The free-surface vortex is a rotational flow phenomenon characterized by two-phase coupling,formed by the rupture of surface fluid in the final stage of discharge.It is a significant concept with broad applications in...The free-surface vortex is a rotational flow phenomenon characterized by two-phase coupling,formed by the rupture of surface fluid in the final stage of discharge.It is a significant concept with broad applications in engineering fields like metallurgy and hydraulics.The basic concepts and characteristics of free-surface vortices were introduced,and their hazards in various fields were discussed.The development of theoretical and numerical models over recent decades was reviewed,and the factors affecting vortex formation and existing suppression methods were outlined.Finally,the key challenges and focus areas on the study of free-surface vortex were summarized.With the ongoing advancements in computational fluid dynamics and experimental technology,research on free-surface vortices will become more in depth and precise.Additionally,interdisciplinary cooperation and technological innovation are expected to achieve precise control and optimal design of free-surface vortices,offering more efficient and sustainable solutions for metallurgy and related engineering fields.展开更多
Multiple suppression is an important element of marine seismic data processing.Intelligent suppression of multiples us-ing artificial intelligence reduces labor costs,minimizes dependence on unknown prior information,...Multiple suppression is an important element of marine seismic data processing.Intelligent suppression of multiples us-ing artificial intelligence reduces labor costs,minimizes dependence on unknown prior information,and improves data processing ef-ficiency.In this study,we propose an intelligent method for suppressing marine seismic multiples using deep learning approaches.The proposed method enables the intelligent suppression of free-surface-related multiples from seismic records.Initially,we construct a multi-category marine seismic multiple dataset through finite difference forward modeling under different boundary conditions.We use various models and data augmentation methods,including sample rotation,noise addition,and random channel omission.Then,we apply depthwise separable convolution to develop our deep learning Mobilenet-Unet model.The Mobilenet-Unet framework sig-nificantly reduces the number of operations required for multiple elimination without sacrificing model performance,ultimately reali-zing the optimal multiple suppression model.The trained Mobilenet-Unet is applied to the test set for verification.Moreover,to deter-mine its generalization ability,it is implemented to seismic records containing multiples generated by two marine geophysical models that were not included in the training process.The performance of Mobilenet-Unet is also compared with that of different network structures.The results indicate that,despite its small size,our proposed Mobilenet-Unet deep learning model can rapidly and effective-ly separate multiples in marine seismic data,possessing reasonable generalization ability.展开更多
The deep convolutional neural network U-net has been introduced into adaptive subtraction, which is a critical step in effectively suppressing seismic multiples. The U-net approach has higher precision than the tradit...The deep convolutional neural network U-net has been introduced into adaptive subtraction, which is a critical step in effectively suppressing seismic multiples. The U-net approach has higher precision than the traditional linear regression approach. However, the existing 2D U-net approach with 2D data windows can not deal with elaborate discrepancies between the actual and simulated multiples along the gather direction. It may lead to erroneous preservation of primaries or generate obvious vestigial multiples, especially in complex media. To further enhance the multiple suppression accuracy, we present an adaptive subtraction approach utilizing 3D U-net architecture, which can adaptively separate primaries and multiples utilizing 3D windows. The utilization of 3D windows allows for enhanced depiction of spatial continuity and anisotropy of seismic events along the gather direction in comparison to 2D windows. The 3D U-net approach with 3D windows can more effectively preserve the continuity of primaries and manage the complex disparities between the actual and simulated multiples. The proposed 3D U-net approach exhibits 1 dB improvement in the signal-to-noise ratio compared to the 2D U-net approach, as observed in the synthesis data section, and exhibits more outstanding performance in the preservation of primaries and removal of residual multiples in both synthesis and reality data sections. Moreover, to expedite network training in our proposed 3D U-net approach we employ the transfer learning (TL) strategy by utilizing the network parameters of 3D U-net estimated in the preceding data segment as the initial network parameters of 3D U-net for the subsequent data segment. In the reality data section, the 3D U-net approach incorporating TL reduces the computational expense by 70% compared to the one without TL.展开更多
