AIM:To observe the long-term clinical efficacy of intravitreal injections of conbercept,a novel vascular growth factor inhibitor,for the treatment of pathological myopia choroidal neovascularization(PM-CNV).METHODS:A ...AIM:To observe the long-term clinical efficacy of intravitreal injections of conbercept,a novel vascular growth factor inhibitor,for the treatment of pathological myopia choroidal neovascularization(PM-CNV).METHODS:A total of 67 eyes(from 67 patients;mean age,54.90±12.7y)with PM-CNV were retrospectively researched.Based on the different schemes used for the administration of the drug,the patients were divided into two groups:group A(n=35;average age,53.31±13.6y;average diopter,9.25±1.72 D),which received only one injection of pro re nata(PRN;1+PRN regimen),and group B(n=32;average age,56.49±11.8y;average diopter,9.63±2.24 D),which received one injection per month for 3mo(3+PRN regimen).Best-corrected visual acuity(BCVA)analysis,intraocular pressure(IOP)examination,slit-lamp microscopy,fundus examination and optical coherence tomography were per formed at each follow-up.The recurrence and treatment times of CNV were recorded.The patients were followed up for at least 12mo.RESULTS:The BCVA was increased in 29 eyes(82.9%)in group A and 30 eyes(93.75%)in group B;no increase or decrease was observed in 6(17.1%)and 2(6.25%)eyes in groups A and B,respectively.The BCVA(log MAR)values before treatment(0.67±0.48 and 0.71±0.56)were significantly higher than those 12mo after treatment(0.31±0.26 and 0.33±0.17)in groups A and B,respectively(P<0.05).The mean central macular thickness(CMT)values had significantly decreased from 346.49±65.99 and 360.10±82.31μm at baseline to 257.29±40.47 and 251.97±48.26μm in groups A and B,respectively,after 12mo of treatment.A total of 21 eyes in group A needed reinjection(60%;average number of injections,2.51±0.98);the corresponding values in group B were 6 eyes(18.75%;average number of injections,3.74±1.22).There were no adverse ocular and systemic complications during the treatment and follow-up.CONCLUSION:Intravitreal injection of conbercept with 1+PRN or 3+PRN improve the visual acuity,reduce macular edema and reduce the level of CMT in patients with PM-CNV.The 3+PRN regimen demonstrates a lower recurrence rate of CNV than the 1+PRN regimen,but requires more treatment.However,both treatment regimens demonstrate long-term safety and efficacy for the treatment of PM-CNV.展开更多
Myopic choroidal neovascularization(m CNV), one of the complications of pathological myopia, is also one of the leading causes of visual impairment worldwide. The socioeconomic impact of mC NV in Asian countries is pa...Myopic choroidal neovascularization(m CNV), one of the complications of pathological myopia, is also one of the leading causes of visual impairment worldwide. The socioeconomic impact of mC NV in Asian countries is particularly significant due to the rising incidence of pathological myopia. There have been major advances in the treatment of mC NV in the past few years. Previous treatment modalities, such as thermal laser photocoagulation and photodynamic therapy, aimed to prevent vision loss;however, newer modalities such as intravitreal anti-vascular endothelial growth factor(VEGF) agents have been shown to successfully restore vision in many patients. Challenges remain as long term safety and efficacy of anti-VEGF agents are unknown. This article aims to provide a review of the literature of the epidemiology, progression, clinical course and treatment modalities as well as areas of future developments related to myopic CNV.展开更多
Objective To develop a prognostic prediction model for early-stage triple-negative breast cancer(TNBC)using H&E-stained pathological images and to investigate its underlying biological interpretability.Methods A d...Objective To develop a prognostic prediction model for early-stage triple-negative breast cancer(TNBC)using H&E-stained pathological images and to investigate its underlying biological interpretability.Methods A deep learning model was trained on 340 WSIs and externally validated using 81 TCGA cases.Image-derived features extracted through convolutional neural networks were integrated with clinicopathological variables.Model performance was assessed using ROC curve analysis,and interpretability was evaluated by correlating image features with mRNA-seq data and characteristics of the immune microenvironment.Results The model achieved AUCs of 0.86 and 0.75 in the training and validation cohorts,respectively.Analysis using HoVer-Net indicated that lymphocyte abundance was associated with recurrence risk.Texture-related features showed significant correlations with immune cell infiltration and prognostic gene expression profiles.Conclusion This study demonstrates that deep learning can enable accurate prognostic prediction in early-stage TNBC,with interpretable image features that reflect the tumor immune microenvironment and gene expression profiles.展开更多
Whole Slide Imaging (WSI) technology, as a revolutionary digital technology in the field of pathology, is gradually changing the traditional clinical pathological diagnosis model. By converting traditional glass patho...Whole Slide Imaging (WSI) technology, as a revolutionary digital technology in the field of pathology, is gradually changing the traditional clinical pathological diagnosis model. By converting traditional glass pathological sections into complete digital images through high-resolution scanning, it provides a new method for pathological diagnosis. Based on this, this paper studies the application of WSI technology in clinical pathological diagnosis, elaborates on its application value, analyzes the current application status, and proposes corresponding application countermeasures, aiming to provide reference for the standardized and popularized development of this technology in clinical pathological diagnosis.展开更多
The respiratory-circulatory system, including organs such as the nose, pharynx, larynx, trachea, bronchi, and heart, is an organic community responsible for ventilation and gas exchange. The integrity of its anatomica...The respiratory-circulatory system, including organs such as the nose, pharynx, larynx, trachea, bronchi, and heart, is an organic community responsible for ventilation and gas exchange. The integrity of its anatomical structure directly affects the evolution of pathological processes, and the analysis of their correlation is a core entry point for clinical disease diagnosis, treatment, and mechanism research. Based on this, this paper mainly explores the correlation between the anatomical and pathological characteristics of the respiratory-circulatory system, aiming to provide anatomical and pathological theoretical support for clinical accurate diagnosis, targeted therapy, and prognosis evaluation.展开更多
Knee osteoarthritis(KOA)is a chronic degenerative disease.Monosodium iodoac-etate(MIA)induction is the most commonly used therapeutic effect evaluation and mechanism of action research model;we observed a lack of stan...Knee osteoarthritis(KOA)is a chronic degenerative disease.Monosodium iodoac-etate(MIA)induction is the most commonly used therapeutic effect evaluation and mechanism of action research model;we observed a lack of standardization and uni-formity in current model building methods,which led us to conduct this study.Background:The aim was to investigate the time-and dose-related changes in the behavioral and pathological characteristics in the MIA-induced KOA model rat.Methods:MIA(40,50,and 60 mg/mL)was injected into the left joint of male Sprague-Dawley rats.After 2 weeks,the changes in the KOA rat model were observed by be-havioral evaluation,imaging-level evaluation,and histological-level evaluation.The changes were also compared after 40-mg/mL MIA injection for 2 and 6 weeks.Results:MIA-induced bone surface defects,osteophyte hyperplasia around the artic-ular rim,increased subchondral bone density,thinning of the sparse trabecular bone,structural disorder,and local clustering were observed.The degree of injury gradually increased with the increase in MIA concentration.After 6 weeks,subchondral bone density and sparse trabecular bone increased in the KOA model.Conclusions:The severity of the model also increased significantly with the changes in dose and time.In dose-dependent experiments,this study revealed that 40 mg/mL was the optimal dose to induce significant pathological changes without causing undue discomfort or death in animals.This dose may induce pathological changes stably and is suitable for long-term observation.展开更多
