solutions integrability conditions

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Epidemiology and natural history of Wilson's disease in the Chinese: A territory-based study in Hong Kong between 2000 and 2016

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World Journal of Gastroenterology 2017年第43期23卷 7716-7726页

作者： Ka-Shing Cheung Wai-Kay Seto James Fung Lung-yi mak Ching-Lung Lai Man-Fung Yuen Department of Medicine The University of Hong KongQueen Mary Hospital State Key Laboratory for Liver Research The University of Hong Kong

AIM To investigate the epidemiology and natural history of Wilson's disease in the *** Data were retrieved via electronic search of hospital medical registry of the Hong Kong Hospital Authority,which covers all the public healthcare services. We identified cases of Wilson's disease between 2000 and 2016 by the International Classification of Diseases(ICD)-9 code. We analyzed the incidence rate,prevalence and adverse outcomes of Wilson's *** We identified 211 patients(male cases 104; female cases 107; median age 27.2 years,IQR: 17.1-38.6 years; duration of follow-up 8.0 years,IQR: 5.0-14.0 years). The average annual incidence rate was 1.44 per million person-years while the prevalence was 17.93 per million. Between 2000 and 2016,there was a decrease in the annual incidence rate from 1.65 to 1.23 per million person-years(P = 0.010),whereas there was an increase in the annual prevalence from 7.80 to 25.20 per million(P < 0.001). Among the 176 cases with hepatic involvement,38(21.6%) had cirrhosis,three(1.7%) developed hepatocellular carcinoma,24(13.6%) underwent liver transplantations,and 26(14.8%) died. Seven patients had concomitant chronic viral hepatitis B or C. The 5-year and 10-years rates of overall survival were 92.6% and 89.5%,and for transplant-free survival rates 91.8% and 87.4%,respectively. Cirrhosis and possibly chronic viral hepatitis were associated with poorer overall survival. CONCLUSION There was a significant increase in the prevalence of Wilson's disease in Hong Kong. The prognosis was favorable except for those with cirrhosis or concomitant viral hepatitis.

关键词： Hepaticolenticular degeneration Cirrhosis Hepatocellular carcinoma Transplantation

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Prediction of hepatocellular carcinoma development by aminotransferase to platelet ratio index in primary biliary cholangitis

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World Journal of Gastroenterology 2017年第44期23卷 7863-7874页

作者： Ka-Shing Cheung Wai-Kay Seto James Fung Lung-yi mak Ching-Lung Lai Man-Fung Yuen Department of Medicine The University of Hong Kong Queen Mary Hospital State Key Laboratory for Liver Research The University of Hong Kong

AIM To investigate the usefulness of aspartate aminotransferase to platelet ratio index(APRI) in predicting hepatocellular carcinoma(HCC) risk in primary biliary cholangitis(PBC).METHODS We identified PBC patients between 2000 and 2015 by searching the electronic medical database of a tertiary center. The hazard ratio(HR) of HCC with different risk factors was determined by Cox proportional hazards model. RESULTS One hundred and forty-four PBC patients were recru-ited. Patients were diagnosed at a median age of 57.8 years [interquartile range(IQR): 48.7-71.5 years), and 41(28.5%) patients had cirrhosis at baseline. The median follow-up duration was 6.9 years(range: 1.0-26.3 years). Twelve patients developed HCC, with an incidence rate of 10.6 cases per 1000 patient-years. The overall 5-, 10-and 15-year cumulative incidences of HCC were 2.3% 95%CI: 0%-4.8%), 8.4%(95%CI: 1.8%-14.5%) and 21.6%(6.8%-34.1%), respectively. Older age(HR = 1.07), cirrhosis(HR = 4.38) and APRI at 1 year after treatment(APRI-r1) > 0.54(HR = 3.94) were independent factors for HCC development. APRI-r1, when combined with treatment response, further stratified HCC risk(log rank P < 0.05). The area under receiver operating curve of APRI-r1 in predicting HCC was 0.77(95%CI: 0.64-0.88).CONCLUSION APRI-r1 can be used to predict the development of HCC in PBC patients. Combination of APRI-r1 with treatment response can further stratify the HCC risk.