A rotating stopper-rod technique was proposed to suppress the formation of free-surface vortex in the tundish.The large eddy simulation model coupled with volume of fluid model was developed to study the steel–slag–...A rotating stopper-rod technique was proposed to suppress the formation of free-surface vortex in the tundish.The large eddy simulation model coupled with volume of fluid model was developed to study the steel–slag–gas three-phase flow behavior.The critical slag entrapment height of the free-surface vortex and mass of residual steel were predicted at different rotating speeds(30,60,90 and 120 r/min)of the rotating stopper-rod.The numerical model was verified by water model experiment.The results showed that by rotating the stopper-rod in the opposite direction of the vortex above the submerged entry nozzle,the formation of vortex can be effectively disturbed and the critical height of the free-surface vortex can be reduced.Particularly for the 2nd strand,when the rotating speeds are 30,60,90 and 120 r/min,the critical height of the free-surface vortex above the 2nd strand is 7.3,4.7,6.3 and 7.4 cm,respectively.A reasonable rotating speed should be 60 r/min,which can reduce about 2 tons of residual steel.Other rotating speeds just can reduce about 1.6 tons of residual steel.展开更多
BACKGROUND The incidence of malignant gastrointestinal(GI)tumors is increasing,and advancements in medical care have significantly improved patient survival rates.As a result,the number of cases involving multiple pri...BACKGROUND The incidence of malignant gastrointestinal(GI)tumors is increasing,and advancements in medical care have significantly improved patient survival rates.As a result,the number of cases involving multiple primary cancers(MPC)has also increased.The rarity of MPC and the absence of sensitive and specific dia-gnostic markers often lead to missed or incorrect diagnoses.It is,therefore,of vital importance to improve the vigilance of clinicians and the accurate diagnosis of this disease.Patients with GI malignancies face a higher relative risk of deve-loping additional primary malignant tumors compared to those with other systemic tumors.Vigilant monitoring and follow-up are crucial,especially for high-risk groups,which include older adults,men,those with addictions to alcohol and tobacco,those with a family history of tumors,and those who have undergone radiotherapy.CASE SUMMARY In this article,we report three cases of MPC,each involving malignant tumors of the GI tract as the initial primary carcinoma,offering insights that may aid in effectively managing similar cases.CONCLUSION Patients with GI malignancies face a higher MPC risk.Developing screening and follow-up protocols may enhance detection and treatment outcomes.展开更多
Combined with elastic network model(ENM),the perturbation response scanning(PRS)has emerged as a robust technique for pinpointing allosteric interactions within proteins.Here,we proposed the PRS analysis of drug-targe...Combined with elastic network model(ENM),the perturbation response scanning(PRS)has emerged as a robust technique for pinpointing allosteric interactions within proteins.Here,we proposed the PRS analysis of drug-target networks(DTNs),which could provide a promising avenue in network medicine.We demonstrated the utility of the method by introducing a deep learning and network perturbation-based framework,for drug repurposing of multiple sclerosis(MS).First,the MS comorbidity network was constructed by performing a random walk with restart algorithm based on shared genes between MS and other diseases as seed nodes.Then,based on topological analysis and functional annotation,the neurotransmission module was identified as the“therapeutic module”of MS.Further,perturbation scores of drugs on the module were calculated by constructing the DTN and introducing the PRS analysis,giving a list of repurposable drugs for MS.Mechanism of action analysis both at pathway and structural levels screened dihydroergocristine as a candidate drug of MS by targeting a serotonin receptor of se-rotonin 2B receptor(HTR2B).Finally,we established a cuprizone-induced chronic mouse model to evaluate the alteration of HTR2B in mouse brain regions and observed that HTR2B was significantly reduced in the cuprizone-induced mouse cortex.These findings proved that the network perturbation modeling is a promising avenue for drug repurposing of MS.As a useful systematic method,our approach can also be used to discover the new molecular mechanism and provide effective candidate drugs for other complex diseases.展开更多