BACKGROUND Inappropriate selection of patients with early gastric cancer(EGC)for endoscopic submucosal dissection(ESD)may lead to non-curative resection,necessitating additional gastrectomy.Conversely,inappropriate se...BACKGROUND Inappropriate selection of patients with early gastric cancer(EGC)for endoscopic submucosal dissection(ESD)may lead to non-curative resection,necessitating additional gastrectomy.Conversely,inappropriate selection for gastrectomy may result in overtreatment,adversely affecting patients’quality of life.Few have systematically evaluated the concordance between therapeutic indications under current Japanese guidelines and pathological criteria in EGC.To minimize noncurative resection risks while sparing unnecessary surgery for low-risk patients’,we specifically assess the suitability of Japanese guidelines in non-Japanese populations.This work aims to optimize clinical practice by refining endoscopic treatment criteria for adoption beyond Japan.AIM To evaluate EGC clinical decision accuracy by comparing therapeutic indication with postoperative pathological criteria and analyzing factors influencing discrepancies.METHODS A retrospective analysis was conducted on 796 EGC cases diagnosed at Peking University Third Hospital between January 2010 and December 2022.Cases were categorized into three groups:Same-estimated(preoperative therapeutic indication with postoperative pathological criteria matched),underestimated(preoperative ESD indication but postoperative surgical criteria),and overestimated(preoperative surgical indication but postoperative ESD criteria).The rate of discrepancy and associated risk factors were assessed.RESULTS The accuracy rates of preoperative evaluation for ESD and gastrectomy indications were 73.0%(321/430)and 76.0%(278/366),respectively.The overall discrepancy rate was 25.6%(204/796).Multivariate analysis identified tumor location in the upper-third stomach(odds ratio=2.158,95%confidence interval:1.373-3.390,P=0.001)was significantly associated with a higher likelihood of being underestimated and undifferentiated histologic type on preoperative biopsy(odds ratio=2.005,95%confidence interval:1.036-3.879,P=0.039)was more likely to be overestimated.Significant differences were observed in tumor diameter(P<0.001),depth of infiltration(P<0.001),ulcerative findings(P<0.001),and histologic type(P<0.001)between preoperative and postoperative evaluations.CONCLUSION The accuracy of preoperative EGC indications is 74.4%.Upper-third stomach and undifferentiated histology are primary discrepancy predictors.Upper-third tumors are prone to underestimation,while undifferentiated tumors are prone to overestimation.展开更多
Retinopathy of prematurity(ROP)is a vision-threatening disorder that leads to pathological growth of the retinal vasculature due to hypoxia.Here,we investigated the potential effects of alamandine,a novel heptapeptide...Retinopathy of prematurity(ROP)is a vision-threatening disorder that leads to pathological growth of the retinal vasculature due to hypoxia.Here,we investigated the potential effects of alamandine,a novel heptapeptide in the renin-angiotensin system(RAS),on hypoxia-induced retinal neovascularization and its underlying mechanisms.In vivo,the C57BL/6J mice with oxygen-induced retinopathy(OIR)were injected intravitreally with alamandine(1.0µmol/kg per eye).In vitro,human retinal microvascular endothelial cells(HRMECs)were utilized to investigate the effects of alamandine(10µg/mL)on proliferation,apoptosis,migration,and tubular formation under vascular endothelial growth factor(VEGF)stimulation.Single-cell RNA sequencing(scRNA-seq)matrix data from the Gene Expression Omnibus(GEO)database and RAS-related genes from the Molecular Signatures Database(MSigDB)were sourced for subsequent analyses.By integrating scRNA-seq data across multiple species,we identified that RAS-associated endothelial cell populations were highly related to retinal neovascularization.The liquid chromatography-tandem mass spectrometry(LC-MS/MS)analysis revealed a significant decrease in alamandine levels in both the serum and retina of OIR mice compared to those in the control group.Next,alamandine ameliorated hypoxia-induced retinal pathological neovascularization and physiologic revascularization in OIR mice.In vitro,alamandine effectively mitigated VEGF-induced proliferation,scratch wound healing,and tube formation of HRMECs primarily by inhibiting the hypoxia-inducible factor-1α(HIF-1α)/VEGF pathway.Further,coincubation with D-Pro7(Mas-related G protein-coupled receptor D(MrgD)antagonist)hindered the beneficial impacts of alamandine on hypoxia-induced pathological angiogenesis both in vivo and in vitro.Our findings suggested that alamandine could mitigate retinal neovascularization by targeting the MrgD-mediated HIF-1α/VEGF pathway,providing a potential therapeutic agent for OIR prevention and treatment.展开更多
Small intestinal villi are essential for nutrient absorption,and their impairment can lead to malabsorption.Small intestinal villous atrophy(VA)encompasses a heterogeneous group of disorders,including immune-mediated ...Small intestinal villi are essential for nutrient absorption,and their impairment can lead to malabsorption.Small intestinal villous atrophy(VA)encompasses a heterogeneous group of disorders,including immune-mediated conditions(e.g.,celiac disease,autoimmune enteropathy,inborn errors of immunity),lymphoproliferative disorders(e.g.,enteropathy-associated T-cell lymphoma),infectious causes(e.g.,tropical sprue,Whipple’s disease),iatrogenic factors(e.g.,Olmesartanassociated enteropathy,graft-vs-host disease),as well as inflammatory and idiopathic types.These disorders are often rare and challenging to distinguish due to overlapping clinical,serological,endoscopic,and histopathological features.Through a systematic literature search using keywords such as small intestinal VA,malabsorption,and specific enteropathies,this review provides a comprehensive overview of diagnostic clues for VA and malabsorption.We systematically summarize the pathological characteristics of each condition to assist pathologists and clinicians in accurately identifying the underlying etiologies.Current studies still have many limitations and lack broader and deeper investigations into these diseases.Therefore,future research should focus on the development of novel diagnostic tools,predictive models,therapeutic targets,and mechanistic molecular studies to refine both diagnosis and management strategies.展开更多
Neoadjuvant therapy(NAT)has become the standard treatment for patients with locally advanced breast cancer and stage II-III HER2-positive(HER2+)or triple-negative breast cancer(TNBC)1,2.It is essential to accurately m...Neoadjuvant therapy(NAT)has become the standard treatment for patients with locally advanced breast cancer and stage II-III HER2-positive(HER2+)or triple-negative breast cancer(TNBC)1,2.It is essential to accurately mark the primary breast tumor and positive axillary lymph nodes(ALNs)prior to NAT to ensure precise surgical excision,guide axillary downstaging,and guarantee reliable lesion retrieval for pathologic evaluation3.The false-negative rate of sentinel lymph node biopsy(SLNB)after NAT can be reduced to<10%by applying modalities,such as the identification of≥3 sentinel lymph nodes(SLNs)with dual-mapping techniques or removal of the marked lymph node with target axillary dissection(TAD)according to the ASCO,NCCN,and CBCS guidelines3-5.However,there is a lack of consensus regarding the optimal methods and materials for accurate marking6,7.Conventional techniques include clip placement,guidewire localization,and carbon or ink tattooing,whereas wireless technologies,such as MagseedR,radiofrequency identification tags,SAVI SCOUTR,and radioactive iodine-125(125I)seeds,have also been adopted.Traditional marking techniques have a localization failure rate of approximately 10%.In contrast,the use of 125I seeds(with a radiation dose of 0.1-0.3 mCi)has significantly improved localization accuracy8,9.Nevertheless,owing to radioactive properties,concerns have been raised regarding the potential impact of 125I seed marking on assessing the pathologic complete response(pCR)after NAT10.Moreover,whether the influence of 125I seed marking on pCR could lead to suboptimal adjuvant treatment decisions and potentially compromise long-term oncologic outcomes has not been established.To investigate the potential impact of 125I seed placement on the pCR rate and long-term outcomes in breast cancer patients receiving NAT,we conducted a retrospective cohort study utilizing propensity score matching(PSM).展开更多
Neuromyelitis optica spectrum disorder-related optic neuritis involves various cellular responses to inflammation and degeneration.In most patients,the primary mechanism underlying neuromyelitis optica spectrum disord...Neuromyelitis optica spectrum disorder-related optic neuritis involves various cellular responses to inflammation and degeneration.In most patients,the primary mechanism underlying neuromyelitis optica spectrum disorder-related optic neuritis is the interaction of aquaporin-4 antibodies with the aquaporin-4 protein present on astrocytes within posterior optic nerve.This binding subsequently initiates a cascade of events leading to secondary demyelination of the optic nerve,ultimately culminating in optic nerve degeneration.Earlier studies on this disorder primarily used systemic-induced animal models,which often require prior activation of a systemic immune response.This can result in primary demyelination of the optic nerve,complicating the interpretation of experimental results.Such methodologies hinder the ability to isolate immune responses triggered by specific antibodies.Additionally,the lack of a detailed profile of disease progression over time limits our capacity to identify potential intervention windows.Therefore,constructing a targeted optic neuritis animal model induced by specific antibodies and elucidate the disease progression arecrucial for exploring the mechanisms underlying neuromyelitis optica spectrum disorder-related optic neuritis.In this study,specific antibodies against aquaporin-4 were precisely injected into the retrobulbar optic nerve of mice to induce a targeted inflammatory response in the posterior optic nerve,resulting in a more representative mouse model of neuromyelitis optica spectrum disorder-related optic neuritis than current models.The progression of the disease was then dynamically observed from both histological and functional perspectives over the course of 1 month following the induction of inflammation.By the first week,astrocytes were damaged,as evidenced by the loss of aquaporin-4 and glial fibrillary acidic protein,the activation of microglia,and the upregulation of microglia-related cytokines,including tumor necrosis factor,interleukin-6,interleukin-1β,C-X-C motif ligand 10,and brain-derived neurotrophic factor.Starting from the second week,there were signs of optic nerve demyelination and significant damage to axonal fibers and retinal ganglion cell bodies.Visual-evoked potentials and dark adaptation threshold responses in electroretinogram both indicated dysfunction in the visual pathway and retina,while optical coherence tomography revealed thinning of the retinal nerve fiber layer in live mice.In summary,in this study we conducted a dynamic exploration of the occurrence and progression of neuromyelitis optica spectrum disorder-related optic neuritis triggered by specific antibodies.Our results show pathological changes at various stages and correlate histological and molecular alterations with in vivo structural and functional deterioration.The findings from this study lay an important foundation for further research on neuromyelitis optica spectrum disorder-related optic neuritis.展开更多
