Subretinal fibrosis secondary to neovascular age-related macular degeneration:mechanisms and potential therapeutic targets

Subretinal fibrosis is the end-stage sequelae of neovascular age-related macular degeneration.It causes local damage to photoreceptors,retinal pigment epithelium,and choroidal vessels,which leads to permanent central vision loss of patients with neovascular age-related macular degeneration.The pathogenesis of subretinal fibrosis is complex,and the underlying mechanisms are largely unknown.Therefore,there are no effective treatment options.A thorough understanding of the pathogenesis of subretinal fibrosis and its related mechanisms is important to elucidate its complications and explore potential treatments.The current article reviews several aspects of subretinal fibrosis,including the current understanding on the relationship between neovascular age-related macular degeneration and subretinal fibrosis;multimodal imaging techniques for subretinal fibrosis;animal models for studying subretinal fibrosis;cellular and non-cellular constituents of subretinal fibrosis;pathophysiological mechanisms involved in subretinal fibrosis,such as aging,infiltration of macrophages,different sources of mesenchymal transition to myofibroblast,and activation of complement system and immune cells;and several key molecules and signaling pathways participating in the pathogenesis of subretinal fibrosis,such as vascular endothelial growth factor,connective tissue growth factor,fibroblast growth factor 2,platelet-derived growth factor and platelet-derived growth factor receptor-β,transforming growth factor-βsignaling pathway,Wnt signaling pathway,and the axis of heat shock protein 70-Toll-like receptors 2/4-interleukin-10.This review will improve the understanding of the pathogenesis of subretinal fibrosis,allow the discovery of molecular targets,and explore potential treatments for the management of subretinal fibrosis.

Elafibranor:A promising therapeutic approach for liver fibrosis and gut barrier dysfunction in alcohol-associated liver disease

This article discusses the recent study written by Koizumi et al.Alcohol-associated liver disease(ALD)is a major cause of liver-related morbidity and mortality,which is driven by complex mechanisms,including lipid accumulation,apoptosis,and inflammatory responses exacerbated by gut barrier dysfunction.The study explored the therapeutic potential of elafibranor,a dual peroxisome proliferatoractivated receptor alpha/delta agonist.In clinical trials,elafibranor has shown promise for the treatment of other liver conditions;however,its effects on ALD remain unclear.The authors’findings indicate that elafibranor significantly reduced liver fibrosis and enhanced gut barrier integrity in patients with ALD.These positive effects of elafibranor are mediated through multiple pathways.Elafibranor promotes lipid metabolism,reduces oxidative stress,and inhibits inflammatory responses by restoring gut barrier function.Specifically,it improves hepatocyte function by enhancing autophagic and antioxidant capacity,and it mitigates inflammation by suppressing the lipopolysaccharide/toll-like receptor 4/nuclear factor kappa B signaling pathway.These findings indicate that elafibranor has promising clinical applications.In addition,the study highlights elafibranor’s potential as a therapeutic agent for liver diseases,particularly ALD.This article underscores the importance of understanding the mechanistic pathways underlying ALD and suggests directions for future research aimed at elucidating the benefits and limitations of elafibranor.

Importance of neonatal screening:A case study of sickle cell disease and cystic fibrosis coexistence

BACKGROUND Neonatal screening(NS)is a public health policy to identify genetic pathologies such as cystic fibrosis(CF),sickle cell disease,and other diseases.Sickle cell disea-se is the comprehensive term for a group of hemoglobinopathies characterized by the presence of hemoglobin S.CF is an autosomal recessive multisystemic disease with pathophysiology involving deleterious mutations in the transmembrane re-gulatory gene that encodes a protein that regulates the activity of chloride and sodium channels in the cell surface epithelium.NS is crucial for early diagnosis and management,which ensures a better quality of life.AIM To report a case of the coexistence of sickle cell anemia(SCA)and CF and perform an integrative literature review.METHODS This is an observational study and a review of the literature focusing on two rare genetic pathologies identified simultaneously in NS from the perspective of a clinical case.The authors identified only 5 cases of SCA associated with CF.No clinical trials or review articles were identified considering the rarity of the coexistence of these two pathologies.RESULTS Herein,the authors reported the case of a girl who after undergoing NS on day 8 of life was diagnosed with SCA with an alteration in the dosage of immunoreactive trypsin.The diagnosis of CF was confirmed by the Coulometry Sweat Test.The rarity of the co-occurrence of these two severe genetic pathologies(CF and SCA)is a challenge for medical science.CONCLUSION This study adds to the few case reports present in the literature that highlight the identification of two severe diseases via NS.