Mononuclear macrophage infiltration in the central nervous system is a prominent feature of neuroinflammation. Recent studies on the pathogenesis and progression of multiple sclerosis have highlighted the multiple rol...Mononuclear macrophage infiltration in the central nervous system is a prominent feature of neuroinflammation. Recent studies on the pathogenesis and progression of multiple sclerosis have highlighted the multiple roles of mononuclear macrophages in the neuroinflammatory process. Monocytes play a significant role in neuroinflammation, and managing neuroinflammation by manipulating peripheral monocytes stands out as an effective strategy for the treatment of multiple sclerosis, leading to improved patient outcomes. This review outlines the steps involved in the entry of myeloid monocytes into the central nervous system that are targets for effective intervention: the activation of bone marrow hematopoiesis, migration of monocytes in the blood, and penetration of the blood–brain barrier by monocytes. Finally, we summarize the different monocyte subpopulations and their effects on the central nervous system based on phenotypic differences. As activated microglia resemble monocyte-derived macrophages, it is important to accurately identify the role of monocyte-derived macrophages in disease. Depending on the roles played by monocyte-derived macrophages at different stages of the disease, several of these processes can be interrupted to limit neuroinflammation and improve patient prognosis. Here, we discuss possible strategies to target monocytes in neurological diseases, focusing on three key aspects of monocyte infiltration into the central nervous system, to provide new ideas for the treatment of neurodegenerative diseases.展开更多
This study numerically examines the heat and mass transfer characteristics of two ternary nanofluids via converging and diverg-ing channels.Furthermore,the study aims to assess two ternary nanofluids combinations to d...This study numerically examines the heat and mass transfer characteristics of two ternary nanofluids via converging and diverg-ing channels.Furthermore,the study aims to assess two ternary nanofluids combinations to determine which configuration can provide better heat and mass transfer and lower entropy production,while ensuring cost efficiency.This work bridges the gap be-tween academic research and industrial feasibility by incorporating cost analysis,entropy generation,and thermal efficiency.To compare the velocity,temperature,and concentration profiles,we examine two ternary nanofluids,i.e.,TiO_(2)+SiO_(2)+Al_(2)O_(3)/H_(2)O and TiO_(2)+SiO_(2)+Cu/H_(2)O,while considering the shape of nanoparticles.The velocity slip and Soret/Dufour effects are taken into consideration.Furthermore,regression analysis for Nusselt and Sherwood numbers of the model is carried out.The Runge-Kutta fourth-order method with shooting technique is employed to acquire the numerical solution of the governed system of ordinary differential equations.The flow pattern attributes of ternary nanofluids are meticulously examined and simulated with the fluc-tuation of flow-dominating parameters.Additionally,the influence of these parameters is demonstrated in the flow,temperature,and concentration fields.For variation in Eckert and Dufour numbers,TiO_(2)+SiO_(2)+Al_(2)O_(3)/H_(2)O has a higher temperature than TiO_(2)+SiO_(2)+Cu/H_(2)O.The results obtained indicate that the ternary nanofluid TiO_(2)+SiO_(2)+Al_(2)O_(3)/H_(2)O has a higher heat transfer rate,lesser entropy generation,greater mass transfer rate,and lower cost than that of TiO_(2)+SiO_(2)+Cu/H_(2)O ternary nanofluid.展开更多
In order to save manpower and time costs,and to achieve simultaneous detection of multiple animal-derived components in meat and meat products,this study used multiple nucleotide polymorphism(MNP)marker technology bas...In order to save manpower and time costs,and to achieve simultaneous detection of multiple animal-derived components in meat and meat products,this study used multiple nucleotide polymorphism(MNP)marker technology based on the principle of high-throughput sequencing,and established a multi-locus 10 animalderived components identification method of cattle,goat,sheep,donkey,horse,chicken,duck,goose,pigeon,quail in meat and meat products.The specific loci of each species could be detected and the species could be accurately identified,including 5 loci for cattle and duck,3 loci for sheep,9 loci for chicken and horse,10 loci for goose and pigeon,6 loci for quail and 1 locus for donkey and goat,and an adulteration model was established to simulate commercially available samples.The results showed that the method established in this study had high throughput,good repeatability and accuracy,and was able to identify 10 animalderived components simultaneously with 100%repeatability accuracy.The detection limit was 0.1%(m/m)in simulated samples of chicken,duck and horse.Using the method established in this study to test commercially available samples,4 samples from 14 commercially available samples were detected to be inconsistent with the labels,of which 2 did not contain the target ingredient and 2 were adulterated with small amounts of other ingredients.展开更多