AIM:To explore the effect and mechanism of Lycium barbarum polysaccharide(LBP)inhibiting retinal neovascularization.METHODS:In vitro tests were performed on human retinal microvascular endothelial cells(HRECs)from thr...AIM:To explore the effect and mechanism of Lycium barbarum polysaccharide(LBP)inhibiting retinal neovascularization.METHODS:In vitro tests were performed on human retinal microvascular endothelial cells(HRECs)from three groups,including control group(normal oxygen),hypoxic group(hypoxia at 37℃,1%O_(2),5%CO_(2),and 94%N_(2)),and LBP group(hypoxic group with LBP 100μg/mL).In vivo experiments,C57 mice were divided into three groups:control group(normal rearing group),the oxygen-induced ischemic retinopathy(OIR)group,and the OIR with 50 mg/kg LBP group.Retinal neovascularization was observed by fluorescein angiography and quantified.Retinal thickness was evaluated by Hematoxylin and eosin(HE)stain.The expression of epidermal growth factor receptor(EGFR),phosphatidylinositol 3-kinase(PI3K),mammalian target of rapamycin(mTOR),phosphorylated mammalian target of rapamycin(p-mTOR),protein kinase B(AKT),phosphorylated protein kinase B(p-AKT),interleukin-1β(IL-1β),inducible nitric oxide synthase(iNOS),and tumor necrosis factor-α(TNF-α)in each group were analyzed by Western blot.IL-1βlevel in retina was analyzed using immunohistochemical staining.RESULTS:The increased area of neovascular clusters in OIR mice was significantly decreased by LBP.Retinal thickness of OIR mice was significantly thinner compared with normal oxygenated mice and was increased in LBP group.Compared with those in the hypoxic groups,Western blotting of HRECs and retinal tissues revealed that the expression of EGFR,PI3K,p-mTOR,p-AKT,IL-1β,iNOS,and TNF-αdecreased in the LBP group but was still greater than that in control group.Moreover,IL-1βwas reduced in retinal sections treated with LBP.In the scratch test,the cell migration of the hypoxic group was significantly greater than that of the control group,while LBP treatment attenuated this increase in migration.CONCLUSION:LBP reduces retinal neovascularization and inflammation in vivo and inhibits the migration of HRECs in vitro by regulating the EGFR/PI3K/Akt/mTOR signaling pathway.展开更多
BACKGROUND Esophageal squamous cell carcinoma is a major histological subtype of esophageal cancer.Many molecular genetic changes are associated with its occurrence.Raman spectroscopy has become a new method for the e...BACKGROUND Esophageal squamous cell carcinoma is a major histological subtype of esophageal cancer.Many molecular genetic changes are associated with its occurrence.Raman spectroscopy has become a new method for the early diagnosis of tumors because it can reflect the structures of substances and their changes at the molecular level.AIM To detect alterations in Raman spectral information across different stages of esophageal neoplasia.METHODS Different grades of esophageal lesions were collected,and a total of 360 groups of Raman spectrum data were collected.A 1D-transformer network model was proposed to handle the task of classifying the spectral data of esophageal squamous cell carcinoma.In addition,a deep learning model was applied to visualize the Raman spectral data and interpret their molecular characteristics.RESULTS A comparison among Raman spectral data with different pathological grades and a visual analysis revealed that the Raman peaks with significant differences were concentrated mainly at 1095 cm^(-1)(DNA,symmetric PO,and stretching vibration),1132 cm^(-1)(cytochrome c),1171 cm^(-1)(acetoacetate),1216 cm^(-1)(amide III),and 1315 cm^(-1)(glycerol).A comparison among the training results of different models revealed that the 1Dtransformer network performed best.A 93.30%accuracy value,a 96.65%specificity value,a 93.30%sensitivity value,and a 93.17%F1 score were achieved.CONCLUSION Raman spectroscopy revealed significantly different waveforms for the different stages of esophageal neoplasia.The combination of Raman spectroscopy and deep learning methods could significantly improve the accuracy of classification.展开更多
Objective:This study aims to develop a deep multiscale image learning system(DMILS)to differentiate malignant from benign thyroid follicular neoplasms on multiscale whole-slide images(WSIs)of intraoperative frozen pat...Objective:This study aims to develop a deep multiscale image learning system(DMILS)to differentiate malignant from benign thyroid follicular neoplasms on multiscale whole-slide images(WSIs)of intraoperative frozen pathological images.Methods:A total of 1,213 patients were divided into training and validation sets,an internal test set,a pooled external test set,and a pooled prospective test set at three centers.DMILS was constructed using a deep learningbased weakly supervised method based on multiscale WSIs at 10×,20×,and 40×magnifications.The performance of the DMILS was compared with that of a single magnification and validated in two pathologist-unidentified subsets.Results:The DMILS yielded good performance,with areas under the receiver operating characteristic curves(AUCs)of 0.848,0.857,0.810,and 0.787 in the training and validation sets,internal test set,pooled external test set,and pooled prospective test set,respectively.The AUC of the DMILS was higher than that of a single magnification,with 0.788 of 10×,0.824 of 20×,and 0.775 of 40×in the internal test set.Moreover,DMILS yielded satisfactory performance on the two pathologist-unidentified subsets.Furthermore,the most indicative region predicted by DMILS is the follicular epithelium.Conclusions:DMILS has good performance in differentiating thyroid follicular neoplasms on multiscale WSIs of intraoperative frozen pathological images.展开更多
AIM:To repor t the 24mo outcomes of vascular endothelial growth factor(VEGF)inhibitors for myopic choroidal neovascularization(mCNV)in routine clinical practice and simultaneously evaluated the real-world safety.METHO...AIM:To repor t the 24mo outcomes of vascular endothelial growth factor(VEGF)inhibitors for myopic choroidal neovascularization(mCNV)in routine clinical practice and simultaneously evaluated the real-world safety.METHODS:The patients who received intravitreal injections of VEGF inhibitors of either ranibizumab(0.5 mg)or conbercept(0.5 mg)for mCNV were analyzed from 1 January 2017 to 1 January 2022.The primary outcome variables were mean change in best-corrected visual acuity(BCVA)and central macular thickness(CMT)changes.The secondary outcome variables included IOP changes,the period of mCNV re-treatment,and ocular adverse events.RESULTS:Totally 83 patients aged 56.40±15.36y with axial length 29.67±2.09 mm were included.In visual acuity,the mean logMAR BCVA at baseline was 0.81±0.43.After the initial improvement at 1,3,and 6mo(P<0.05),from month 12 onwards,no statistical difference compared to baseline was found.The mean CMT from 1mo onwards had a statistically significant decrease compared with baseline CMT(P<0.05).The regression model showed better baseline BCVA and thicker baseline CMT,significantly associated with the final outcomes.In univariate analysis,choosing 3+pro re nata(PRN)as the initial injection treatment regimen was associated with better BCVA at 24mo[hazard ratio(HR)=-0.65,95%CI:-1.23,-0.07,P=0.048].However,the difference was not significant in multivariate analysis(HR=-0.59,95%CI:-1.21,0.03,P=0.089).Regarding mCNV recurrence,the mean period(P=0.725)and the proportion of mCNV reactivation(P=1.00)were similar between ranibizumab and conbercept.Kaplan-Meier plot also analyzed that the median time of re-injection was not significantly different among gender,drug,and initial injection treatment regimen.No systemic adverse events related to the therapy were observed.CONCLUSION:BCVA gains achieved by the end of our study maintain generally sustained at the 24-mo follow-up.The findings also indicate that ranibizumab and conbercept demonstrate comparable efficacy and safety profiles.Additionally,intravitreal anti-VEGF therapy using 1+PRN regimen,offers certain advantages in both efficacy and cost-effectiveness.展开更多
