Corneal neuromas,also termed microneuromas,refer to microscopic,irregula rly-shaped enlargements of terminal subbasal nerve endings at sites of nerve damage or injury.The formation of corneal neuromas results from dam...Corneal neuromas,also termed microneuromas,refer to microscopic,irregula rly-shaped enlargements of terminal subbasal nerve endings at sites of nerve damage or injury.The formation of corneal neuromas results from damage to corneal nerves,such as following corneal pathology or corneal or intraocular surge ries.Initially,denervated areas of sensory nerve fibers become invaded by sprouts of intact sensory nerve fibers,and later injured axons regenerate and new sprouts called neuromas develop.In recent years,analysis of corneal nerve abnormalities including corneal neuromas which can be identified using in vivo confocal microscopy,a non-invasive imaging technique with microscopic resolution,has been used to evaluate corneal neuropathy and ocular surface dysfunction.Corneal neuromas have been shown to be associated with clinical symptoms of discomfort and dryness of eyes,and are a promising surrogate biomarker for ocular surface diseases,such as neuropathic corneal pain,dry eye disease,diabetic corneal neuropathy,neurotrophic keratopathy,Sjogren's syndrome,bullous keratopathy,post-refra ctive surgery,and others.In this review,we have summarized the current literature on the association between these ocular surface diseases and the presentation of corneal microneuromas,as well as elaborated on their pathogenesis,visualization via in vivo confocal microscopy,and utility in monitoring treatment efficacy.As current quantitative analysis on neuromas mainly relies on manual annotation and quantification,which is user-dependent and labor-intensive,future direction includes the development of artificial intelligence software to identify and quantify these potential imaging biomarkers in a more automated and sensitive manner,allowing it to be applied in clinical settings more efficiently.Combining imaging and molecular biomarkers may also help elucidate the associations between corneal neuromas and ocular surface diseases.展开更多
Diabetic corneal neuropathy and diabetic retinopathy are ocular complications occurring in the context of diabetes mellitus.Diabetic corneal neuropathy refers to the progressive damage of corneal nerves.Diabetic retin...Diabetic corneal neuropathy and diabetic retinopathy are ocular complications occurring in the context of diabetes mellitus.Diabetic corneal neuropathy refers to the progressive damage of corneal nerves.Diabetic retinopathy has traditionally been considered as damage to the retinal microvasculature.However,growing evidence suggests that diabetic retinopathy is a complex neurovascular disorder resulting from dysfunction of the neurovascular unit,which includes both the retinal vascular structures and neural tissues.Diabetic retinopathy is one of the leading causes of blindness and is frequently screened for as part of diabetic ocular screening.However,diabetic corneal neuropathy is commonly overlooked and underdiagnosed,leading to severe ocular surface impairment.Several studies have found that these two conditions tend to occur together,and they share similarities in their pathogenesis pathways,being triggered by a status of chronic hyperglycemia.This review aims to discuss the interconnection between diabetic corneal neuropathy and diabetic retinopathy,whether diabetic corneal neuropathy precedes diabetic retinopathy,as well as the relation between the stage of diabetic retinopathy and the severity of corneal neuropathy.We also endeavor to explore the relevance of a corneal screening in diabetic eyes and the possibility of using corneal nerve measurements to monitor the progression of diabetic retinopathy.展开更多
Laser refractive surgery is one of the most commonly performed procedures worldwide.In laser refractive surgery,Femtosecond Laser in Situ Keratomileusis and Refractive Lenticule Extraction have emerged as promising al...Laser refractive surgery is one of the most commonly performed procedures worldwide.In laser refractive surgery,Femtosecond Laser in Situ Keratomileusis and Refractive Lenticule Extraction have emerged as promising alternatives to microkeratome Laser in Situ Keratomileusis and Photorefractive Keratectomy.Following laser refractive surgery,the corneal nerves,epithelial and stromal cells release neuromediators,including neurotrophins,neuropeptides and neurotransmitters.Notably,nerve growth factor,substance P,calcitonin gene-related peptide and various cytokines are important mediators of neurogenic inflammation and corneal nerve regeneration.Alterations in neuromediator profiles and ocular surface parameters following laser refractive surgery are attributed to the surgical techniques and the severity of tissue insult induced.In this review,we will discuss the(1)Functions of neuromediators and their physiological and clinical significance;(2)Changes in the neuromediators following various laser refractive surgeries;(3)Correlation between neuromediators,ocular surface health and corneal nerve status;and(4)Future directions,including the use of neuromediators as potential biomarkers for ocular surface health following laser refractive surgery,and as adjuncts to aid in corneal regeneration after laser refractive surgery.展开更多
Diabetic neuropathy is a prevalent microvascular complication of diabetes mellitus,affecting nerves in all parts of the body including corneal nerves and peripheral nervous system,leading to diabetic corneal neuropath...Diabetic neuropathy is a prevalent microvascular complication of diabetes mellitus,affecting nerves in all parts of the body including corneal nerves and peripheral nervous system,leading to diabetic corneal neuropathy and diabetic peripheral neuropathy,respectively.Diabetic peripheral neuropathy is diagnosed in clinical practice using electrophysiological nerve conduction studies,clinical scoring,and skin biopsies.However,these diagnostic methods have limited sensitivity in detecting small-fiber disease,hence they do not accurately reflect the status of diabetic neuropathy.More recently,analysis of alterations in the corneal nerves has emerged as a promising surrogate marker for diabetic peripheral neuropathy.In this review,we will discuss the relationship between diabetic corneal neuropathy and diabetic peripheral neuropathy,elaborating on the foundational aspects of each:pathogenesis,clinical presentation,evaluation,and management.We will further discuss the relevance of diabetic corneal neuropathy in detecting the presence of diabetic peripheral neuropathy,particularly early diabetic peripheral neuropathy;the correlation between the severity of diabetic corneal neuropathy and that of diabetic peripheral neuropathy;and the role of diabetic corneal neuropathy in the stratification of complications of diabetic peripheral neuropathy.展开更多
The detection of Epstein-Barr virus(EBV)in nasopharyngeal carcinoma(NPC)has evolved over the last40 years,transitioning from simple serological tests of latent viral infection to extremely sensitive measurements of
Small Aδand C nerve fibers of the sensory and autonomic nervous systems constitute 70–90%of peripheral nerve fibers including corneal nerves(Muller et al.,2003).Corneal nerves originate from the ophthalmic branch of...Small Aδand C nerve fibers of the sensory and autonomic nervous systems constitute 70–90%of peripheral nerve fibers including corneal nerves(Muller et al.,2003).Corneal nerves originate from the ophthalmic branch of the trigeminal nerve and enter the cornea at the limbus radially from all directions toward the central cornea at the level of anterior and middle stroma.The subepithelial nerve plexus lies at the interface between the Bowman layer and anterior stroma.They then divide into smaller branches and turn 90°toward Bowman’s layer(Muller et al.,2003),travelling between Bowman’s layer and the basal epithelial layer and forming the sub-basal nerve plexus(Muller et al.,2003).展开更多