Male infertility can result from impaired sperm motility caused by multiple morphological abnormalities of the flagella(MMAF).Distinct projections encircling the central microtubules of the spermatozoal axoneme play p...Male infertility can result from impaired sperm motility caused by multiple morphological abnormalities of the flagella(MMAF).Distinct projections encircling the central microtubules of the spermatozoal axoneme play pivotal roles in flagellar bending and spermatozoal movement.Mammalian sperm-associated antigen 17(SPAG17)encodes a conserved axonemal protein of cilia and flagella,forming part of the C1a projection of the central apparatus,with functions related to ciliary/flagellar motility,skeletal growth,and male fertility.This study investigated two novel homozygous SPAG17 mutations(M1:NM_206996.2,c.829+1G>T,p.Asp212_Glu276del;and M2:c.2120del,p.Leu707*)identified in four infertile patients from two consanguineous Pakistani families.These patients displayed the MMAF phenotype confirmed by Papanicolaou staining and scanning electron microscopy assays of spermatozoa.Quantitative real-time polymerase chain reaction(PCR)of patients’spermatozoa also revealed a significant decrease in SPAG17 mRNA expression,and immunofluorescence staining showed the absence of SPAG17 protein signals along the flagella.However,no apparent ciliary-related symptoms or skeletal malformations were observed in the chest X-rays of any of the patients.Transmission electron microscopy of axoneme cross-sections from the patients showed incomplete C1a projection and a higher frequency of missing microtubule doublets 1 and 9 compared with those from fertile controls.Immunofluorescence staining and Western blot analyses of spermatogenesis-associated protein 17(SPATA17),a component of the C1a projection,and sperm-associated antigen 6(SPAG6),a marker of the spring layer,revealed disrupted expression of both proteins in the patients’spermatozoa.Altogether,these findings demonstrated that SPAG17 maintains the integrity of spermatozoal flagellar axoneme,expanding the phenotypic spectrum of SPAG17 mutations in humans.展开更多
Objective:Multiple myeloma(MM)is a hematologically malignant clonal plasma cell disease.This study aims to explore the association between immunophenotypes and prognosis in patients with MM,to determine whether the ex...Objective:Multiple myeloma(MM)is a hematologically malignant clonal plasma cell disease.This study aims to explore the association between immunophenotypes and prognosis in patients with MM,to determine whether the expression of CD45 and CD200 is related to the prognosis of newly diagnosed MM(NDMM)patients,and to evaluate the significance of the combined expression of CD45 and CD200 in NDMM.Methods:A total of 123 NDMM patients admitted to Shengjing Hospital of China Medical University from July 2015 to August 2019 were enrolled.Five key immunophenotypic markers(including CD38,CD138,CD45,CD56,and CD200)were screened through flow cytometry and identified using random forest analysis and univariate Cox regression analysis.Patients were divided into 3 groups:Group A,CD45 and CD200 double-positive;Group B,CD45 or CD200 single-positive;Group C,CD45 and CD200 double-negative.Kaplan-Meier curves were used to analyze overall survival(OS)and progression-free survival(PFS)across groups.Multivariate Cox regression was performed to evaluate prognostic factors,and a nomogram was constructed based on these results.Results:The OS and PFS of single-positive groups for CD38,CD138,CD45,CD56,and CD200 were all shorter than those of their respective single-negative groups(all P<0.05).Significant differences were observed in OS(P<0.001)and PFS(P=0.001)among Groups A,B,and C.Group A had shorter OS and PFS(all P=0.001)compared to the Group B+C(cases from Group B and Group C were combined).CD45 and CD200 double-positive was an independent prognostic factor for NDMM[hazard ratio(HR)=2.178,95%confidence interval(CI)1.048 to 4.529;P=0.037].The nomogram and calibration curves constructed from multivariate Cox regression analysis demonstrated good concordance(concordance index=0.706;95%CI 0.661 to 0.751).Conclusion:NDMM patients with double-positive expression of CD45 and CD200 have significantly shorter OS and PFS.Compared with the use of either marker alone,the combined assessment of CD45 and CD200 may provide better prognostic stratification for MM patients.展开更多
The boundness and compactness of products of multiplication,composition and differentiation on weighted Bergman spaces in the unit ball are studied.We define the differentiation operator on the space of holomorphic fu...The boundness and compactness of products of multiplication,composition and differentiation on weighted Bergman spaces in the unit ball are studied.We define the differentiation operator on the space of holomorphic functions in the unit ball by radial derivative.Then we extend the Sharma's results.展开更多
The charge carrier transport and recombination dynamics in the quantum dots-based light-emitting diodes(QLEDs)featuring multiple emitting layers(M-EMLs)has a great impact on the device performance.In this work,QLEDs b...The charge carrier transport and recombination dynamics in the quantum dots-based light-emitting diodes(QLEDs)featuring multiple emitting layers(M-EMLs)has a great impact on the device performance.In this work,QLEDs based on M-EMLs separated by polyethyleneimine ethoxylated(PEIE)layer with different stacking sequences of blue(B),green(G),and red(R)QDs layer were used to intuitively explore the injection,transportation and recombination processes of the charge carriers in QLEDs by using the time-resolved electroluminescence(TrEL)spectra.From the TrEL spectra mea-surements,green and red emissions were obtained first in the QLEDs with the EMLs sequences of G/PEIE/B/PEIE/R and B/PEIE/R/PEIE/G along the direction of light emission,respectively.While the QLEDs adopt EMLs sequences of B/PEIE/G/PEIE/R,the blue,green and red emissions were obtained nearly at the same time.The above phenomenon can be attributed to different charge carrier transmission and radiation recombination process in the EMLs due to different valence band offsets and conduction band offsets between R-,G-and B-QDs by using different sequences of EMLs.White emission with coordi-nates of(0.31,0.31)and correlated color temperature(CCT)of 5916 K was obtained in the QLEDs with the EMLs se-quences of B/PEIE/G/PEIE/R,which can be attributed to the relative uniform emission of B-,G-and R-QDs due to the effec-tive injection and radiation recombination of charge carriers in each of the EMLs.The above results have great significance for further understanding and improving the performance of QLEDs with M-EMLs.展开更多