Erratum to:Current Medical Science https://doi.org/10.1007/s11596-025-00114-3In the originally published article(https://doi.org/10.1007/s11596-025-00114-3),the label of the vertical axis in Fig.2b was incorrect.Inste...Erratum to:Current Medical Science https://doi.org/10.1007/s11596-025-00114-3In the originally published article(https://doi.org/10.1007/s11596-025-00114-3),the label of the vertical axis in Fig.2b was incorrect.Instead of“24 h cell viability(%)”,it should be corrected to“Proliferation rate(%)”.The authors apologize for this error and state that this does not change the scientific conclusions of the article.展开更多
Introduction Choroidal neovascularization(CNV)associated with ocular inflammatory disease,also known as inflammatory CNV(iCNV),is a rare complication that can lead to severe vision loss in patients with infectious and...Introduction Choroidal neovascularization(CNV)associated with ocular inflammatory disease,also known as inflammatory CNV(iCNV),is a rare complication that can lead to severe vision loss in patients with infectious and noninfectious uveitis(1-3).After pathologic myopia,ocular inflammatory disease is a frequently implicated cause of CNV in patients younger than 50 years old(4).展开更多
AIM:To quantitatively assess central macular thickness(CMT),macular neovascularization(MNV)area,vascular tortuosity(VT),and vascular dispersion(VDisp)in neovascular age-related macular degeneration(nAMD),type 1 and ty...AIM:To quantitatively assess central macular thickness(CMT),macular neovascularization(MNV)area,vascular tortuosity(VT),and vascular dispersion(VDisp)in neovascular age-related macular degeneration(nAMD),type 1 and type 2 MNV,by means of optical coherence tomography(OCT)and OCT angiography(OCTA)techniques.METHODS:In this retrospective and observational case series,patients were classified into type 1 or type 2 MNV groups.A comprehensive panel of OCT and OCTA metrics was evaluated,including CMT,MNV area,VT,and VDisp.All subjects underwent a standardized intravitreal conbercept(IVC)regimen[3+pro re nata(PRN)]with a 12-month follow-up.MNV area was obtained by manual measurements with OCTA software,and VT and VDisp were calculated by automated analysis with Image J software.RESULTS:A total of 101 participants were included,with 51 patients in the type 1 MNV group(mean age 67.32±9.12y)and 50 patients in the type 2 MNV group(mean age 64.74±5.21y).The mean number of IVC injections was 3.98±1.53 for type 1 MNV and 3.73±0.81 for type 2 MNV.Both subtypes exhibited significant improvements in visual acuity,accompanied by marked reductions in CMT and MNV area(P<0.05)at 12mo after treatment.In type 2 MNV,VT significantly decreased(P<0.05),whereas no significant change was observed in VT for type 1 MNV.VDisp did not significantly changed in either sybtypes.Moreover,in type 1 MNV,final best-corrected visual acuity(BCVA)using logMAR correlated positively with both pre-and post-treatment CMT,while in type 2 MNV,a significant positive correlation was found between the number of injections and final CMT.CONCLUSION:This study shows that conbercept treatment significantly improves visual acuity and macular structure in both type 1 and type 2 MNV with reductions in CMT and MNV area.The significant reduction in VT in type 2 MNV suggests its potential as a biomarker for disease activity.The findings imply the quantitative assessment useful for the stratification,prognostication,and personalized management of MNV in nAMD.展开更多
AIM:To investigate the choroidal vascular index(CVI)and the choroidal structural changes beyond the subfoveal area(analyzed across a 20 mm×24 mm scanning area)in eyes with chronic central serous chorioretinopathy...AIM:To investigate the choroidal vascular index(CVI)and the choroidal structural changes beyond the subfoveal area(analyzed across a 20 mm×24 mm scanning area)in eyes with chronic central serous chorioretinopathy(cCSC)eyes with macular neovascularization(MNV)using ultra-widefield swept-source optical coherence tomography angiography(UWF SS-OCTA).METHODS:This retrospective comparative study included 46 cCSC with MNV eyes(With MNV group),52 cCSC without MNV eyes(Without MNV group),and 40 age-matched healthy controls.UWF SS-OCTA imaging with a 20 mm×24 mm protocol was used to quantify CVI across 9 subfields(superotemporal,superior,superonasal,temporal,central,nasal,inferotemporal,inferior,and inferonasal).The CVI was compared among the groups.RESULTS:With MNV group demonstrated significantly older mean age than Without MNV group(56.2±6.1 vs 47.5±8.6y,P<0.001).The CVI was significantly lower in the With MNV group than in the Without MNV group,except in the superotemporal,superior,and temporal regions(all P<0.05).Notably,despite MNV-associated CVI reductions,the With MNV group maintained a higher CVI than the control group in all 5 subfields(superior,temporal,central,inferior,and inferonasal;all P<0.05).In the central region,CONCLUSION:CVI decreases,and choroidal structural changes extend beyond the subfoveal area in cCSC with MNV eyes,providing with an imaging evidence for the important role of choroidal ischemia in the pathogenesis of MNV in cCSC.展开更多
Objective:To explore clinicopathological predictors of adverse pathological changes(APCs)(upgrading,upstaging,and positive surgical margin[PSM])after robot-assisted radical prostatectomy(RARP)in clinical tumor stage 2...Objective:To explore clinicopathological predictors of adverse pathological changes(APCs)(upgrading,upstaging,and positive surgical margin[PSM])after robot-assisted radical prostatectomy(RARP)in clinical tumor stage 2c(cT2c)prostate cancer(PCa)patients.Methods:From January 2018 to December 2022,cT2cN0M0 PCa patients who underwent prostate biopsies and subsequent RARP at the Peking University First Hospital with an interval between biopsy and RARP of ≤90 days were included.Univariable and stepwise multivariable logistic regression analyses were performed to identify independent risk factors associated with APCs.Nomograms were constructed based on these predictive models.The performance of the nomograms was evaluated by receiver operating characteristic curves,decision curve analyses,and calibration plots.Results:A total of 423 eligible cT2cN0M0 PCa patients were included.The rates of upgrading,upstaging,and PSM in our cohortwere 33%,51%,and 35%,respectively.The stepwise multivariate logistic analysis suggested that PSA density and the percentage of positive cores in systematic biopsy were significantly associated with the occurrence of APCs.The score of the Prostate Imaging Reporting and Data System,PSA density,and the International Society of Urological Pathology grade group(IGG)of needle-biopsy specimens(or clinical IGG[cIGG])were significantly associated with upgrading.The PSA density,percentage of positive cores in systematic biopsy,and largest tumor percentage in all cores of each patient(LTP)were significantly associated with upstaging.The PSA density and LTP were significantly associatedwith the PSM.Based on these results,four nomogramswere developed.Receiver operating characteristic curves,decision curve analyses,and calibration plots implied that the nomograms exhibited excellent accuracy.Conclusion:The predictive models we developed could help to identify high-risk PCa early,and optimize clinical decisions of cT2cN0M0 PCa patients.展开更多
文摘AIM:To observe the long-term clinical efficacy of intravitreal injections of conbercept,a novel vascular growth factor inhibitor,for the treatment of pathological myopia choroidal neovascularization(PM-CNV).METHODS:A total of 67 eyes(from 67 patients;mean age,54.90±12.7y)with PM-CNV were retrospectively researched.Based on the different schemes used for the administration of the drug,the patients were divided into two groups:group A(n=35;average age,53.31±13.6y;average diopter,9.25±1.72 D),which received only one injection of pro re nata(PRN;1+PRN regimen),and group B(n=32;average age,56.49±11.8y;average diopter,9.63±2.24 D),which received one injection per month for 3mo(3+PRN regimen).Best-corrected visual acuity(BCVA)analysis,intraocular pressure(IOP)examination,slit-lamp microscopy,fundus examination and optical coherence tomography were per formed at each follow-up.The recurrence and treatment times of CNV were recorded.The patients were followed up for at least 12mo.RESULTS:The BCVA was increased in 29 eyes(82.9%)in group A and 30 eyes(93.75%)in group B;no increase or decrease was observed in 6(17.1%)and 2(6.25%)eyes in groups A and B,respectively.The BCVA(log MAR)values before treatment(0.67±0.48 and 0.71±0.56)were significantly higher than those 12mo after treatment(0.31±0.26 and 0.33±0.17)in groups A and B,respectively(P<0.05).The mean central macular thickness(CMT)values had significantly decreased from 346.49±65.99 and 360.10±82.31μm at baseline to 257.29±40.47 and 251.97±48.26μm in groups A and B,respectively,after 12mo of treatment.A total of 21 eyes in group A needed reinjection(60%;average number of injections,2.51±0.98);the corresponding values in group B were 6 eyes(18.75%;average number of injections,3.74±1.22).There were no adverse ocular and systemic complications during the treatment and follow-up.CONCLUSION:Intravitreal injection of conbercept with 1+PRN or 3+PRN improve the visual acuity,reduce macular edema and reduce the level of CMT in patients with PM-CNV.The 3+PRN regimen demonstrates a lower recurrence rate of CNV than the 1+PRN regimen,but requires more treatment.However,both treatment regimens demonstrate long-term safety and efficacy for the treatment of PM-CNV.