基于区块链及IPFS的农产品多链追溯系统研究

面对农产品供应市场日益庞大以及现存追溯系统中心化结构严重、溯源信息模糊简陋、数据安全难以得到有效保障等问题,通过分析供应链的业务流程及相关特点,融合区块链及IPFS技术设计灵活的多链分布式追溯系统以应对错综复杂多变的市场情况中的精准溯源及监管的需求。充分利用星际文件系统IPFS的去重存储以及分布式存储特性提高存储资源的利用率,解决以往溯源数据存储中心化严重、数据类型单一、负载过大等问题;区块链多链与IPFS私有网络的结合以及CBC、ECC两个加密算法的采用可以支持全面的市场监管,并可以满足企业隐私数据的加密保护需求。为验证模型有效性,以水培蔬菜溯源项目作为应用案例进行分析测试,其中区块链多链系统吞吐量达到上链500 TPS、查询400 TPS;CBC加密算法的相关性、扩展性分析中密文改变率分别达到96.727%、97.136%。测试结果表明:本追溯系统在实现溯源数据高效记录存储和精准监管溯源的基础上,也能够给予供应链内各方合法权益及隐私数据有效的安全保护,亦可以面对业务交错复杂的市场供应链,为完整可靠的农产品区块链追溯监管系统研究发展与落地实现提供借鉴与参考。

基于联盟链和IPFS的教育公益捐赠方案与平台设计

针对当前教育公益捐赠监管不力、资金流向不透明和信任危机等问题,提出一种基于联盟链和星际文件系统(InterPlanetary File System,IPFS)的教育公益捐赠方案,区块链的去中心化、数据不可篡改、交易透明等特点为该方案奠定了基础。首先,对该方案的应用模式进行了说明;其次,阐述了基于该方案的平台架构分层设计以及平台运行原理,以及数据加密处理、数据存储和捐赠溯源等关键技术;最后,基于该平台进行捐赠、溯源的可行性分析。分析结果表明,该平台性能更安全,吞吐量更高,溯源更高效。

基于区块链和IPFS的存储机制设计

随着物联网设备的普及和人工智能应用的落地,物联网数据的规模呈爆炸式增长。要想实现物与物、物与人之间更便捷沟通的美好愿景,必须考虑物联网海量数据的存储问题。文章设计了一种基于区块链和星际文件系统(IPFS)的存储机制,通过与传统的区块链对比,基于区块链和IPFS的存储机制为存储和管理数据提供了一种安全、分散且可扩展的解决方案。

基于区块链和IPFS的高校教学资源共享平台构建

针对目前高校教学资源共享中存在的资源激励机制欠缺、资源存储安全风险以及资源版权保护不足等问题,文章通过将星际文件系统(Inter-Planetary File System,IPFS)和区块链进行结合,实现链上索引、链下存储的教学资源存储模式。文章利用智能合约技术自动执行对教学资源版权的保护,构建了基于虚拟币的资源创作激励机制。在此基础上,文章提出了高校教学资源共享平台的总体分层架构和共享流程,并设计了平台的4大功能模块,为区块链技术在教学资源共享共建领域的应用提供了新思路。

以患者为中心基于IPFS和区块链的医疗信息共享方案

医疗机构之间的电子病历(EMR)存储与共享,对实现跨院诊断和分级诊疗至关重要,可以有效减轻患者的负担和避免重复检查。针对EMR难以安全存储和共享的问题,提出一种以患者为中心基于星际文件系统(IPFS)和区块链的EMR安全存储与高效共享(PCIB-MIS)方案。首先,应用混合加密策略,以安全存储与共享EMR,缩减加解密时间;其次,通过区块链存储EMR的密文索引;再次,结合联盟链与私有链以降低存储压力,EMR索引存于医院私有链;最后,EMR密文存放于IPFS,确保数据安全和不可篡改。当需要跨院调取EMR时,进行以联盟链为中心的跨链调用与代理重加密。安全性分析与实验结果表明,仅被授权医生可获取患者病历;与公钥加密算法RSA相比,将加解密时间降低至毫秒级别;与将EMR单一存放于区块链上的方案相比,节省了98.8%的区块存储空间。所提方案可以实现病历安全存储与共享,大幅压缩EMR加解密时间和减轻区块链存储压力。