Dear Editor,This letter addresses the impulse game problem for a general scope of deterministic,multi-player,nonzero-sum differential games wherein all participants adopt impulse controls.Our objective is to formulate...Dear Editor,This letter addresses the impulse game problem for a general scope of deterministic,multi-player,nonzero-sum differential games wherein all participants adopt impulse controls.Our objective is to formulate this impulse game problem with the modified objective function including interaction costs among the players in a discontinuous fashion,and subsequently,to derive a verification theorem for identifying the feedback Nash equilibrium strategy.展开更多
This paper introduces an optimized planning approach for integrating photovoltaic as distributed generation (PV-DG) into the radial distribution power systems, utilizing exhaustive load flow (ELF), loss sensitivity fa...This paper introduces an optimized planning approach for integrating photovoltaic as distributed generation (PV-DG) into the radial distribution power systems, utilizing exhaustive load flow (ELF), loss sensitivity factor (LSF), genetic algorithms (GA) methods, and numerical method based on LSF. The methodology aims to determine the optimal allocation and sizing of multiple PV-DG to minimize power loss through time series power flow analysis. An approach utilizing continuous sensitivity analysis is developed and inherently leverages power flow and loss equations to compute LSF of all buses in the system towards employing a dynamic PV-DG model for more accurate results. The algorithm uses a numerical grid search method to optimize PV-DG placement in a power distribution system, focusing on minimizing system losses. It combines iterative analysis, sensitivity assessment, and comprehensive visualization to identify and present the optimal PV-DG configurations. The present-ed algorithms are verified through co-simulation framework combining MATLAB and OpenDSS to carry out analysis for 12-bus radial distribution test system. The proposed numerical method is compared with other algorithms, such as ELF, LSF methods, and Genetic Algorithms (GA). Results show that the proposed numerical method performs well in comparison with LSF and ELF solutions.展开更多
Multiple evanescent white dot syndrome(MEWDS)is an inflammatory fundus disease primarily affecting the outer retina.It is characterized by transient yellow-white dots on the outer retina.Although the exact pathogenesi...Multiple evanescent white dot syndrome(MEWDS)is an inflammatory fundus disease primarily affecting the outer retina.It is characterized by transient yellow-white dots on the outer retina.Although the exact pathogenesis remains unclear,the progress in multimodal imaging(MMI)has enhanced our understanding of MEWDS.Most cases of MEWDS are idiopathic,lacking a definite cause,and can spontaneously recover;these are what we term classic MEWDS.Consequently,MEWDS is often referred to as the“common cold of the retina”.Simultaneously,patients with other disorders may present with varying degrees of manifestations similar to MEWDS.The resemblance in clinical or imaging findings can lead to misdiagnosis and inappropriate treatment.These MEWDS-like presentations are actually caused by other systemic or ocular disorders with diverse mechanisms.Thus,they differ from classic MEWDS in certain aspects.Using the keywords“MEWDSlike”and“Secondary MEWDS”,we searched for all relevant studies published in the PubMed database from January 2021 to January 2024.Subsequently,we retrospectively summarized the clinical and imaging characteristics of MEWDS,along with the manifestations in other diseases that resembled those of MEWDS,and compared classic MEWDS with these similar presentations.Based on our review,we classified such similar presentations under other conditions into two categories and summarized their features for differential diagnosis.We recommend paying close attention to patients suspected of having MEWDS,as there may be more serious systemic or ocular disorders that require prompt treatment.展开更多
Multiple myeloma(MM),one of the most common hemato logical neoplasms worldwide,originates from malignant plasma cells in the bone marrow.MM remains an incurable disease,although continued treatment advancements have m...Multiple myeloma(MM),one of the most common hemato logical neoplasms worldwide,originates from malignant plasma cells in the bone marrow.MM remains an incurable disease,although continued treatment advancements have markedly increased overall survival.Many patients with MM eventually experience relapse or become treatment-refractory1.Patients with relapsed or refractory multiple myeloma(RRMM)become progressively more challenging to manage and have poor prognosis2.展开更多