文摘Myopic choroidal neovascularization(m CNV), one of the complications of pathological myopia, is also one of the leading causes of visual impairment worldwide. The socioeconomic impact of mC NV in Asian countries is particularly significant due to the rising incidence of pathological myopia. There have been major advances in the treatment of mC NV in the past few years. Previous treatment modalities, such as thermal laser photocoagulation and photodynamic therapy, aimed to prevent vision loss;however, newer modalities such as intravitreal anti-vascular endothelial growth factor(VEGF) agents have been shown to successfully restore vision in many patients. Challenges remain as long term safety and efficacy of anti-VEGF agents are unknown. This article aims to provide a review of the literature of the epidemiology, progression, clinical course and treatment modalities as well as areas of future developments related to myopic CNV.
基金Supported by Capital’s Funds for Health Improvement and Research(CFH2024-1-4021)。
文摘Objective To develop a prognostic prediction model for early-stage triple-negative breast cancer(TNBC)using H&E-stained pathological images and to investigate its underlying biological interpretability.Methods A deep learning model was trained on 340 WSIs and externally validated using 81 TCGA cases.Image-derived features extracted through convolutional neural networks were integrated with clinicopathological variables.Model performance was assessed using ROC curve analysis,and interpretability was evaluated by correlating image features with mRNA-seq data and characteristics of the immune microenvironment.Results The model achieved AUCs of 0.86 and 0.75 in the training and validation cohorts,respectively.Analysis using HoVer-Net indicated that lymphocyte abundance was associated with recurrence risk.Texture-related features showed significant correlations with immune cell infiltration and prognostic gene expression profiles.Conclusion This study demonstrates that deep learning can enable accurate prognostic prediction in early-stage TNBC,with interpretable image features that reflect the tumor immune microenvironment and gene expression profiles.
文摘Whole Slide Imaging (WSI) technology, as a revolutionary digital technology in the field of pathology, is gradually changing the traditional clinical pathological diagnosis model. By converting traditional glass pathological sections into complete digital images through high-resolution scanning, it provides a new method for pathological diagnosis. Based on this, this paper studies the application of WSI technology in clinical pathological diagnosis, elaborates on its application value, analyzes the current application status, and proposes corresponding application countermeasures, aiming to provide reference for the standardized and popularized development of this technology in clinical pathological diagnosis.
文摘The respiratory-circulatory system, including organs such as the nose, pharynx, larynx, trachea, bronchi, and heart, is an organic community responsible for ventilation and gas exchange. The integrity of its anatomical structure directly affects the evolution of pathological processes, and the analysis of their correlation is a core entry point for clinical disease diagnosis, treatment, and mechanism research. Based on this, this paper mainly explores the correlation between the anatomical and pathological characteristics of the respiratory-circulatory system, aiming to provide anatomical and pathological theoretical support for clinical accurate diagnosis, targeted therapy, and prognosis evaluation.
基金Construction Project of High-Level Traditional Chinese Medicine Key Discipline of National Administration of Traditional Chinese Medicine,Grant/Award Number:zyyzdxk-2023022Key Team of Scientific and Technological Innovation Talents of Shanxi Province with Integrated Traditional Chinese and Western Medicine for Preventing and Treating Rheumatological Diseases,Grant/Award Number:202204051002033+4 种基金Traditional Chinese Medicine+Stem Cell Innovation Project,Grant/Award Number:2024KJZY0062023 Shanxi Graduate Research Practice Project,Grant/Award Number:2023KY6762023 Graduate Innovation and Entrepreneurship Project of Shanxi University of Traditional Chinese Medicine,Grant/Award Number:2023CX023 and 2023CX027Science and Technology Innovation Project for University in Shanxi Province,Grant/Award Number:2022L358Key Laboratory of Rheumatological and Immunological Diseases Treated by Integrated Chinese and Western Medicine,Grant/Award Number:zyyyjs2024021。
文摘Knee osteoarthritis(KOA)is a chronic degenerative disease.Monosodium iodoac-etate(MIA)induction is the most commonly used therapeutic effect evaluation and mechanism of action research model;we observed a lack of standardization and uni-formity in current model building methods,which led us to conduct this study.Background:The aim was to investigate the time-and dose-related changes in the behavioral and pathological characteristics in the MIA-induced KOA model rat.Methods:MIA(40,50,and 60 mg/mL)was injected into the left joint of male Sprague-Dawley rats.After 2 weeks,the changes in the KOA rat model were observed by be-havioral evaluation,imaging-level evaluation,and histological-level evaluation.The changes were also compared after 40-mg/mL MIA injection for 2 and 6 weeks.Results:MIA-induced bone surface defects,osteophyte hyperplasia around the artic-ular rim,increased subchondral bone density,thinning of the sparse trabecular bone,structural disorder,and local clustering were observed.The degree of injury gradually increased with the increase in MIA concentration.After 6 weeks,subchondral bone density and sparse trabecular bone increased in the KOA model.Conclusions:The severity of the model also increased significantly with the changes in dose and time.In dose-dependent experiments,this study revealed that 40 mg/mL was the optimal dose to induce significant pathological changes without causing undue discomfort or death in animals.This dose may induce pathological changes stably and is suitable for long-term observation.
基金Supported by China Health&Medical Development Foundation,No.M2021551.