BACKGROUND The development of new vasculatures(angiogenesis)is indispensable in supplying oxygen and nutrients to fuel tumor growth.Epigenetic dysregulation in the tumor vasculature is critical to colorectal cancer(CR...BACKGROUND The development of new vasculatures(angiogenesis)is indispensable in supplying oxygen and nutrients to fuel tumor growth.Epigenetic dysregulation in the tumor vasculature is critical to colorectal cancer(CRC)progression.Sirtuin(SIRT)enzymes are highly expressed in blood vessels.BZD9L1 benzimidazole analogue is a SIRT 1 and 2 inhibitor with reported anticancer activities in CRC.However,its role has yet to be explored in CRC tumor angiogenesis.AIM To investigate the anti-angiogenic potential of BZD9L1 on endothelial cells(EC)in vitro,ex vivo and in HCT116 CRC xenograft in vivo models.METHODS EA.hy926 EC were treated with half inhibitory concentration(IC50)(2.5μM),IC50(5.0μM),and double IC50(10.0μM)of BZD9L1 and assessed for cell proliferation,adhesion and SIRT 1 and 2 protein expression.Next,2.5μM and 5.0μM of BZD9L1 were employed in downstream in vitro assays,including cell cycle,cell death and sprouting in EC.The effect of BZD9L1 on cell adhesion molecules and SIRT 1 and 2 were assessed via real-time quantitative polymerase chain reaction(qPCR).The growth factors secreted by EC post-treatment were evaluated using the Quantibody Human Angiogenesis Array.Indirect co-culture with HCT116 CRC cells was performed to investigate the impact of growth factors modulated by BZD9L1-treated EC on CRC.The effect of BZD9L1 on sprouting impediment and vessel regression was determined using mouse choroids.HCT116 cells were also injected subcutaneously into nude mice and analyzed for the outcome of BZD9L1 on tumor necrosis,Ki67 protein expression indicative of proliferation,cluster of differentiation 31(CD31)and CD34 EC markers,and SIRT 1 and 2 genes via hematoxylin and eosin,immunohistochemistry and qPCR,respectively.RESULTS BZD9L1 impeded EC proliferation,adhesion,and spheroid sprouting through the downregulation of intercellular adhesion molecule 1,vascular endothelial cadherin,integrin-alpha V,SIRT1 and SIRT2 genes.The compound also arrested the cells at G1 phase and induced apoptosis in the EC.In mouse choroids,BZD9L1 inhibited sprouting and regressed sprouting vessels compared to the negative control.Compared to the negative control,the compound also reduced the protein levels of angiogenin,basic fibroblast growth factor,platelet-derived growth factor and placental growth factor,which then inhibited HCT116 CRC spheroid invasion in co-culture.In addition,a significant reduction in CRC tumor growth was noted alongside the downregulation of human SIRT1(hSIRT1),hSIRT2,CD31,and CD34 EC markers and murine SIRT2 gene,while the murine SIRT1 gene remained unaffected,compared to vehicle control.Histology analyses revealed that BZD9L1 at low(50 mg/kg)and high(250 mg/kg)doses reduced Ki-67 protein expression,while BZD9L1 at the high dose diminished tumor necrosis compared to vehicle control.CONCLUSION These results highlighted the anti-angiogenic potential of BZD9L1 to reduce CRC tumor progression.Furthermore,together with previous anticancer findings,this study provides valuable insights into the potential of BZD9L1 to co-target CRC tumor vasculatures and cancer cells via SIRT1 and/or SIRT2 down-regulation to improve the therapeutic outcome.展开更多
BACKGROUND Hepatitis C virus(HCV)is a leading cause of liver cirrhosis and hepatocellular carcinoma globally.Sofosbuvir/velpatasvir(SOF/VEL)is an effective pangenotypic direct-acting antiviral combination for treatmen...BACKGROUND Hepatitis C virus(HCV)is a leading cause of liver cirrhosis and hepatocellular carcinoma globally.Sofosbuvir/velpatasvir(SOF/VEL)is an effective pangenotypic direct-acting antiviral combination for treatment of chronic HCV infection.While the addition of ribavirin(RBV)to SOF/VEL improved sustained virological response(SVR12)in genotype 3(GT3)decompensated cirrhosis patients,the benefits of RBV in GT3 compensated cirrhosis patients receiving SOF/VEL remains unclear.AIM To evaluate the efficacy and safety of SOF/VEL,with or without RBV in GT3 compensated cirrhosis patients.METHODS We searched four electronic databases(PubMed/Medline,Embase,Cochrane Library and Web of Science)from inception up to June 2021 using both free text and MeSH terms.There was no restriction on language,geography,publication dates and publication status(full text or abstracts).All GT3 compensated cirrhosis patients treated with 12 wk of SOF/VEL,with or without RBV,were included,regardless of age,gender or prior treatment experience.The primary outcome was sustained virological response 12-wk posttreatment(SVR12).The secondary outcome was treatment-related adverse events,as defined by symptomatic anemia requiring transfusion or a drop in hemoglobin beyond 2 g/dL.The pooled relative risk(RR),95%CI and heterogeneity(I^(2))were estimated using Review Manager version 5.3.RESULTS From 1752 citations,a total of seven studies(2 randomized controlled trials,5 cohort studies)with 1088 subjects were identified.The SVR12 was similar in GT3 compensated cirrhosis patients,regardless of the use of RBV,for both the intention-to-treat RR 1.03,95%CI:0.99-1.07;I^(2)=0%)and the per-protocol analysis(RR:1.03,95%CI:0.99-1.07;I^(2)=48%).The overall pooled rate of treatment-related adverse events was 7.2%.Addition of RBV increased the pooled risk of treatment-related adverse events in GT3 compensated cirrhosis patients receiving SOF/VEL(RR:4.20,95%CI:1.29-13.68;I^(2)=0%).Subgroup analysis showed that RBV was associated with a higher SVR12 in GT3 compensated cirrhosis patients with baseline resistance-associated substitutions.However,addition of RBV did not significantly increase the SVR12 among treatment-experienced GT3 compensated cirrhosis patients.CONCLUSION Ribavirin was not associated with higher SVR12 in GT3 compensated cirrhosis patients receiving SOF/VEL.Our findings suggest a limited role for RBV as routine add-on therapy to SOF/VEL in GT3 compensated cirrhosis patients.展开更多
Submacular haemorrhage(SMH)is a sight threatening complication that can occur in exudative age related macular degeneration(AMD),but has been described to occur more frequently in eyes with polypoidal choroidal vascul...Submacular haemorrhage(SMH)is a sight threatening complication that can occur in exudative age related macular degeneration(AMD),but has been described to occur more frequently in eyes with polypoidal choroidal vasculopathy(PCV).Left untreated,SMH carries a grave visual prognosis.Thus,expedient diagnosis and effective management of this complication is of paramount importance.The treatment strategies for SMH include(I)displacement of blood from the fovea,usually by injection of an expansile gas;(II)pharmacologic clot lysis such as with recombinant tissue plasminogen activator(rtPA);and(III)treatment of the underlying choroidal neovascularization(CNV)or PCV,such as with anti-vascular endothelial growth factor(anti-VEGF)agents.These three strategies have been employed in isolation or in combination,some concurrently and others in stages.rtPA has demonstrable effect on the liquefaction of submacular clots but there are remaining uncertainties with regards to the dose,safety and the timing of initial and repeat treatments.Potential side effects of rtPA include retinal pigment epithelial toxicity,increased risk of breakthrough vitreous haemorrhage and systemic toxicity.In cases presenting early,pneumatic displacement alone with anti-VEGF may be sufficient.Anti-VEGF monotherapy is a viable treatment option particularly in patients with thinner SMH and those who are unable to posture post pneumatic displacement.展开更多