Active inflammation in“inactive”progressive multiple sclerosis:Traditionally,the distinction between relapsing-remitting multiple sclerosis and progressive multiple sclerosis(PMS)has been framed as an inflammatory v...Active inflammation in“inactive”progressive multiple sclerosis:Traditionally,the distinction between relapsing-remitting multiple sclerosis and progressive multiple sclerosis(PMS)has been framed as an inflammatory versus degenerative dichotomy.This was based on a broad misconception regarding essentially all neurodegenerative conditions,depicting the degenerative process as passive and immune-independent occurring as a late byproduct of active inflammation in the central nervous system(CNS),which is(solely)systemically driven.展开更多
Background:Multiple sclerosis(MS)is a chronic disease of the central nervous system(CNS),exhibiting hallmarks of both inflammation and neurodegeneration and with limited treatment options.The intricate nature of MS pa...Background:Multiple sclerosis(MS)is a chronic disease of the central nervous system(CNS),exhibiting hallmarks of both inflammation and neurodegeneration and with limited treatment options.The intricate nature of MS pathophysiology and its variable progression pose severe challenges for the development of effective therapies.The experimental autoimmune encephalomyelitis(EAE)MS model,in its most common form,is an aggressive disease,which is not representative of the MS course and offers a limited time window for drug evaluation.This study aimed to generate an attenuated EAE variant,which extends the clinical testing window while preserving the high incidence of the standard EAE model.Methods:Components of the EAE induction protocol were titrated to develop a milder disease profile.In a subsequent drug trial using the MS medication fingolimod hydrochloride(FTY,Gilenya),the new variant was validated under prophylactic and therapeutic treatment regimens.Results:The attenuated EAE variant retains the standard hallmarks of neuroinflammation and,crucially,significantly extends the time frame for clinical drug testing.Unlike the standard variant,where FTY efficacy could only be demonstrated by prophylactic treatment,the attenuated variant facilitated differentiation of drug effects by therapeutic treatment initiated early in the acute phase of disease.Conclusion:The new EAE variant is suitable for use in preclinical assessment of candidate therapeutics and the identification of targetable molecular mechanisms underpinning disease development and progression.This study illustrates the importance of optimizing and refining the experimental tool to enhance the translational success of the candidate therapeutics for MS.展开更多
BACKGROUND Metachronous multiple esophageal squamous cell carcinomas(ESCCs)may occur in some patients after endoscopic resection.Multiple dysplastic lesions in the esophagus increase risk of multiple squamous cell car...BACKGROUND Metachronous multiple esophageal squamous cell carcinomas(ESCCs)may occur in some patients after endoscopic resection.Multiple dysplastic lesions in the esophagus increase risk of multiple squamous cell carcinomas(SCCs).Endoscopic imaging technology such as narrow band imaging(NBI),can detect early SCC.Lugol chromoendoscopy is also the conventional standard technique for detecting superficial ESCC.However,little is known about the interval from the first SCC to the metachronous SCC.Effective methods to prevent multiple metachronous SCCs are needed in survivors of esophageal SCC.CASE SUMMARY A 56-year-old man showed a slightly elevated reddish area in the middle thoracic esophagus at 30 cm from the incisors on gastroscopy for routine examination.Esophageal mucosa lesion was about 2.5 cm.NBI and magnifying gastroscopy confirmed intra-epithelial papillary loop type B-1 according to the Japan Esophageal Society Classification.Lugol chromoendoscopy was used to evaluate the dysplastic squamous epithelium in the esophagus.Biopsy pathology revealed severe dysplastic squamous epithelium.Computed tomography showed no lymph node metastasis.His complete blood test and tumor markers were within reference values.He had no history of alcohol consumption and smoking.Mucosal lesion was dissected by endoscopic submucosal dissection(ESD).Postoperative pathological results showed moderately differentiated squamous carcinoma.No cancer thrombus was seen in the vasculature,and the surrounding cut edge was not involved.The patient underwent radiotherapy within 2 months after ESD.The multiple Lugol-voiding lesions disappeared,and enhanced chest computed tomography revealed no lymph node metastasis.CONCLUSION This is the first case of multiple dysplastic lesions of esophagus cured by radiotherapy.Radiotherapy after minimally invasive endoscopic treatment might be a safe and effective optional therapeutic strategy to prevent metachronous multiple esophageal SCCs.展开更多
基金supported by the National Natural Science Foundation of China(Grant No.52474339)Anhui Province Outstanding Research and Innovation Team in Higher Education Institutions(Grant No.2022AH010024).