文摘BACKGROUND Inappropriate selection of patients with early gastric cancer(EGC)for endoscopic submucosal dissection(ESD)may lead to non-curative resection,necessitating additional gastrectomy.Conversely,inappropriate selection for gastrectomy may result in overtreatment,adversely affecting patients’quality of life.Few have systematically evaluated the concordance between therapeutic indications under current Japanese guidelines and pathological criteria in EGC.To minimize noncurative resection risks while sparing unnecessary surgery for low-risk patients’,we specifically assess the suitability of Japanese guidelines in non-Japanese populations.This work aims to optimize clinical practice by refining endoscopic treatment criteria for adoption beyond Japan.AIM To evaluate EGC clinical decision accuracy by comparing therapeutic indication with postoperative pathological criteria and analyzing factors influencing discrepancies.METHODS A retrospective analysis was conducted on 796 EGC cases diagnosed at Peking University Third Hospital between January 2010 and December 2022.Cases were categorized into three groups:Same-estimated(preoperative therapeutic indication with postoperative pathological criteria matched),underestimated(preoperative ESD indication but postoperative surgical criteria),and overestimated(preoperative surgical indication but postoperative ESD criteria).The rate of discrepancy and associated risk factors were assessed.RESULTS The accuracy rates of preoperative evaluation for ESD and gastrectomy indications were 73.0%(321/430)and 76.0%(278/366),respectively.The overall discrepancy rate was 25.6%(204/796).Multivariate analysis identified tumor location in the upper-third stomach(odds ratio=2.158,95%confidence interval:1.373-3.390,P=0.001)was significantly associated with a higher likelihood of being underestimated and undifferentiated histologic type on preoperative biopsy(odds ratio=2.005,95%confidence interval:1.036-3.879,P=0.039)was more likely to be overestimated.Significant differences were observed in tumor diameter(P<0.001),depth of infiltration(P<0.001),ulcerative findings(P<0.001),and histologic type(P<0.001)between preoperative and postoperative evaluations.CONCLUSION The accuracy of preoperative EGC indications is 74.4%.Upper-third stomach and undifferentiated histology are primary discrepancy predictors.Upper-third tumors are prone to underestimation,while undifferentiated tumors are prone to overestimation.
基金supported by the National Natural Science Foundation of China(Nos.82200379 and 82300309)the Shanghai Sailing Program(No.22YF1443100)+1 种基金the Academy Talent Special Fund of The First Affiliated Hospital of Nanjing Medical University(Nos.YNRCQN0312 and MXJL202208)the Jiangsu Funding Program for Excellent Postdoctoral Talent(No.2023ZB592),China.
文摘Retinopathy of prematurity(ROP)is a vision-threatening disorder that leads to pathological growth of the retinal vasculature due to hypoxia.Here,we investigated the potential effects of alamandine,a novel heptapeptide in the renin-angiotensin system(RAS),on hypoxia-induced retinal neovascularization and its underlying mechanisms.In vivo,the C57BL/6J mice with oxygen-induced retinopathy(OIR)were injected intravitreally with alamandine(1.0µmol/kg per eye).In vitro,human retinal microvascular endothelial cells(HRMECs)were utilized to investigate the effects of alamandine(10µg/mL)on proliferation,apoptosis,migration,and tubular formation under vascular endothelial growth factor(VEGF)stimulation.Single-cell RNA sequencing(scRNA-seq)matrix data from the Gene Expression Omnibus(GEO)database and RAS-related genes from the Molecular Signatures Database(MSigDB)were sourced for subsequent analyses.By integrating scRNA-seq data across multiple species,we identified that RAS-associated endothelial cell populations were highly related to retinal neovascularization.The liquid chromatography-tandem mass spectrometry(LC-MS/MS)analysis revealed a significant decrease in alamandine levels in both the serum and retina of OIR mice compared to those in the control group.Next,alamandine ameliorated hypoxia-induced retinal pathological neovascularization and physiologic revascularization in OIR mice.In vitro,alamandine effectively mitigated VEGF-induced proliferation,scratch wound healing,and tube formation of HRMECs primarily by inhibiting the hypoxia-inducible factor-1α(HIF-1α)/VEGF pathway.Further,coincubation with D-Pro7(Mas-related G protein-coupled receptor D(MrgD)antagonist)hindered the beneficial impacts of alamandine on hypoxia-induced pathological angiogenesis both in vivo and in vitro.Our findings suggested that alamandine could mitigate retinal neovascularization by targeting the MrgD-mediated HIF-1α/VEGF pathway,providing a potential therapeutic agent for OIR prevention and treatment.
基金Supported by National High-Level Hospital Clinical Research Funding,No.2022-PUMCH-B-022,and No.2022-PUMCH-D-002CAMS Innovation Fund for Medical Sciences,No.CIFMS 2021-1-I2M-003Undergraduate Innovation Program,No.2024dcxm025.
文摘Small intestinal villi are essential for nutrient absorption,and their impairment can lead to malabsorption.Small intestinal villous atrophy(VA)encompasses a heterogeneous group of disorders,including immune-mediated conditions(e.g.,celiac disease,autoimmune enteropathy,inborn errors of immunity),lymphoproliferative disorders(e.g.,enteropathy-associated T-cell lymphoma),infectious causes(e.g.,tropical sprue,Whipple’s disease),iatrogenic factors(e.g.,Olmesartanassociated enteropathy,graft-vs-host disease),as well as inflammatory and idiopathic types.These disorders are often rare and challenging to distinguish due to overlapping clinical,serological,endoscopic,and histopathological features.Through a systematic literature search using keywords such as small intestinal VA,malabsorption,and specific enteropathies,this review provides a comprehensive overview of diagnostic clues for VA and malabsorption.We systematically summarize the pathological characteristics of each condition to assist pathologists and clinicians in accurately identifying the underlying etiologies.Current studies still have many limitations and lack broader and deeper investigations into these diseases.Therefore,future research should focus on the development of novel diagnostic tools,predictive models,therapeutic targets,and mechanistic molecular studies to refine both diagnosis and management strategies.
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.82573747,82172873,W2421095,and 82503888)National Science and Technology Major Project(Grant No.2025ZD0543900)+2 种基金Natural Science Foundation of Shandong Province(Grant Nos.ZR2024LMB011 and ZR2024QH058)Taishan Scholars Program of Shandong Province(Grant No.tsqn202211337)Collaborative Academic Innovation Project of Shandong Cancer Hospital(Grant No.GF003).
文摘Neoadjuvant therapy(NAT)has become the standard treatment for patients with locally advanced breast cancer and stage II-III HER2-positive(HER2+)or triple-negative breast cancer(TNBC)1,2.It is essential to accurately mark the primary breast tumor and positive axillary lymph nodes(ALNs)prior to NAT to ensure precise surgical excision,guide axillary downstaging,and guarantee reliable lesion retrieval for pathologic evaluation3.The false-negative rate of sentinel lymph node biopsy(SLNB)after NAT can be reduced to<10%by applying modalities,such as the identification of≥3 sentinel lymph nodes(SLNs)with dual-mapping techniques or removal of the marked lymph node with target axillary dissection(TAD)according to the ASCO,NCCN,and CBCS guidelines3-5.However,there is a lack of consensus regarding the optimal methods and materials for accurate marking6,7.Conventional techniques include clip placement,guidewire localization,and carbon or ink tattooing,whereas wireless technologies,such as MagseedR,radiofrequency identification tags,SAVI SCOUTR,and radioactive iodine-125(125I)seeds,have also been adopted.Traditional marking techniques have a localization failure rate of approximately 10%.In contrast,the use of 125I seeds(with a radiation dose of 0.1-0.3 mCi)has significantly improved localization accuracy8,9.Nevertheless,owing to radioactive properties,concerns have been raised regarding the potential impact of 125I seed marking on assessing the pathologic complete response(pCR)after NAT10.Moreover,whether the influence of 125I seed marking on pCR could lead to suboptimal adjuvant treatment decisions and potentially compromise long-term oncologic outcomes has not been established.To investigate the potential impact of 125I seed placement on the pCR rate and long-term outcomes in breast cancer patients receiving NAT,we conducted a retrospective cohort study utilizing propensity score matching(PSM).
基金The study was partially supported by the General Research Fund(GRF)from the Research Grants Council(RGC)of the Hong Kong Special Administrative Region,China,No.15103522(to ST)the Internal Research Grant from the Hong Kong Polytechnic University 2021-23,No.P0035512(to ST)and P0035375(to HHLC)+1 种基金the Innovation and Technology Commission of the Hong Kong Special Administrative Region(ITC InnoHK CEVR Project)The Hong Kong Polytechnics University Research Center for Sharp Vision,No.P0039595.