Retinal angiogenic diseases,such as diabetic retinopathy(DR)and age-related macular degeneration(AMD)represent the leading causes of vision impairment in developed countries.There is strong evidence that dysregulated ...Retinal angiogenic diseases,such as diabetic retinopathy(DR)and age-related macular degeneration(AMD)represent the leading causes of vision impairment in developed countries.There is strong evidence that dysregulated metabolic pathways contribute to DR as known risk factors do not explain all cases and the phenomenon of metabolic memory persists for decades or longer.Some early studies also showed that changes of plasma metabolic profiles are associated with AMD.Metabolic abnormalities can be explored using the techniques of the new science of metabolomics.In this presentation,several metabolomics workflows as well as the application of data independent acquisition mass spectrometry(DIA-MS)in metabolomics will be discussed.Our recent findings from metabolomics studies on DR and AMD will be presented.展开更多
Diabetes poses a considerable global health challenge,with varying levels of diabetes knowledge among healthcare professionals,highlighting the importance of diabetes training.Large Language Models(LLMs)provide new in...Diabetes poses a considerable global health challenge,with varying levels of diabetes knowledge among healthcare professionals,highlighting the importance of diabetes training.Large Language Models(LLMs)provide new insights into diabetes training,but their performance in diabetes-related queries remains uncertain,especially outside the English language like Chinese.We first evaluated the performance of ten LLMs:ChatGPT-3.5,ChatGPT-4.0,Google Bard,LlaMA-7B,LlaMA2-7B,Baidu ERNIE Bot,Ali Tongyi Qianwen,MedGPT,HuatuoGPT,and Chinese LlaMA2-7B on diabetes-related queries,based on the Chinese National Certificate Examination for Primary Diabetes Care in China(NCE-CPDC)and the English Specialty Certificate Examination in Endocrinology and Diabetes of Membership of the Royal College of Physicians of the United Kingdom.Second,we assessed the training of primary care physicians(PCPs)without and with the assistance of ChatGPT-4.0 in the NCE-CPDC examination to ascertain the reliability of LLMs as medical assistants.We found that ChatGPT-4.0 outperformed other LLMs in the English examination,achieving a passing accuracy of 62.50%,which was significantly higher than that of Google Bard,LlaMA-7B,and LlaMA2-7B.For the NCE-CPFC examination,ChatGPT-4.0,Ali Tongyi Qianwen,Baidu ERNIE Bot,Google Bard,MedGPT,and ChatGPT-3.5 successfully passed,whereas LlaMA2-7B,HuatuoGPT,Chinese LLaMA2-7B,and LlaMA-7B failed.ChatGPT-4.0(84.82%)surpassed all PCPs and assisted most PCPs in the NCE-CPDC examination(improving by 1%–6.13%).In summary,LLMs demonstrated outstanding competence for diabetes-related questions in both the Chinese and English language,and hold great potential to assist future diabetes training for physicians globally.展开更多
Background:The convergence of smartphone technology and artificial intelligence(AI)has revolutionized the landscape of ophthalmic care,offering unprecedented opportunities for diagnosis,monitoring,and management of oc...Background:The convergence of smartphone technology and artificial intelligence(AI)has revolutionized the landscape of ophthalmic care,offering unprecedented opportunities for diagnosis,monitoring,and management of ocular conditions.Nevertheless,there is a lack of systematic studies on discussing the integration of smart-phone and AI in this field.Main text:This review includes 52 studies,and explores the integration of smartphones and AI in ophthalmology,delineating its collective impact on screening methodologies,disease detection,telemedicine initiatives,and patient management.The collective findings from the curated studies indicate promising performance of the smartphone-based AI screening for various ocular diseases which encompass major retinal diseases,glaucoma,cataract,visual impairment in children and ocular surface diseases.Moreover,the utilization of smartphone-based imaging modalities,coupled with AI algorithms,is able to provide timely,efficient and cost-effective screening for ocular pathologies.This modality can also facilitate patient self-monitoring,remote patient monitoring and enhancing accessibility to eye care services,particularly in underserved regions.Challenges involving data pri-vacy,algorithm validation,regulatory frameworks and issues of trust are still need to be addressed.Furthermore,evaluation on real-world implementation is imperative as well,and real-world prospective studies are currently lacking.Conclusions:Smartphone ocular imaging merged with AI enables earlier,precise diagnoses,personalized treat-ments,and enhanced service accessibility in eye care.Collaboration is crucial to navigate ethical and data security challenges while responsibly leveraging these innovations,promising a potential revolution in care access and global eye health equity.展开更多
In two recent articles published in Nature Neuroscience and Cell,Nelson et al.1 and Chen et al.2 have shown that a rare APOE3 Christchurch(APOE3Ch)variant,R136S,has protective effects on neurodegeneration in various A...In two recent articles published in Nature Neuroscience and Cell,Nelson et al.1 and Chen et al.2 have shown that a rare APOE3 Christchurch(APOE3Ch)variant,R136S,has protective effects on neurodegeneration in various Alzheimer’s disease(AD)model systems through attenuating tau pathology and regulating its related neuroimmune responses.Nelson et al.and Chen et al.have provided evidence that identifying the pathophysiologic clues and potential molecular targets from a protective variant such as APOE R136S,can be an attractive viable approach to develop AD therapeutics.展开更多
Background and Aims:As practice patterns and hepatitis C virus(HCV)genotypes(GT)vary geographically,a global real-world study from both East and West covering all GTs can help inform practice policy toward the 2030 HC...Background and Aims:As practice patterns and hepatitis C virus(HCV)genotypes(GT)vary geographically,a global real-world study from both East and West covering all GTs can help inform practice policy toward the 2030 HCV elimination goal.This study aimed to assess the effectiveness and tolerability of DAA treatment in routine clinical practice in a multinational cohort for patients infected with all HCV GTs,focusing on GT3 and GT6.Methods:We analyzed the sustained virological response(SVR12)of 15,849 chronic hepatitis C patients from 39 Real-World Evidence from the Asia Liver Consortium for HCV clinical sites in Asia Pacific,North America,and Europe between 07/01/2014–07/01/2021.Results:The mean age was 62±13 years,with 49.6%male.The demographic breakdown was 91.1%Asian(52.9%Japanese,25.7%Chinese/Taiwan residents,5.4%Korean,3.3%Malaysian,and 2.9%Vietnamese),6.4%White,1.3%Hispanic/Latino,and 1%Black/African-American.Additionally,34.8%had cirrhosis,8.6%had hepatocellular carcinoma(HCC),and 24.9%were treatment-experienced(20.7%with interferon,4.3%with direct-acting antivirals).The largest group was GT1(10,246[64.6%]),followed by GT2(3,686[23.2%]),GT3(1,151[7.2%]),GT6(457[2.8%]),GT4(47[0.3%]),GT5(1[0.006%]),and untyped GTs(261[1.6%]).The overall SVR12 was 96.9%,with rates over 95%for GT1/2/3/6 but 91.5%for GT4.SVR12 for GT3 was 95.1%overall,98.2%for GT3a,and 94.0%for GT3b.SVR12 was 98.3%overall for GT6,lower for patients with cirrhosis and treatment-experienced(TE)(93.8%)but≥97.5%for tretment-naive patients regardless of cirrhosis status.On multivariable analysis,advanced age,prior treatment failure,cirrhosis,active HCC,and GT3/4 were independent predictors of lower SVR12,while being Asian was a significant predictor of achieving SVR12.Conclusions:In this diverse multinational realworld cohort of patients with various GTs,the overall cure rate was 96.9%,despite large numbers of patients with cirrhosis,HCC,TE,and GT3/6.SVR12 for GT3/6 with cirrhosis and TE was lower but still excellent(>91%).展开更多