关键词： Aspartate aminotransferase Platelet ratio index Hepatocellular carcinoma Primary biliary cholangitis Ursodeoxycholic acid Cirrhosis

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Orthopedic surgery and its complication in systemic lupus erythematosus

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World Journal of Orthopedics 2014年第1期5卷 38-44页

作者： Anselm mak Division of Rheumatology Department of Medicine University Medicine Cluster Department of Medicine Yong Loo Lin School of Medicine National University of Singapore

Systemic lupus erythematosus(SLE) is a multi-systemic immune-complex mediated autoimmune condition which chiefly affects women during their prime year. While the management of the condition falls into the specialty of internal medicine, patients with SLE often present with signs and symptoms pertaining to the territory of orthopedic surgery such as tendon rupture, carpal tunnel syndrome, osteonecrosis, osteoporotic fracture and infection including septic arthritis, osteomyelitis and spondylodiscitis. While these orthopedicrelated conditions are often debilitating in patients with SLE which necessitate management by orthopedic specialists, a high index of suspicion is necessary in diagnosing these conditions early because lupus patients with potentially severe orthopedic conditions such as osteomyelitis frequently present with mild symptoms and subtle signs such as low grade fever, mild hip pain and back tenderness. Additionally, even if these orthopedic conditions can be recognized, complications as a result of surgical procedures are indeed not uncommon. SLE per se and its various associated pharmacological treatments may pose lupus patients to certain surgical risks if they are not properly attended to andmanaged prior to, during and after surgery. Concerted effort of management and effective communication among orthopedic specialists and rheumatologists play an integral part in enhancing favorable outcome and reduction in postoperative complications for patients with SLE through thorough pre-operative evaluation, careful peri-operative monitoring and treatment, as well as judicious postoperative care.

关键词： orthopedics Complications Surgery Systemic lupus erythematosus Operation

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An Exact Anisotropic Quark Star Model

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Chinese Journal of Astronomy and Astrophysics 2002年第3期2卷 248-259页

作者： M.K.mak T.Harko DepartmentofPhysics TheHongKongUniversityofScienceandTechnologyClearWaterBayHongKong DepartmentofPhysics TheUniversityofHongKongPokfulamHongKong

We present an exact analytical solution of the gravitational field equations describing a static spherically symmetric anisotropic quark matter distribution. The radial pressure inside the star is assumed to obey a linear equation of state, while the tangential pressure is a complicated function of the radial coordinate. In order to obtain the general solution of the field equations a particular density profile inside the star is also assumed. The anisotropic pressure distribution leads to an increase in the maximum radius and mass of the quark star, which in the present model is around three solar masses.

关键词： Stars - quark: interior solution: anisotropy

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A digital microfluidic system with 3D microstructures for single-cell culture

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Microsystems & Nanoengineering 2020年第1期6卷 1296-1305页

作者： Jiao Zhai Haoran Li Ada Hang-Heng Wong Cheng Dong Shuhong yi Yanwei Jia Pui-In mak Chu-Xia Deng Rui PMartins State-Key Laboratory of Analog and Mixed-Signal VLSI Institute of MicroelectronicsUniversity of MacaoMacao SARChina Faculty of Science and Technology-ECE University of MacaoMacao SARChina Cancer Center Faculty of Health SciencesUniversity of MacaoMacao SARChina Liver Transplantation Center the Third Affiliated HospitalSun Yat-sen University510000 GuangzhouChina on leave from Instituto Superior Técnico Universidade de LisboaLisboaPortugal

Despite the precise controllability of droplet samples in digital microfluidic(DMF)systems,their capability in isolating single cells for long-time culture is still limited:typically,only a few cells can be captured on an *** fabricating small-sized hydrophilic micropatches on an electrode aids single-cell capture,the actuation voltage for droplet transportation has to be significantly raised,resulting in a shorter lifetime for the DMF chip and a larger risk of damaging the *** this work,a DMF system with 3D microstructures engineered on-chip is proposed to form semi-closed micro-wells for efficient single-cell isolation and long-time *** optimum results showed that approximately 20%of the micro-wells over a 30×30 array were occupied by isolated single *** addition,low-evaporation-temperature oil and surfactant aided the system in achieving a low droplet actuation voltage of 36V,which was 4 times lower than the typical 150 V,minimizing the potential damage to the cells in the droplets and to the DMF *** exemplify the technological advances,drug sensitivity tests were run in our DMF system to investigate the cell response of breast cancer cells(MDA-MB-231)and breast normal cells(MCF-10A)to a widely used chemotherapeutic drug,Cisplatin(Cis).The results on-chip were consistent with those screened in conventional 96-well *** novel,simple and robust single-cell trapping method has great potential in biological research at the single cell level.

关键词： culture system sized

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