基于IPFS的区块链物联网安全模型的设计研究

IPFS是借助BitTorrent传输技术、自我验证文件系统和P2P网络技术实现的一种新型数据传输协议,其优势在于存储成本低、运行效率高,不受宽带资源限制。本文基于IPFS技术分析如何有效设计区块链物联网安全模型,结果显示,基于IPFS所设计的区块链物联网安全模型,可降低跨网信任成本,以IPFS为底层数据库,同时为区块链提供隐私保护。

Role of IL-17 family cytokines in the progression of IPF from inflammation to fibrosis

Idiopathic pulmonary fibrosis(IPF)is a fatal chronic interstitial lung disease with no established treatment and is characterized by progressive scarring of the lung tissue and an irreversible decline in lung function.Chronic inflammation has been demonstrated to be the pathological basis of fibrosis.Emerging studies have revealed that most interleukin-17(IL-17)isoforms are essential for the mediation of acute and chronic inflammation via innate and adaptive immunity.Overexpression or aberrant expression of IL-17 cytokines contributes to various pathological outcomes,including the initiation and exacerbation of IPF.Here,we aim to provide an overview of IL-17 family members in the pathogenesis of IPF.

基于“肺毛细血管通透性”异常试论IPF中医络瘀病机之生物学基础

特发性肺纤维化近年来因其治疗成本、发病率、死亡率高而备受重视,因此寻找有效且价格低廉的治疗方法和药物已经成为有待解决的难题。络病理论治疗IPF具有独特优势,基于络病理论的指导下IPF病机认识提出“络瘀”病机贯穿IPF整个病理阶段,然其物质基础尚不清楚。本文通过对特发性肺纤维化发病机制的深入研究,梳理肺毛细血管通透性增强、肺血管渗漏在IPF病理进程中的作用,并从络病理论出发,进一步揭示IPF中医“络瘀”病机的生物学基础,为络病理论指导下“通络”治法的应用奠定基础,为以络论治IPF的中医思路提供有力科学依据,为中医药治疗IPF提供新思路。

基于IPFS和区块链技术的电力安全交易平台研究

近年来,大量新能源主体接入电力交易平台,核心业务数据量激增,导致当前集中式电力交易平台运行压力过大、数据不安全、交易不透明等问题。区块链本质上是具有去中心化特征的分布式账本,具有难以篡改、安全性高等特征。星际文件系统(Inter Planetary File System,IPFS)在区块链中的应用可以减小区块链存储的数据量,具有文件去重功能,可有效避免中心化存储存在的一些安全问题和限制。文章结合两者特点,提出一种基于IPFS和区块链技术的电力安全交易平台模型,对数据存储进行优化并建立市场信用机制。仿真实验表明,该模型能够有效缓解物理节点存储压力、提升系统运行效率、有效量化市场主体信用。

Effects of elafibranor on liver fibrosis and gut barrier function in a mouse model of alcohol-associated liver disease