Diabetic retinopathy(DR)is a leading cause of vision-loss globally.Of an estimated 285 million people with diabetes mellitus worldwide,approximately one third have signs of DR and of these,a further one third of DR is...Diabetic retinopathy(DR)is a leading cause of vision-loss globally.Of an estimated 285 million people with diabetes mellitus worldwide,approximately one third have signs of DR and of these,a further one third of DR is vision-threatening DR,including diabetic macular edema(DME).The identification of established modifiable risk factors for DR such as hyperglycemia and hypertension has provided the basis for risk factor control in preventing onset and progression of DR.Additional research investigating novel risk factors has improved our understanding of multiple biological pathways involved in the pathogenesis of DR and DME,especially those involved in inflammation and oxidative stress.Variations in DR prevalence between populations have also sparked interest in genetic studies to identify loci associated with disease susceptibility.In this review,major trends in the prevalence,incidence,progression and regression of DR and DME are explored,and gaps in literature identified.Established and novel risk factors are also extensively reviewed with a focus on landmark studies and updates from the recent literature.展开更多
Bacterial infections and multidrug-resistant bacteria are major health burdens in wound care.Biocompatible antimicrobial agents,e.g.,ε-polylysine(ε-PL),provide a broad spectrum of antibacterial properties and suppor...Bacterial infections and multidrug-resistant bacteria are major health burdens in wound care.Biocompatible antimicrobial agents,e.g.,ε-polylysine(ε-PL),provide a broad spectrum of antibacterial properties and support dermal cell growth.Here,ε-PL was incorporated into polycaprolactone(PCL)/gelatin electrospun scaffolds collected at varying rotation speeds.Then,the samples were crosslinked using dopamine hydrochloride to provide highly proliferative dressings with broad antimicrobial activity.The morphological study showed that the electrospun wound dressings were smooth,continuous,and bead-free,with a mean diameter ranging from 267±7 to 331±8 nm for all random and aligned nanofibers.The fiber alignment of the electrospun PCL/gelatin scaffolds improved their tensile strength and modulus.Moreover,nanofiber mats are highly hydro-philic,which is crucial for an efficient wound dressing.The samples also demonstrated high antimicrobial properties against common wound bacterial strains,including methicillin-resistant Staphylococcus aureus(MRSA),Staphylococcus aureus(SA),Escherichia coli(EC),Acinetobacter baumannii(AB),and Pseudomonas aeruginosa(PA).Mammalian cell prolifera-tion and morphology assays involving primary human dermal fibroblasts(hDFs)and immortalized keratinocytes(HaCaT)showed excellent biocompatibility of the electrospun mats and remarkably aligned mats.Furthermore,aligned mats showed more cell migration than randomly oriented mats,which is desirable for more efficient wound healing.Therefore,it can be concluded that aligned PCL/gelatin mats containingε-PL are promising for potential use in wound dressings.展开更多
Objective:To determine the prevalence,factors associated with and patterns of concomitant Chinese medicine(CM)with Western treatment use among patients with rheumatoid arthritis(RA)in a tertiary referral centre(Singap...Objective:To determine the prevalence,factors associated with and patterns of concomitant Chinese medicine(CM)with Western treatment use among patients with rheumatoid arthritis(RA)in a tertiary referral centre(Singapore General Hospital)in Singapore.Methods:We conducted a cross-sectional intervieweradministered survey of a consecutive sample of patients with RA in Singapore General Hospital centre regarding their CM use including data on patient demographics,disease characteristics,concomitant use of CM and reasons,concerns and disclosure patterns from March to August 2015.Univariate and multivariate logistic regression analyses were performed to determine the associations of CM use.Results:Prevalence of CM use among the 258 patients surveyed(male:female 42:216;Chinese:Malay:Indian 191:29:34;mean age:61 years;mean duration of RA:10 years)was 46.1%(119/258).On muutivariate analysis,Chinese ethnicity(OR,95%CI:4.11,1.49-11.36),Chinese speakers(OR,95%CI:2.35,1.03-5.54),middle-income group(OR,95%CI:2.53,1.01-6.31)and greater learned helplessness(OR,95%CI:1.13,1.04-1.22)were significantly associated with CM use.More CM users disclosed their CM use to CM physicians(87.3%,96/110),sought advice from them on treatment interactions(59.4%,57/96)and how best to combine treatments(49.0%,47/96)than did so with rheumatologists(42.0%,50/119;40.0%,20/50;and 42.0%,21/50,respectively).Forty-two percentage(29/69)of patients who concealed CM use from rheumatologists because their rheumatologists did not specifically enquire about CM use.Conclusions:Concomitant CM use among patients with RA treated in a tertiary referral centre in Singapore is high but voluntary disclosure is low.The associations identified can help doctors identify and enquire about CM use,minimizing potential adverse interactions.展开更多
The Hong Kong Nasopharyngeal Carcinoma(NPC)Study Group 0501 trial(HK0501)is the first trial that directly compares induction(IC)versus adjuvant chemotherapy(AC)both given together with concurrent chemoradiation(CCRT)t...The Hong Kong Nasopharyngeal Carcinoma(NPC)Study Group 0501 trial(HK0501)is the first trial that directly compares induction(IC)versus adjuvant chemotherapy(AC)both given together with concurrent chemoradiation(CCRT)treatment,which long has been a contentious issue[1].Its most salient finding is that when adjusted for platinum doses and other significant factors,the timing of the chemotherapy sequence is not important.In the era where chemotherapy is administered at maximum tolerated doses(MTD),the induction strategy has the advantage because of better tolerability.On the other hand,with the realization that there may be more ways to skin a cat,adjuvant metronomic chemotherapy has gained traction at the 2021 American Society of Clinical Oncology(ASCO)meeting[2]and provides an alternative to the decades’old dogma of MTD.Metronomic chemotherapy works by exerting an anti-angiogenic effect[3-6]and also has immune effects like removing regulatory T cells(Tregs)[7]and myeloid-derived suppressor cells(MDSCs)from the tumour microenvironment[8]and causing dendritic cell maturation,which upregulates and primes the anti-tumor T cell immune response[9,10].Pediatricians are probably the first to successfully incorporate 2 years of maintenance metronomic chemotherapy in their childhood acute lymphoblastic leukaemia protocols[11]which now boast cure rates of over 90%[12].展开更多