文摘The free-surface vortex is a rotational flow phenomenon characterized by two-phase coupling,formed by the rupture of surface fluid in the final stage of discharge.It is a significant concept with broad applications in engineering fields like metallurgy and hydraulics.The basic concepts and characteristics of free-surface vortices were introduced,and their hazards in various fields were discussed.The development of theoretical and numerical models over recent decades was reviewed,and the factors affecting vortex formation and existing suppression methods were outlined.Finally,the key challenges and focus areas on the study of free-surface vortex were summarized.With the ongoing advancements in computational fluid dynamics and experimental technology,research on free-surface vortices will become more in depth and precise.Additionally,interdisciplinary cooperation and technological innovation are expected to achieve precise control and optimal design of free-surface vortices,offering more efficient and sustainable solutions for metallurgy and related engineering fields.
基金supported by the Key Laboratory of Ma-rine Mineral Resources,Ministry of Natural Resources,Guangzhou(No.KLMMR-2022-G09)the Guangzhou Ba-sic Research Program-Basic and Basic Applied Research Project(No.2023A04J0917)the PI Project of South-ern Marine Science and Engineering Guangdong Labora-tory(Guangzhou)(No.GML2020GD0802).
文摘Multiple suppression is an important element of marine seismic data processing.Intelligent suppression of multiples us-ing artificial intelligence reduces labor costs,minimizes dependence on unknown prior information,and improves data processing ef-ficiency.In this study,we propose an intelligent method for suppressing marine seismic multiples using deep learning approaches.The proposed method enables the intelligent suppression of free-surface-related multiples from seismic records.Initially,we construct a multi-category marine seismic multiple dataset through finite difference forward modeling under different boundary conditions.We use various models and data augmentation methods,including sample rotation,noise addition,and random channel omission.Then,we apply depthwise separable convolution to develop our deep learning Mobilenet-Unet model.The Mobilenet-Unet framework sig-nificantly reduces the number of operations required for multiple elimination without sacrificing model performance,ultimately reali-zing the optimal multiple suppression model.The trained Mobilenet-Unet is applied to the test set for verification.Moreover,to deter-mine its generalization ability,it is implemented to seismic records containing multiples generated by two marine geophysical models that were not included in the training process.The performance of Mobilenet-Unet is also compared with that of different network structures.The results indicate that,despite its small size,our proposed Mobilenet-Unet deep learning model can rapidly and effective-ly separate multiples in marine seismic data,possessing reasonable generalization ability.
基金supported by National Natural Science Foundation of China(42364008,41804110)in part by Guizhou Provincial Basic Research Program(Natural Science)(ZK[2022]060)+1 种基金in part by China Postdoctoral Science Foundation(2022M723127)in part by Youth Innovation Team Project of Shandong Provincial Education Department(2022KJ141).
文摘The deep convolutional neural network U-net has been introduced into adaptive subtraction, which is a critical step in effectively suppressing seismic multiples. The U-net approach has higher precision than the traditional linear regression approach. However, the existing 2D U-net approach with 2D data windows can not deal with elaborate discrepancies between the actual and simulated multiples along the gather direction. It may lead to erroneous preservation of primaries or generate obvious vestigial multiples, especially in complex media. To further enhance the multiple suppression accuracy, we present an adaptive subtraction approach utilizing 3D U-net architecture, which can adaptively separate primaries and multiples utilizing 3D windows. The utilization of 3D windows allows for enhanced depiction of spatial continuity and anisotropy of seismic events along the gather direction in comparison to 2D windows. The 3D U-net approach with 3D windows can more effectively preserve the continuity of primaries and manage the complex disparities between the actual and simulated multiples. The proposed 3D U-net approach exhibits 1 dB improvement in the signal-to-noise ratio compared to the 2D U-net approach, as observed in the synthesis data section, and exhibits more outstanding performance in the preservation of primaries and removal of residual multiples in both synthesis and reality data sections. Moreover, to expedite network training in our proposed 3D U-net approach we employ the transfer learning (TL) strategy by utilizing the network parameters of 3D U-net estimated in the preceding data segment as the initial network parameters of 3D U-net for the subsequent data segment. In the reality data section, the 3D U-net approach incorporating TL reduces the computational expense by 70% compared to the one without TL.