BACKGROUND Alcohol-associated liver disease(ALD)is a leading cause of liver-related morbidity and mortality,but there are no therapeutic targets and modalities to prevent ALD-related liver fibrosis.Peroxisome proliferator activated receptor(PPAR)α and δ play a key role in lipid metabolism and intestinal barrier homeostasis,which are major contributors to the pathological progression of ALD.Meanwhile,elafibranor(EFN),which is a dual PPARαand PPARδagonist,has reached a phase III clinical trial for the treatment of metabolic dysfunctionassociated steatotic liver disease and primary biliary cholangitis.However,the benefits of EFN for ALD treatment is unknown.AIM To evaluate the inhibitory effects of EFN on liver fibrosis and gut-intestinal barrier dysfunction in an ALD mouse model.METHODS ALD-related liver fibrosis was induced in female C57BL/6J mice by feeding a 2.5% ethanol(EtOH)-containing Lieber-DeCarli liquid diet and intraperitoneally injecting carbon tetrachloride thrice weekly(1 mL/kg)for 8 weeks.EFN(3 and 10 mg/kg/day)was orally administered during the experimental period.Histological and molecular analyses were performed to assess the effect of EFN on steatohepatitis,fibrosis,and intestinal barrier integrity.The EFN effects on HepG2 lipotoxicity and Caco-2 barrier function were evaluated by cell-based assays.RESULTS The hepatic steatosis,apoptosis,and fibrosis in the ALD mice model were significantly attenuated by EFN treatment.EFN promoted lipolysis and β-oxidation and enhanced autophagic and antioxidant capacities in EtOH-stimulated HepG2 cells,primarily through PPARαactivation.Moreover,EFN inhibited the Kupffer cell-mediated inflammatory response,with blunted hepatic exposure to lipopolysaccharide(LPS)and toll like receptor 4(TLR4)/nuclear factor kappa B(NF-κB)signaling.EFN improved intestinal hyperpermeability by restoring tight junction proteins and autophagy and by inhibiting apoptosis and proinflammatory responses.The protective effect on intestinal barrier function in the EtOH-stimulated Caco-2 cells was predominantly mediated by PPARδ activation.CONCLUSION EFN reduced ALD-related fibrosis by inhibiting lipid accumulation and apoptosis,enhancing hepatocyte autophagic and antioxidant capacities,and suppressing LPS/TLR4/NF-κB-mediated inflammatory responses by restoring intestinal barrier function.

Staging liver fibrosis with various diffusion-weighted magnetic resonance imaging models

BACKGROUND Diffusion-weighted imaging(DWI)has been developed to stage liver fibrosis.However,its diagnostic performance is inconsistent among studies.Therefore,it is worth studying the diagnostic value of various diffusion models for liver fibrosis in one cohort.AIM To evaluate the clinical potential of six diffusion-weighted models in liver fibrosis staging and compare their diagnostic performances.METHODS This prospective study enrolled 59 patients suspected of liver disease and scheduled for liver biopsy and 17 healthy participants.All participants underwent multi-b value DWI.The main DWI-derived parameters included Mono-apparent diffusion coefficient(ADC)from mono-exponential DWI,intravoxel incoherent motion model-derived true diffusion coefficient(IVIM-D),diffusion kurtosis imaging-derived apparent diffusivity(DKI-MD),stretched exponential model-derived distributed diffusion coefficient(SEM-DDC),fractional order calculus(FROC)model-derived diffusion coefficient(FROC-D)and FROC model-derived microstructural quantity(FROC-μ),and continuous-time random-walk(CTRW)model-derived anomalous diffusion coefficient(CTRW-D)and CTRW model-derived temporal diffusion heterogeneity index(CTRW-α).The correlations between DWI-derived parameters and fibrosis stages and the parameters’diagnostic efficacy in detecting significant fibrosis(SF)were assessed and compared.RESULTS CTRW-D(r=-0.356),CTRW-α(r=-0.297),DKI-MD(r=-0.297),FROC-D(r=-0.350),FROC-μ(r=-0.321),IVIM-D(r=-0.251),Mono-ADC(r=-0.362),and SEM-DDC(r=-0.263)were significantly correlated with fibrosis stages.The areas under the ROC curves(AUCs)of the combined index of the six models for distinguishing SF(0.697-0.747)were higher than each of the parameters alone(0.524-0.719).The DWI models’ability to detect SF was similar.The combined index of CTRW model parameters had the highest AUC(0.747).CONCLUSION The DWI models were similarly valuable in distinguishing SF in patients with liver disease.The combined index of CTRW parameters had the highest AUC.