Nonalcoholic fatty liver disease(NAFLD)exhibits sexual dimorphism,with men being more exposed than women to the risk of simple steatosis,nonalcoholic steatohepatitis fibrosis,and hepatocellular carcinoma(HCC),while th...Nonalcoholic fatty liver disease(NAFLD)exhibits sexual dimorphism,with men being more exposed than women to the risk of simple steatosis,nonalcoholic steatohepatitis fibrosis,and hepatocellular carcinoma(HCC),while the protection conferred to women seemingly disappears with aging and reproductive senescence(i.e.,menopause).HCC,the most common primary liver cancer,which carries an ominous prognosis,may result from various genetic and non-genetic risk factors.NAFLD is now projected to become the most common cause of HCC.HCC also exhibits a definite sexual dimorphism in as much as it has a worldwide high male-to-female ratio.In this review article,we focus on sex differences in the epidemiological features of HCC.Moreover,we discuss sex differences in the clinical outcome and molecular pathobiology of NAFLD-HCC.By highlighting the research gaps to be filled,the aim of this review is to prompt future research of sex differences in HCC and facilitate developing personalized cancer prevention strategies,detection,and treatments to achieve better patient outcomes in NAFLD-HCC,considering sex differences in HCC pathobiology.展开更多
文摘Corneal neuromas,also termed microneuromas,refer to microscopic,irregula rly-shaped enlargements of terminal subbasal nerve endings at sites of nerve damage or injury.The formation of corneal neuromas results from damage to corneal nerves,such as following corneal pathology or corneal or intraocular surge ries.Initially,denervated areas of sensory nerve fibers become invaded by sprouts of intact sensory nerve fibers,and later injured axons regenerate and new sprouts called neuromas develop.In recent years,analysis of corneal nerve abnormalities including corneal neuromas which can be identified using in vivo confocal microscopy,a non-invasive imaging technique with microscopic resolution,has been used to evaluate corneal neuropathy and ocular surface dysfunction.Corneal neuromas have been shown to be associated with clinical symptoms of discomfort and dryness of eyes,and are a promising surrogate biomarker for ocular surface diseases,such as neuropathic corneal pain,dry eye disease,diabetic corneal neuropathy,neurotrophic keratopathy,Sjogren's syndrome,bullous keratopathy,post-refra ctive surgery,and others.In this review,we have summarized the current literature on the association between these ocular surface diseases and the presentation of corneal microneuromas,as well as elaborated on their pathogenesis,visualization via in vivo confocal microscopy,and utility in monitoring treatment efficacy.As current quantitative analysis on neuromas mainly relies on manual annotation and quantification,which is user-dependent and labor-intensive,future direction includes the development of artificial intelligence software to identify and quantify these potential imaging biomarkers in a more automated and sensitive manner,allowing it to be applied in clinical settings more efficiently.Combining imaging and molecular biomarkers may also help elucidate the associations between corneal neuromas and ocular surface diseases.
文摘Diabetic corneal neuropathy and diabetic retinopathy are ocular complications occurring in the context of diabetes mellitus.Diabetic corneal neuropathy refers to the progressive damage of corneal nerves.Diabetic retinopathy has traditionally been considered as damage to the retinal microvasculature.However,growing evidence suggests that diabetic retinopathy is a complex neurovascular disorder resulting from dysfunction of the neurovascular unit,which includes both the retinal vascular structures and neural tissues.Diabetic retinopathy is one of the leading causes of blindness and is frequently screened for as part of diabetic ocular screening.However,diabetic corneal neuropathy is commonly overlooked and underdiagnosed,leading to severe ocular surface impairment.Several studies have found that these two conditions tend to occur together,and they share similarities in their pathogenesis pathways,being triggered by a status of chronic hyperglycemia.This review aims to discuss the interconnection between diabetic corneal neuropathy and diabetic retinopathy,whether diabetic corneal neuropathy precedes diabetic retinopathy,as well as the relation between the stage of diabetic retinopathy and the severity of corneal neuropathy.We also endeavor to explore the relevance of a corneal screening in diabetic eyes and the possibility of using corneal nerve measurements to monitor the progression of diabetic retinopathy.
文摘Laser refractive surgery is one of the most commonly performed procedures worldwide.In laser refractive surgery,Femtosecond Laser in Situ Keratomileusis and Refractive Lenticule Extraction have emerged as promising alternatives to microkeratome Laser in Situ Keratomileusis and Photorefractive Keratectomy.Following laser refractive surgery,the corneal nerves,epithelial and stromal cells release neuromediators,including neurotrophins,neuropeptides and neurotransmitters.Notably,nerve growth factor,substance P,calcitonin gene-related peptide and various cytokines are important mediators of neurogenic inflammation and corneal nerve regeneration.Alterations in neuromediator profiles and ocular surface parameters following laser refractive surgery are attributed to the surgical techniques and the severity of tissue insult induced.In this review,we will discuss the(1)Functions of neuromediators and their physiological and clinical significance;(2)Changes in the neuromediators following various laser refractive surgeries;(3)Correlation between neuromediators,ocular surface health and corneal nerve status;and(4)Future directions,including the use of neuromediators as potential biomarkers for ocular surface health following laser refractive surgery,and as adjuncts to aid in corneal regeneration after laser refractive surgery.
文摘Diabetic neuropathy is a prevalent microvascular complication of diabetes mellitus,affecting nerves in all parts of the body including corneal nerves and peripheral nervous system,leading to diabetic corneal neuropathy and diabetic peripheral neuropathy,respectively.Diabetic peripheral neuropathy is diagnosed in clinical practice using electrophysiological nerve conduction studies,clinical scoring,and skin biopsies.However,these diagnostic methods have limited sensitivity in detecting small-fiber disease,hence they do not accurately reflect the status of diabetic neuropathy.More recently,analysis of alterations in the corneal nerves has emerged as a promising surrogate marker for diabetic peripheral neuropathy.In this review,we will discuss the relationship between diabetic corneal neuropathy and diabetic peripheral neuropathy,elaborating on the foundational aspects of each:pathogenesis,clinical presentation,evaluation,and management.We will further discuss the relevance of diabetic corneal neuropathy in detecting the presence of diabetic peripheral neuropathy,particularly early diabetic peripheral neuropathy;the correlation between the severity of diabetic corneal neuropathy and that of diabetic peripheral neuropathy;and the role of diabetic corneal neuropathy in the stratification of complications of diabetic peripheral neuropathy.
基金supported by the National Medical Research Council Singapore Transition Award (Grant No. NMRC/TA/0030/2014)the Duke-NUS Oncology Academic Program Proton Therapy Research Program Fund
文摘The detection of Epstein-Barr virus(EBV)in nasopharyngeal carcinoma(NPC)has evolved over the last40 years,transitioning from simple serological tests of latent viral infection to extremely sensitive measurements of
文摘Small Aδand C nerve fibers of the sensory and autonomic nervous systems constitute 70–90%of peripheral nerve fibers including corneal nerves(Muller et al.,2003).Corneal nerves originate from the ophthalmic branch of the trigeminal nerve and enter the cornea at the limbus radially from all directions toward the central cornea at the level of anterior and middle stroma.The subepithelial nerve plexus lies at the interface between the Bowman layer and anterior stroma.They then divide into smaller branches and turn 90°toward Bowman’s layer(Muller et al.,2003),travelling between Bowman’s layer and the basal epithelial layer and forming the sub-basal nerve plexus(Muller et al.,2003).