文摘Neuromyelitis optica spectrum disorder-related optic neuritis involves various cellular responses to inflammation and degeneration.In most patients,the primary mechanism underlying neuromyelitis optica spectrum disorder-related optic neuritis is the interaction of aquaporin-4 antibodies with the aquaporin-4 protein present on astrocytes within posterior optic nerve.This binding subsequently initiates a cascade of events leading to secondary demyelination of the optic nerve,ultimately culminating in optic nerve degeneration.Earlier studies on this disorder primarily used systemic-induced animal models,which often require prior activation of a systemic immune response.This can result in primary demyelination of the optic nerve,complicating the interpretation of experimental results.Such methodologies hinder the ability to isolate immune responses triggered by specific antibodies.Additionally,the lack of a detailed profile of disease progression over time limits our capacity to identify potential intervention windows.Therefore,constructing a targeted optic neuritis animal model induced by specific antibodies and elucidate the disease progression arecrucial for exploring the mechanisms underlying neuromyelitis optica spectrum disorder-related optic neuritis.In this study,specific antibodies against aquaporin-4 were precisely injected into the retrobulbar optic nerve of mice to induce a targeted inflammatory response in the posterior optic nerve,resulting in a more representative mouse model of neuromyelitis optica spectrum disorder-related optic neuritis than current models.The progression of the disease was then dynamically observed from both histological and functional perspectives over the course of 1 month following the induction of inflammation.By the first week,astrocytes were damaged,as evidenced by the loss of aquaporin-4 and glial fibrillary acidic protein,the activation of microglia,and the upregulation of microglia-related cytokines,including tumor necrosis factor,interleukin-6,interleukin-1β,C-X-C motif ligand 10,and brain-derived neurotrophic factor.Starting from the second week,there were signs of optic nerve demyelination and significant damage to axonal fibers and retinal ganglion cell bodies.Visual-evoked potentials and dark adaptation threshold responses in electroretinogram both indicated dysfunction in the visual pathway and retina,while optical coherence tomography revealed thinning of the retinal nerve fiber layer in live mice.In summary,in this study we conducted a dynamic exploration of the occurrence and progression of neuromyelitis optica spectrum disorder-related optic neuritis triggered by specific antibodies.Our results show pathological changes at various stages and correlate histological and molecular alterations with in vivo structural and functional deterioration.The findings from this study lay an important foundation for further research on neuromyelitis optica spectrum disorder-related optic neuritis.
基金Supported by the Tianjin Health Research Project(No.ZC20069No.TJWJ2022MS040)+1 种基金the Foundation of the Committee of Integrated Traditional Chinese and Western Medicine(No.2021011)the Science and Technology Foundation of Tianjin Eye Hospital(No.YKYB1901).
文摘AIM:To explore the effect and mechanism of Lycium barbarum polysaccharide(LBP)inhibiting retinal neovascularization.METHODS:In vitro tests were performed on human retinal microvascular endothelial cells(HRECs)from three groups,including control group(normal oxygen),hypoxic group(hypoxia at 37℃,1%O_(2),5%CO_(2),and 94%N_(2)),and LBP group(hypoxic group with LBP 100μg/mL).In vivo experiments,C57 mice were divided into three groups:control group(normal rearing group),the oxygen-induced ischemic retinopathy(OIR)group,and the OIR with 50 mg/kg LBP group.Retinal neovascularization was observed by fluorescein angiography and quantified.Retinal thickness was evaluated by Hematoxylin and eosin(HE)stain.The expression of epidermal growth factor receptor(EGFR),phosphatidylinositol 3-kinase(PI3K),mammalian target of rapamycin(mTOR),phosphorylated mammalian target of rapamycin(p-mTOR),protein kinase B(AKT),phosphorylated protein kinase B(p-AKT),interleukin-1β(IL-1β),inducible nitric oxide synthase(iNOS),and tumor necrosis factor-α(TNF-α)in each group were analyzed by Western blot.IL-1βlevel in retina was analyzed using immunohistochemical staining.RESULTS:The increased area of neovascular clusters in OIR mice was significantly decreased by LBP.Retinal thickness of OIR mice was significantly thinner compared with normal oxygenated mice and was increased in LBP group.Compared with those in the hypoxic groups,Western blotting of HRECs and retinal tissues revealed that the expression of EGFR,PI3K,p-mTOR,p-AKT,IL-1β,iNOS,and TNF-αdecreased in the LBP group but was still greater than that in control group.Moreover,IL-1βwas reduced in retinal sections treated with LBP.In the scratch test,the cell migration of the hypoxic group was significantly greater than that of the control group,while LBP treatment attenuated this increase in migration.CONCLUSION:LBP reduces retinal neovascularization and inflammation in vivo and inhibits the migration of HRECs in vitro by regulating the EGFR/PI3K/Akt/mTOR signaling pathway.
基金Supported by Beijing Hospitals Authority Youth Programme,No.QML20200505.
文摘BACKGROUND Esophageal squamous cell carcinoma is a major histological subtype of esophageal cancer.Many molecular genetic changes are associated with its occurrence.Raman spectroscopy has become a new method for the early diagnosis of tumors because it can reflect the structures of substances and their changes at the molecular level.AIM To detect alterations in Raman spectral information across different stages of esophageal neoplasia.METHODS Different grades of esophageal lesions were collected,and a total of 360 groups of Raman spectrum data were collected.A 1D-transformer network model was proposed to handle the task of classifying the spectral data of esophageal squamous cell carcinoma.In addition,a deep learning model was applied to visualize the Raman spectral data and interpret their molecular characteristics.RESULTS A comparison among Raman spectral data with different pathological grades and a visual analysis revealed that the Raman peaks with significant differences were concentrated mainly at 1095 cm^(-1)(DNA,symmetric PO,and stretching vibration),1132 cm^(-1)(cytochrome c),1171 cm^(-1)(acetoacetate),1216 cm^(-1)(amide III),and 1315 cm^(-1)(glycerol).A comparison among the training results of different models revealed that the 1Dtransformer network performed best.A 93.30%accuracy value,a 96.65%specificity value,a 93.30%sensitivity value,and a 93.17%F1 score were achieved.CONCLUSION Raman spectroscopy revealed significantly different waveforms for the different stages of esophageal neoplasia.The combination of Raman spectroscopy and deep learning methods could significantly improve the accuracy of classification.
基金supported by the Taishan Scholar Project(No.ts20190991,tsqn202211378)the Key R&D Project of Shandong Province(No.2022CXPT023)the General Program of National Natural Science Foundation of China(No.82371933)。
文摘Objective:This study aims to develop a deep multiscale image learning system(DMILS)to differentiate malignant from benign thyroid follicular neoplasms on multiscale whole-slide images(WSIs)of intraoperative frozen pathological images.Methods:A total of 1,213 patients were divided into training and validation sets,an internal test set,a pooled external test set,and a pooled prospective test set at three centers.DMILS was constructed using a deep learningbased weakly supervised method based on multiscale WSIs at 10×,20×,and 40×magnifications.The performance of the DMILS was compared with that of a single magnification and validated in two pathologist-unidentified subsets.Results:The DMILS yielded good performance,with areas under the receiver operating characteristic curves(AUCs)of 0.848,0.857,0.810,and 0.787 in the training and validation sets,internal test set,pooled external test set,and pooled prospective test set,respectively.The AUC of the DMILS was higher than that of a single magnification,with 0.788 of 10×,0.824 of 20×,and 0.775 of 40×in the internal test set.Moreover,DMILS yielded satisfactory performance on the two pathologist-unidentified subsets.Furthermore,the most indicative region predicted by DMILS is the follicular epithelium.Conclusions:DMILS has good performance in differentiating thyroid follicular neoplasms on multiscale WSIs of intraoperative frozen pathological images.
基金Supported by Tianjin Key Medical Discipline(Specialty)Construction Project(No.TJYXZDXK-037A).