基于IPFS-DEMATEL-ISM的容器安全威胁关键战术要素研究

为解决电力能源企业“上云”引发的云原生容器安全威胁问题,提出融合区间毕达哥拉斯模糊集(IPFS)、决策试验与评价实验室(DEMATEL)和解释结构模型法(ISM)识别容器安全关键战术要素。首先,基于IPFS提取安全专家对容器入侵威胁战术要素的经验判断,其次,应用DEMATEL和ISM识别容器安全威胁的关键战术要素及要素间的层级拓扑关系。结果表明:持久化和权限提升2个战术阶段的中心度和原因度较高,在整个云原生安全威胁体系中居于核心地位,这2个阶段的安全攻击行为需持高优先级关注;执行和持久化战术阶段的威胁攻击是云原生容器安全的本质要素,初始访问、窃取凭证以及横向移动战术阶段的威胁最直接影响云原生容器安全。研究提出的IPFS-DEMATEL-ISM法相较DEMATEL-ISM和集成三角模糊数的DEMATEL-ISM法在识别容器安全威胁关键战术要素时具有更好区分度和简约解释性。

Myricetin induces M2 macrophage polarization to alleviate renal tubulointerstitial fibrosis in diabetic nephropathy via PI3K/Akt pathway

BACKGROUND Development of end-stage renal disease is predominantly attributed to diabetic nephropathy(DN).Previous studies have indicated that myricetin possesses the potential to mitigate the pathological alterations observed in renal tissue.Never-theless,the precise molecular mechanism through which myricetin influences the progression of DN remains uncertain.AIM To investigate the effects of myricetin on DN and explore its potential therapeutic mechanism.METHODS Db/db mice were administered myricetin intragastrically on a daily basis at doses of 50 mg/kg or 100 mg/kg for a duration of 12 wk.Subsequently,blood and urine indexes were assessed,along with examination of renal tissue pathology.Kidney morphology and fibrosis were evaluated using various staining techniques including hematoxylin and eosin,periodic acid–Schiff,Masson’s trichrome,and Sirius-red.Additionally,high-glucose culturing was conducted on the RAW 264.7 cell line,treated with 25 mM myricetin or co-administered with the PI3K/Akt inhibitor LY294002 for a period of 24 h.In both in vivo and in vitro settings,quantification of inflammation factor levels was conducted using western blotting,real-time qPCR and ELISA.RESULTS In db/db mice,administration of myricetin led to a mitigating effect on DN-induced renal dysfunction and fibrosis.Notably,we observed a significant reduction in expressions of the kidney injury markers kidney injury molecule-1 and neutrophil gelatinase associated lipocalin,along with a decrease in expressions of inflammatory cytokine-related factors.Furthermore,myricetin treatment effectively inhibited the up-regulation of tumor necrosis factor-alpha,interleukin-6,and interluekin-1βinduced by high glucose in RAW 264.7 cells.Additionally,myricetin modulated the M1-type polarization of the RAW 264.7 cells.Molecular docking and bioinformatic analyses revealed Akt as the target of myricetin.The protective effect of myricetin was nullified upon blocking the polarization of RAW 264.7 via inhibition of PI3K/Akt activation using LY294002.CONCLUSION This study demonstrated that myricetin effectively mitigates kidney injury in DN mice through the regulation of macrophage polarization via the PI3K/Akt signaling pathway.

Angiotensin-converting enzyme 2 alleviates liver fibrosis through the renin-angiotensin system

The present letter to the editor is related to the study titled‘Angiotensin-converting enzyme 2 improves liver fibrosis in mice by regulating autophagy of hepatic stellate cells’.Angiotensin-converting enzyme 2 can alleviate liver fibrosis by regulating autophagy of hepatic stellate cells and affecting the renin-angiotensin system.

Study on the efficacy of early treatment with pirfenidone on the lung function of patients with idiopathic pulmonary fibrosis