基金Supported by the Ministry of Higher Education Malaysia for the Fundamental Research Grant Scheme,No. FRGS/1/2021/SKK06/USM/02/7
文摘BACKGROUND The development of new vasculatures(angiogenesis)is indispensable in supplying oxygen and nutrients to fuel tumor growth.Epigenetic dysregulation in the tumor vasculature is critical to colorectal cancer(CRC)progression.Sirtuin(SIRT)enzymes are highly expressed in blood vessels.BZD9L1 benzimidazole analogue is a SIRT 1 and 2 inhibitor with reported anticancer activities in CRC.However,its role has yet to be explored in CRC tumor angiogenesis.AIM To investigate the anti-angiogenic potential of BZD9L1 on endothelial cells(EC)in vitro,ex vivo and in HCT116 CRC xenograft in vivo models.METHODS EA.hy926 EC were treated with half inhibitory concentration(IC50)(2.5μM),IC50(5.0μM),and double IC50(10.0μM)of BZD9L1 and assessed for cell proliferation,adhesion and SIRT 1 and 2 protein expression.Next,2.5μM and 5.0μM of BZD9L1 were employed in downstream in vitro assays,including cell cycle,cell death and sprouting in EC.The effect of BZD9L1 on cell adhesion molecules and SIRT 1 and 2 were assessed via real-time quantitative polymerase chain reaction(qPCR).The growth factors secreted by EC post-treatment were evaluated using the Quantibody Human Angiogenesis Array.Indirect co-culture with HCT116 CRC cells was performed to investigate the impact of growth factors modulated by BZD9L1-treated EC on CRC.The effect of BZD9L1 on sprouting impediment and vessel regression was determined using mouse choroids.HCT116 cells were also injected subcutaneously into nude mice and analyzed for the outcome of BZD9L1 on tumor necrosis,Ki67 protein expression indicative of proliferation,cluster of differentiation 31(CD31)and CD34 EC markers,and SIRT 1 and 2 genes via hematoxylin and eosin,immunohistochemistry and qPCR,respectively.RESULTS BZD9L1 impeded EC proliferation,adhesion,and spheroid sprouting through the downregulation of intercellular adhesion molecule 1,vascular endothelial cadherin,integrin-alpha V,SIRT1 and SIRT2 genes.The compound also arrested the cells at G1 phase and induced apoptosis in the EC.In mouse choroids,BZD9L1 inhibited sprouting and regressed sprouting vessels compared to the negative control.Compared to the negative control,the compound also reduced the protein levels of angiogenin,basic fibroblast growth factor,platelet-derived growth factor and placental growth factor,which then inhibited HCT116 CRC spheroid invasion in co-culture.In addition,a significant reduction in CRC tumor growth was noted alongside the downregulation of human SIRT1(hSIRT1),hSIRT2,CD31,and CD34 EC markers and murine SIRT2 gene,while the murine SIRT1 gene remained unaffected,compared to vehicle control.Histology analyses revealed that BZD9L1 at low(50 mg/kg)and high(250 mg/kg)doses reduced Ki-67 protein expression,while BZD9L1 at the high dose diminished tumor necrosis compared to vehicle control.CONCLUSION These results highlighted the anti-angiogenic potential of BZD9L1 to reduce CRC tumor progression.Furthermore,together with previous anticancer findings,this study provides valuable insights into the potential of BZD9L1 to co-target CRC tumor vasculatures and cancer cells via SIRT1 and/or SIRT2 down-regulation to improve the therapeutic outcome.
基金Supported by the Nurturing Clinician Scientist Scheme(NCCS)award by SingHealth Duke-NUS Academic Medical Centre and National Medical Research Council Singapore.
文摘BACKGROUND Hepatitis C virus(HCV)is a leading cause of liver cirrhosis and hepatocellular carcinoma globally.Sofosbuvir/velpatasvir(SOF/VEL)is an effective pangenotypic direct-acting antiviral combination for treatment of chronic HCV infection.While the addition of ribavirin(RBV)to SOF/VEL improved sustained virological response(SVR12)in genotype 3(GT3)decompensated cirrhosis patients,the benefits of RBV in GT3 compensated cirrhosis patients receiving SOF/VEL remains unclear.AIM To evaluate the efficacy and safety of SOF/VEL,with or without RBV in GT3 compensated cirrhosis patients.METHODS We searched four electronic databases(PubMed/Medline,Embase,Cochrane Library and Web of Science)from inception up to June 2021 using both free text and MeSH terms.There was no restriction on language,geography,publication dates and publication status(full text or abstracts).All GT3 compensated cirrhosis patients treated with 12 wk of SOF/VEL,with or without RBV,were included,regardless of age,gender or prior treatment experience.The primary outcome was sustained virological response 12-wk posttreatment(SVR12).The secondary outcome was treatment-related adverse events,as defined by symptomatic anemia requiring transfusion or a drop in hemoglobin beyond 2 g/dL.The pooled relative risk(RR),95%CI and heterogeneity(I^(2))were estimated using Review Manager version 5.3.RESULTS From 1752 citations,a total of seven studies(2 randomized controlled trials,5 cohort studies)with 1088 subjects were identified.The SVR12 was similar in GT3 compensated cirrhosis patients,regardless of the use of RBV,for both the intention-to-treat RR 1.03,95%CI:0.99-1.07;I^(2)=0%)and the per-protocol analysis(RR:1.03,95%CI:0.99-1.07;I^(2)=48%).The overall pooled rate of treatment-related adverse events was 7.2%.Addition of RBV increased the pooled risk of treatment-related adverse events in GT3 compensated cirrhosis patients receiving SOF/VEL(RR:4.20,95%CI:1.29-13.68;I^(2)=0%).Subgroup analysis showed that RBV was associated with a higher SVR12 in GT3 compensated cirrhosis patients with baseline resistance-associated substitutions.However,addition of RBV did not significantly increase the SVR12 among treatment-experienced GT3 compensated cirrhosis patients.CONCLUSION Ribavirin was not associated with higher SVR12 in GT3 compensated cirrhosis patients receiving SOF/VEL.Our findings suggest a limited role for RBV as routine add-on therapy to SOF/VEL in GT3 compensated cirrhosis patients.
文摘Submacular haemorrhage(SMH)is a sight threatening complication that can occur in exudative age related macular degeneration(AMD),but has been described to occur more frequently in eyes with polypoidal choroidal vasculopathy(PCV).Left untreated,SMH carries a grave visual prognosis.Thus,expedient diagnosis and effective management of this complication is of paramount importance.The treatment strategies for SMH include(I)displacement of blood from the fovea,usually by injection of an expansile gas;(II)pharmacologic clot lysis such as with recombinant tissue plasminogen activator(rtPA);and(III)treatment of the underlying choroidal neovascularization(CNV)or PCV,such as with anti-vascular endothelial growth factor(anti-VEGF)agents.These three strategies have been employed in isolation or in combination,some concurrently and others in stages.rtPA has demonstrable effect on the liquefaction of submacular clots but there are remaining uncertainties with regards to the dose,safety and the timing of initial and repeat treatments.Potential side effects of rtPA include retinal pigment epithelial toxicity,increased risk of breakthrough vitreous haemorrhage and systemic toxicity.In cases presenting early,pneumatic displacement alone with anti-VEGF may be sufficient.Anti-VEGF monotherapy is a viable treatment option particularly in patients with thinner SMH and those who are unable to posture post pneumatic displacement.