文摘AIM:To repor t the 24mo outcomes of vascular endothelial growth factor(VEGF)inhibitors for myopic choroidal neovascularization(mCNV)in routine clinical practice and simultaneously evaluated the real-world safety.METHODS:The patients who received intravitreal injections of VEGF inhibitors of either ranibizumab(0.5 mg)or conbercept(0.5 mg)for mCNV were analyzed from 1 January 2017 to 1 January 2022.The primary outcome variables were mean change in best-corrected visual acuity(BCVA)and central macular thickness(CMT)changes.The secondary outcome variables included IOP changes,the period of mCNV re-treatment,and ocular adverse events.RESULTS:Totally 83 patients aged 56.40±15.36y with axial length 29.67±2.09 mm were included.In visual acuity,the mean logMAR BCVA at baseline was 0.81±0.43.After the initial improvement at 1,3,and 6mo(P<0.05),from month 12 onwards,no statistical difference compared to baseline was found.The mean CMT from 1mo onwards had a statistically significant decrease compared with baseline CMT(P<0.05).The regression model showed better baseline BCVA and thicker baseline CMT,significantly associated with the final outcomes.In univariate analysis,choosing 3+pro re nata(PRN)as the initial injection treatment regimen was associated with better BCVA at 24mo[hazard ratio(HR)=-0.65,95%CI:-1.23,-0.07,P=0.048].However,the difference was not significant in multivariate analysis(HR=-0.59,95%CI:-1.21,0.03,P=0.089).Regarding mCNV recurrence,the mean period(P=0.725)and the proportion of mCNV reactivation(P=1.00)were similar between ranibizumab and conbercept.Kaplan-Meier plot also analyzed that the median time of re-injection was not significantly different among gender,drug,and initial injection treatment regimen.No systemic adverse events related to the therapy were observed.CONCLUSION:BCVA gains achieved by the end of our study maintain generally sustained at the 24-mo follow-up.The findings also indicate that ranibizumab and conbercept demonstrate comparable efficacy and safety profiles.Additionally,intravitreal anti-VEGF therapy using 1+PRN regimen,offers certain advantages in both efficacy and cost-effectiveness.
文摘Erratum to:Current Medical Science https://doi.org/10.1007/s11596-025-00114-3In the originally published article(https://doi.org/10.1007/s11596-025-00114-3),the label of the vertical axis in Fig.2b was incorrect.Instead of“24 h cell viability(%)”,it should be corrected to“Proliferation rate(%)”.The authors apologize for this error and state that this does not change the scientific conclusions of the article.
文摘Introduction Choroidal neovascularization(CNV)associated with ocular inflammatory disease,also known as inflammatory CNV(iCNV),is a rare complication that can lead to severe vision loss in patients with infectious and noninfectious uveitis(1-3).After pathologic myopia,ocular inflammatory disease is a frequently implicated cause of CNV in patients younger than 50 years old(4).
基金Supported by Natural Science Foundation of Shandong Province(No.ZR2023MH363)Bethune Langmu Young Scholars Research Fund Project(No.BJ-LM2021007J).
文摘AIM:To quantitatively assess central macular thickness(CMT),macular neovascularization(MNV)area,vascular tortuosity(VT),and vascular dispersion(VDisp)in neovascular age-related macular degeneration(nAMD),type 1 and type 2 MNV,by means of optical coherence tomography(OCT)and OCT angiography(OCTA)techniques.METHODS:In this retrospective and observational case series,patients were classified into type 1 or type 2 MNV groups.A comprehensive panel of OCT and OCTA metrics was evaluated,including CMT,MNV area,VT,and VDisp.All subjects underwent a standardized intravitreal conbercept(IVC)regimen[3+pro re nata(PRN)]with a 12-month follow-up.MNV area was obtained by manual measurements with OCTA software,and VT and VDisp were calculated by automated analysis with Image J software.RESULTS:A total of 101 participants were included,with 51 patients in the type 1 MNV group(mean age 67.32±9.12y)and 50 patients in the type 2 MNV group(mean age 64.74±5.21y).The mean number of IVC injections was 3.98±1.53 for type 1 MNV and 3.73±0.81 for type 2 MNV.Both subtypes exhibited significant improvements in visual acuity,accompanied by marked reductions in CMT and MNV area(P<0.05)at 12mo after treatment.In type 2 MNV,VT significantly decreased(P<0.05),whereas no significant change was observed in VT for type 1 MNV.VDisp did not significantly changed in either sybtypes.Moreover,in type 1 MNV,final best-corrected visual acuity(BCVA)using logMAR correlated positively with both pre-and post-treatment CMT,while in type 2 MNV,a significant positive correlation was found between the number of injections and final CMT.CONCLUSION:This study shows that conbercept treatment significantly improves visual acuity and macular structure in both type 1 and type 2 MNV with reductions in CMT and MNV area.The significant reduction in VT in type 2 MNV suggests its potential as a biomarker for disease activity.The findings imply the quantitative assessment useful for the stratification,prognostication,and personalized management of MNV in nAMD.
基金Supported by General Program of National Natural Science Foundation of China(No.82471110)National Key Research and Development Program of China(No.2022YFC2502805)Postdoctoral Foundation of General Hospital of Central Theater Command(No.20210517KY04).
文摘AIM:To investigate the choroidal vascular index(CVI)and the choroidal structural changes beyond the subfoveal area(analyzed across a 20 mm×24 mm scanning area)in eyes with chronic central serous chorioretinopathy(cCSC)eyes with macular neovascularization(MNV)using ultra-widefield swept-source optical coherence tomography angiography(UWF SS-OCTA).METHODS:This retrospective comparative study included 46 cCSC with MNV eyes(With MNV group),52 cCSC without MNV eyes(Without MNV group),and 40 age-matched healthy controls.UWF SS-OCTA imaging with a 20 mm×24 mm protocol was used to quantify CVI across 9 subfields(superotemporal,superior,superonasal,temporal,central,nasal,inferotemporal,inferior,and inferonasal).The CVI was compared among the groups.RESULTS:With MNV group demonstrated significantly older mean age than Without MNV group(56.2±6.1 vs 47.5±8.6y,P<0.001).The CVI was significantly lower in the With MNV group than in the Without MNV group,except in the superotemporal,superior,and temporal regions(all P<0.05).Notably,despite MNV-associated CVI reductions,the With MNV group maintained a higher CVI than the control group in all 5 subfields(superior,temporal,central,inferior,and inferonasal;all P<0.05).In the central region,CONCLUSION:CVI decreases,and choroidal structural changes extend beyond the subfoveal area in cCSC with MNV eyes,providing with an imaging evidence for the important role of choroidal ischemia in the pathogenesis of MNV in cCSC.
基金supported by the Interdepartmental Research Project of Peking University First Hospital(No.2023IR27 to Liu Y)the Scientific Research Seed Fund of Peking University First Hospital(No.2023SF40 to Qiu J)+3 种基金the High Quality Clinical Research Project of Peking University First Hospital(No.2022CR75 to Gong K)the Beijing Natural Science Foundation(No.QY23068 to Deng R)the National Natural Science Foundation of China(No.82141103,No.82172617,and No.81872081 to Gong K)the Capital’s Funds for Health Improvement and Research(No.2022-2-4074 to Gong K).
文摘Objective:To explore clinicopathological predictors of adverse pathological changes(APCs)(upgrading,upstaging,and positive surgical margin[PSM])after robot-assisted radical prostatectomy(RARP)in clinical tumor stage 2c(cT2c)prostate cancer(PCa)patients.Methods:From January 2018 to December 2022,cT2cN0M0 PCa patients who underwent prostate biopsies and subsequent RARP at the Peking University First Hospital with an interval between biopsy and RARP of ≤90 days were included.Univariable and stepwise multivariable logistic regression analyses were performed to identify independent risk factors associated with APCs.Nomograms were constructed based on these predictive models.The performance of the nomograms was evaluated by receiver operating characteristic curves,decision curve analyses,and calibration plots.Results:A total of 423 eligible cT2cN0M0 PCa patients were included.The rates of upgrading,upstaging,and PSM in our cohortwere 33%,51%,and 35%,respectively.The stepwise multivariate logistic analysis suggested that PSA density and the percentage of positive cores in systematic biopsy were significantly associated with the occurrence of APCs.The score of the Prostate Imaging Reporting and Data System,PSA density,and the International Society of Urological Pathology grade group(IGG)of needle-biopsy specimens(or clinical IGG[cIGG])were significantly associated with upgrading.The PSA density,percentage of positive cores in systematic biopsy,and largest tumor percentage in all cores of each patient(LTP)were significantly associated with upstaging.The PSA density and LTP were significantly associatedwith the PSM.Based on these results,four nomogramswere developed.Receiver operating characteristic curves,decision curve analyses,and calibration plots implied that the nomograms exhibited excellent accuracy.Conclusion:The predictive models we developed could help to identify high-risk PCa early,and optimize clinical decisions of cT2cN0M0 PCa patients.