BACKGROUND Idiopathic pulmonary fibrosis(IPF)is classified under fibrotic interstitial pneumonia,characterized by a chronic and progressive course.The predominant clinical features of IPF include dyspnea and pulmonary dysfunction.AIM To assess the effects of pirfenidone in the early treatment of IPF on lung function in patients.METHODS A retrospective analysis was performed on 113 patients with IPF who were treated in our hospital from November 2017 to January 2023.These patients were divided into two groups:control group(n=53)and observation group(n=60).In the control group,patients received routine therapy in combination with methylprednisolone tablets,while those in the observation group received routine therapy together with pirfenidone.After applying these distinct treatment approaches to the two groups,we assessed several parameters,including the overall effectiveness of clinical therapy,the occurrence of adverse reactions(e.g.,nausea,vomiting,and anorexia),symptom severity scores,pulmonary function index levels,inflammatory marker levels,and the 6-min walk distance before and after treatment in both groups.RESULTS The observation group exhibited significantly higher rates than the control group after therapy,with a clear distinction(P<0.05).After treatment,the observation group experienced significantly fewer adverse reactions than the control group,with a noticeable difference(P<0.05).When analyzing the symptom severity scores between the two groups of patients after treatment,the observation group had significantly lower scores than the control group,with a distinct difference(P<0.05).When comparing the pulmonary function index levels between the two groups of patients after therapy,the observation group displayed significantly higher levels than the control group,with a noticeable difference(P<0.05).Evaluating the inflammatory marker data(C-reactive protein,interleukin-2[IL-2],and IL-8)between the two groups of patients after therapy,the observation group exhibited significantly lower levels than the control group,with significant disparities(P<0.05).Comparison of the 6-min walking distance data between the two groups of patients after treatment showed that the observation group achieved significantly greater distances than the control group,with a marked difference(P<0.05).CONCLUSION Prompt initiation of pirfenidone treatment in individuals diagnosed with IPF can enhance pulmonary function,elevate inflammatory factor levels,and increase the distance covered in the 6-min walk test.This intervention is conducive to effectively decreasing the occurrence of adverse reactions in patients.

Perceived Improvements of Quality of Life (QoL) among Patients with Idiopathic Pulmonary Fibrosis (IPF) in Response to a 6-Week Rehabilitation Program

Idiopathic pulmonary fibrosis (IPF) is a chronic, life-limiting with an average life expectancy of 05 years following the onset of the disease, with no curative treatments. These patients need palliative care and rehabilitation is one of the methods that can be used to improve quality of life (QoL) among these patients. Yet the research conducted to assess benefits of pulmonary rehabilitation (PR) in terms of improving physical activity and QoL in IPF patients remains limited. Hence this study aims to evaluate the effect of a bespoke pulmonary rehabilitation programme, on the physical, physiological and psychological parameters and improvements of QoL among IPF patients. Eleven (11) subjects with IPF received 6 weeks of pulmonary rehabilitation. An interviewer administered quality of life questionnaire, six-minute walking test (6MWT), Incremental bicycle exercise tests were performed, and cardiac and respiratory parameters were assessed pre- and post-rehabilitation. The 6MWT was significantly increased following training (Pre 312.55 ± 89.99;Post, 380.73 ± 59.60). A significant improvement was observed in overall QoL (2.226 ± 0.026), dyspnoea (-0.455 ± 0.004) anxiety (-2.070 ± 0.038), depression (-2.217 ± 0.027) scores. No significant changes were found in the VO2 max and other cardiopulmonary parameters, while non-significant improvement was seen in SpO2 at peak exercise from 85.8 - 86.5. Bespoke pulmonary rehabilitation program is beneficial in short term improvement of the functional exercise capacity, dyspnoea and QoL among IPF patients.

Patients’ Experiences and Opinions on Pulmonary Rehabilitation and Use of It as a Tool of Palliative Care on Idiopathic Pulmonary Fibrosis (IPF)

Background: Idiopathic Pulmonary Fibrosis (IPF) is a chronic, progressive, and life-limiting condition. It has no cure hence it is vital to establish effective methods of improving the quality of remaining life in these patients. One of the key components of improving quality of life is pulmonary rehabilitation. However little research has been conducted to understand the perspectives and lived experience of people with IPF on pulmonary rehabilitation. Hence, we aim to fill this gap in the existing literature. Methods: We sought to understand how patients coped with pulmonary rehabilitation. A patient-centred approach was used to explore the physical and psychological impact of pulmonary rehabilitation. Semi-structured interviews were conducted by experienced academics. Interviews used a topic guide but mostly led by the participants. An inductive thematic approach was used to analyse data, allowing us to identify common themes in the participants’ experiences. Results: Of fifty invited participants, ten took part in the study (aged 53 - 81 years). Inductive analysis of interviews identified seven second-order themes and eleven first-order themes, represented by two General Dimensions: “motivation” and “Advantages and disadvantages”. Overall, participants found the pulmonary rehabilitation programme to be useful and they experienced an increase in their quality of life following rehabilitation.