文摘Retinal angiogenic diseases,such as diabetic retinopathy(DR)and age-related macular degeneration(AMD)represent the leading causes of vision impairment in developed countries.There is strong evidence that dysregulated metabolic pathways contribute to DR as known risk factors do not explain all cases and the phenomenon of metabolic memory persists for decades or longer.Some early studies also showed that changes of plasma metabolic profiles are associated with AMD.Metabolic abnormalities can be explored using the techniques of the new science of metabolomics.In this presentation,several metabolomics workflows as well as the application of data independent acquisition mass spectrometry(DIA-MS)in metabolomics will be discussed.Our recent findings from metabolomics studies on DR and AMD will be presented.
基金supported by the Noncommunicable Chronic Diseases-National Science and Technology Major Project(2023ZD0509202 and 2023ZD0509201)National Natural Science Foundation of China(62077037,8238810007,82022012,81870598,62272298 and 82388101)+4 种基金the National Key Research and Development Program of China(2022YFC2502800 and 2022YFC2407000)the Shanghai Municipal Key Clinical Specialty,Shanghai Research Center for Endocrine and Metabolic Diseases(2022ZZ01002)the Chinese Academy of Engineering(2022-XY-08)the Innovative Research Team of High-level Local Universities in Shanghai(SHSMUZDCX20212700)Beijing Natural Science Foundation(IS23096).
文摘Diabetes poses a considerable global health challenge,with varying levels of diabetes knowledge among healthcare professionals,highlighting the importance of diabetes training.Large Language Models(LLMs)provide new insights into diabetes training,but their performance in diabetes-related queries remains uncertain,especially outside the English language like Chinese.We first evaluated the performance of ten LLMs:ChatGPT-3.5,ChatGPT-4.0,Google Bard,LlaMA-7B,LlaMA2-7B,Baidu ERNIE Bot,Ali Tongyi Qianwen,MedGPT,HuatuoGPT,and Chinese LlaMA2-7B on diabetes-related queries,based on the Chinese National Certificate Examination for Primary Diabetes Care in China(NCE-CPDC)and the English Specialty Certificate Examination in Endocrinology and Diabetes of Membership of the Royal College of Physicians of the United Kingdom.Second,we assessed the training of primary care physicians(PCPs)without and with the assistance of ChatGPT-4.0 in the NCE-CPDC examination to ascertain the reliability of LLMs as medical assistants.We found that ChatGPT-4.0 outperformed other LLMs in the English examination,achieving a passing accuracy of 62.50%,which was significantly higher than that of Google Bard,LlaMA-7B,and LlaMA2-7B.For the NCE-CPFC examination,ChatGPT-4.0,Ali Tongyi Qianwen,Baidu ERNIE Bot,Google Bard,MedGPT,and ChatGPT-3.5 successfully passed,whereas LlaMA2-7B,HuatuoGPT,Chinese LLaMA2-7B,and LlaMA-7B failed.ChatGPT-4.0(84.82%)surpassed all PCPs and assisted most PCPs in the NCE-CPDC examination(improving by 1%–6.13%).In summary,LLMs demonstrated outstanding competence for diabetes-related questions in both the Chinese and English language,and hold great potential to assist future diabetes training for physicians globally.
基金supported by Natural Science Foundation of China(grant number 82201195)Clinical Medical Research Center for Eye Diseases of Zhejiang Province(grant number 2021E50007).
文摘Background:The convergence of smartphone technology and artificial intelligence(AI)has revolutionized the landscape of ophthalmic care,offering unprecedented opportunities for diagnosis,monitoring,and management of ocular conditions.Nevertheless,there is a lack of systematic studies on discussing the integration of smart-phone and AI in this field.Main text:This review includes 52 studies,and explores the integration of smartphones and AI in ophthalmology,delineating its collective impact on screening methodologies,disease detection,telemedicine initiatives,and patient management.The collective findings from the curated studies indicate promising performance of the smartphone-based AI screening for various ocular diseases which encompass major retinal diseases,glaucoma,cataract,visual impairment in children and ocular surface diseases.Moreover,the utilization of smartphone-based imaging modalities,coupled with AI algorithms,is able to provide timely,efficient and cost-effective screening for ocular pathologies.This modality can also facilitate patient self-monitoring,remote patient monitoring and enhancing accessibility to eye care services,particularly in underserved regions.Challenges involving data pri-vacy,algorithm validation,regulatory frameworks and issues of trust are still need to be addressed.Furthermore,evaluation on real-world implementation is imperative as well,and real-world prospective studies are currently lacking.Conclusions:Smartphone ocular imaging merged with AI enables earlier,precise diagnoses,personalized treat-ments,and enhanced service accessibility in eye care.Collaboration is crucial to navigate ethical and data security challenges while responsibly leveraging these innovations,promising a potential revolution in care access and global eye health equity.
基金Singapore Ministry of Health’s National Medical Research Council for their support(Open Fund Large Collaborative Grant(MOH-000207)Singapore Translational Research(STaR)Investigator Award(NMRC/STaR/0030/2018)to E.-K.T.,TA award and OF-YIRG to B.X.)。
文摘In two recent articles published in Nature Neuroscience and Cell,Nelson et al.1 and Chen et al.2 have shown that a rare APOE3 Christchurch(APOE3Ch)variant,R136S,has protective effects on neurodegeneration in various Alzheimer’s disease(AD)model systems through attenuating tau pathology and regulating its related neuroimmune responses.Nelson et al.and Chen et al.have provided evidence that identifying the pathophysiologic clues and potential molecular targets from a protective variant such as APOE R136S,can be an attractive viable approach to develop AD therapeutics.
基金partially supported by an investigator-initiated research grant(IN-US-334-4309)from Gilead Sciences to Stanford University.
文摘Background and Aims:As practice patterns and hepatitis C virus(HCV)genotypes(GT)vary geographically,a global real-world study from both East and West covering all GTs can help inform practice policy toward the 2030 HCV elimination goal.This study aimed to assess the effectiveness and tolerability of DAA treatment in routine clinical practice in a multinational cohort for patients infected with all HCV GTs,focusing on GT3 and GT6.Methods:We analyzed the sustained virological response(SVR12)of 15,849 chronic hepatitis C patients from 39 Real-World Evidence from the Asia Liver Consortium for HCV clinical sites in Asia Pacific,North America,and Europe between 07/01/2014–07/01/2021.Results:The mean age was 62±13 years,with 49.6%male.The demographic breakdown was 91.1%Asian(52.9%Japanese,25.7%Chinese/Taiwan residents,5.4%Korean,3.3%Malaysian,and 2.9%Vietnamese),6.4%White,1.3%Hispanic/Latino,and 1%Black/African-American.Additionally,34.8%had cirrhosis,8.6%had hepatocellular carcinoma(HCC),and 24.9%were treatment-experienced(20.7%with interferon,4.3%with direct-acting antivirals).The largest group was GT1(10,246[64.6%]),followed by GT2(3,686[23.2%]),GT3(1,151[7.2%]),GT6(457[2.8%]),GT4(47[0.3%]),GT5(1[0.006%]),and untyped GTs(261[1.6%]).The overall SVR12 was 96.9%,with rates over 95%for GT1/2/3/6 but 91.5%for GT4.SVR12 for GT3 was 95.1%overall,98.2%for GT3a,and 94.0%for GT3b.SVR12 was 98.3%overall for GT6,lower for patients with cirrhosis and treatment-experienced(TE)(93.8%)but≥97.5%for tretment-naive patients regardless of cirrhosis status.On multivariable analysis,advanced age,prior treatment failure,cirrhosis,active HCC,and GT3/4 were independent predictors of lower SVR12,while being Asian was a significant predictor of achieving SVR12.Conclusions:In this diverse multinational realworld cohort of patients with various GTs,the overall cure rate was 96.9%,despite large numbers of patients with cirrhosis,HCC,TE,and GT3/6.SVR12 for GT3/6 with cirrhosis and TE was lower but still excellent(>91%).
文摘Diabetic retinopathy(DR)is a leading cause of vision-loss globally.Of an estimated 285 million people with diabetes mellitus worldwide,approximately one third have signs of DR and of these,a further one third of DR is vision-threatening DR,including diabetic macular edema(DME).The identification of established modifiable risk factors for DR such as hyperglycemia and hypertension has provided the basis for risk factor control in preventing onset and progression of DR.Additional research investigating novel risk factors has improved our understanding of multiple biological pathways involved in the pathogenesis of DR and DME,especially those involved in inflammation and oxidative stress.Variations in DR prevalence between populations have also sparked interest in genetic studies to identify loci associated with disease susceptibility.In this review,major trends in the prevalence,incidence,progression and regression of DR and DME are explored,and gaps in literature identified.Established and novel risk factors are also extensively reviewed with a focus on landmark studies and updates from the recent literature.
基金support from the Singapore International Graduate Award(SINGA).R.L.thanks funding support from the Duke-NUS Khoo Bridge Funding Award(Duke-NUS-KBrFA/2021/0044)N.K.V.acknowledges funding support from the Singapore Ministry of Education(MOE)under its MOE Academic Research Fund(AcRF)Tier 1 Grant(RG26/20)the Agency for Science,Technology and Research(A*STAR)under its Wound Care Innovation for the Tropics(WCIT)Industry Alignment Fund Pre-Positioning(IAF-PP)Grant(H17/01/a0/0K9)。
文摘Bacterial infections and multidrug-resistant bacteria are major health burdens in wound care.Biocompatible antimicrobial agents,e.g.,ε-polylysine(ε-PL),provide a broad spectrum of antibacterial properties and support dermal cell growth.Here,ε-PL was incorporated into polycaprolactone(PCL)/gelatin electrospun scaffolds collected at varying rotation speeds.Then,the samples were crosslinked using dopamine hydrochloride to provide highly proliferative dressings with broad antimicrobial activity.The morphological study showed that the electrospun wound dressings were smooth,continuous,and bead-free,with a mean diameter ranging from 267±7 to 331±8 nm for all random and aligned nanofibers.The fiber alignment of the electrospun PCL/gelatin scaffolds improved their tensile strength and modulus.Moreover,nanofiber mats are highly hydro-philic,which is crucial for an efficient wound dressing.The samples also demonstrated high antimicrobial properties against common wound bacterial strains,including methicillin-resistant Staphylococcus aureus(MRSA),Staphylococcus aureus(SA),Escherichia coli(EC),Acinetobacter baumannii(AB),and Pseudomonas aeruginosa(PA).Mammalian cell prolifera-tion and morphology assays involving primary human dermal fibroblasts(hDFs)and immortalized keratinocytes(HaCaT)showed excellent biocompatibility of the electrospun mats and remarkably aligned mats.Furthermore,aligned mats showed more cell migration than randomly oriented mats,which is desirable for more efficient wound healing.Therefore,it can be concluded that aligned PCL/gelatin mats containingε-PL are promising for potential use in wound dressings.
文摘Objective:To determine the prevalence,factors associated with and patterns of concomitant Chinese medicine(CM)with Western treatment use among patients with rheumatoid arthritis(RA)in a tertiary referral centre(Singapore General Hospital)in Singapore.Methods:We conducted a cross-sectional intervieweradministered survey of a consecutive sample of patients with RA in Singapore General Hospital centre regarding their CM use including data on patient demographics,disease characteristics,concomitant use of CM and reasons,concerns and disclosure patterns from March to August 2015.Univariate and multivariate logistic regression analyses were performed to determine the associations of CM use.Results:Prevalence of CM use among the 258 patients surveyed(male:female 42:216;Chinese:Malay:Indian 191:29:34;mean age:61 years;mean duration of RA:10 years)was 46.1%(119/258).On muutivariate analysis,Chinese ethnicity(OR,95%CI:4.11,1.49-11.36),Chinese speakers(OR,95%CI:2.35,1.03-5.54),middle-income group(OR,95%CI:2.53,1.01-6.31)and greater learned helplessness(OR,95%CI:1.13,1.04-1.22)were significantly associated with CM use.More CM users disclosed their CM use to CM physicians(87.3%,96/110),sought advice from them on treatment interactions(59.4%,57/96)and how best to combine treatments(49.0%,47/96)than did so with rheumatologists(42.0%,50/119;40.0%,20/50;and 42.0%,21/50,respectively).Forty-two percentage(29/69)of patients who concealed CM use from rheumatologists because their rheumatologists did not specifically enquire about CM use.Conclusions:Concomitant CM use among patients with RA treated in a tertiary referral centre in Singapore is high but voluntary disclosure is low.The associations identified can help doctors identify and enquire about CM use,minimizing potential adverse interactions.
文摘The Hong Kong Nasopharyngeal Carcinoma(NPC)Study Group 0501 trial(HK0501)is the first trial that directly compares induction(IC)versus adjuvant chemotherapy(AC)both given together with concurrent chemoradiation(CCRT)treatment,which long has been a contentious issue[1].Its most salient finding is that when adjusted for platinum doses and other significant factors,the timing of the chemotherapy sequence is not important.In the era where chemotherapy is administered at maximum tolerated doses(MTD),the induction strategy has the advantage because of better tolerability.On the other hand,with the realization that there may be more ways to skin a cat,adjuvant metronomic chemotherapy has gained traction at the 2021 American Society of Clinical Oncology(ASCO)meeting[2]and provides an alternative to the decades’old dogma of MTD.Metronomic chemotherapy works by exerting an anti-angiogenic effect[3-6]and also has immune effects like removing regulatory T cells(Tregs)[7]and myeloid-derived suppressor cells(MDSCs)from the tumour microenvironment[8]and causing dendritic cell maturation,which upregulates and primes the anti-tumor T cell immune response[9,10].Pediatricians are probably the first to successfully incorporate 2 years of maintenance metronomic chemotherapy in their childhood acute lymphoblastic leukaemia protocols[11]which now boast cure rates of over 90%[12].
文摘Nonalcoholic fatty liver disease(NAFLD)exhibits sexual dimorphism,with men being more exposed than women to the risk of simple steatosis,nonalcoholic steatohepatitis fibrosis,and hepatocellular carcinoma(HCC),while the protection conferred to women seemingly disappears with aging and reproductive senescence(i.e.,menopause).HCC,the most common primary liver cancer,which carries an ominous prognosis,may result from various genetic and non-genetic risk factors.NAFLD is now projected to become the most common cause of HCC.HCC also exhibits a definite sexual dimorphism in as much as it has a worldwide high male-to-female ratio.In this review article,we focus on sex differences in the epidemiological features of HCC.Moreover,we discuss sex differences in the clinical outcome and molecular pathobiology of NAFLD-HCC.By highlighting the research gaps to be filled,the aim of this review is to prompt future research of sex differences in HCC and facilitate developing personalized cancer prevention strategies,detection,and treatments to achieve better patient outcomes in NAFLD-HCC,considering sex differences in HCC pathobiology.