基金the National Natural Science Foundation of China(52004191)the China Postdoctoral Science Foundation(2022M711120)+1 种基金the Science and Technology Research Project of Education Department of Hubei Province(B2022020)Besides,the numerical calculation is supported by High-Performance Computing Center of Wuhan University of Science and Technology.
文摘A rotating stopper-rod technique was proposed to suppress the formation of free-surface vortex in the tundish.The large eddy simulation model coupled with volume of fluid model was developed to study the steel–slag–gas three-phase flow behavior.The critical slag entrapment height of the free-surface vortex and mass of residual steel were predicted at different rotating speeds(30,60,90 and 120 r/min)of the rotating stopper-rod.The numerical model was verified by water model experiment.The results showed that by rotating the stopper-rod in the opposite direction of the vortex above the submerged entry nozzle,the formation of vortex can be effectively disturbed and the critical height of the free-surface vortex can be reduced.Particularly for the 2nd strand,when the rotating speeds are 30,60,90 and 120 r/min,the critical height of the free-surface vortex above the 2nd strand is 7.3,4.7,6.3 and 7.4 cm,respectively.A reasonable rotating speed should be 60 r/min,which can reduce about 2 tons of residual steel.Other rotating speeds just can reduce about 1.6 tons of residual steel.
基金Supported by Gansu Provincial Natural Science Foundation,No.21JR1RA010In-Hospital Research Fund of Gansu Provincial Hospital,No.23GSSYD-5.
文摘BACKGROUND The incidence of malignant gastrointestinal(GI)tumors is increasing,and advancements in medical care have significantly improved patient survival rates.As a result,the number of cases involving multiple primary cancers(MPC)has also increased.The rarity of MPC and the absence of sensitive and specific dia-gnostic markers often lead to missed or incorrect diagnoses.It is,therefore,of vital importance to improve the vigilance of clinicians and the accurate diagnosis of this disease.Patients with GI malignancies face a higher relative risk of deve-loping additional primary malignant tumors compared to those with other systemic tumors.Vigilant monitoring and follow-up are crucial,especially for high-risk groups,which include older adults,men,those with addictions to alcohol and tobacco,those with a family history of tumors,and those who have undergone radiotherapy.CASE SUMMARY In this article,we report three cases of MPC,each involving malignant tumors of the GI tract as the initial primary carcinoma,offering insights that may aid in effectively managing similar cases.CONCLUSION Patients with GI malignancies face a higher MPC risk.Developing screening and follow-up protocols may enhance detection and treatment outcomes.
基金supported by the National Natural Science Foundation of China(Grant Nos.:32271292,31872723,32200778,and 22377089)the Jiangsu Students Innovation and Entrepre-neurship Training Program,China(Program No.:202210285081Z)+6 种基金the Project of MOE Key Laboratory of Geriatric Diseases and Immunology,China(Project No.:JYN202404)Proj-ect Funded by the Priority Academic Program Development(PAPD)of Jiangsu Higher Education Institutions,Natural Science Foundation of Jiangsu Province,China(Project No.:BK20220494)Suzhou Medical and Health Technology Innovation Project,China(Grant No.:SKY2022107)the Clinical Research Center of Neuro-logical Disease in The Second Affiliated Hospital of Soochow University,China(Grant No.:ND2022A04)State Key Laboratory of Drug Research(Grant No.:SKLDR-2023-KF-05)Jiangsu Shuang-chuang Program for Doctor,Young Science Talents Promotion Project of Jiangsu Science and Technology Association(Program No.:TJ-2023-019)Young Science Talents Promotion Project of Suzhou Science and Technology Association,Suzhou International Joint Laboratory for Diagnosis and Treatment of Brain Diseases,and startup funding(Grant Nos.:NH21500221,NH21500122,and NH21500123)to Qifei Cong.
文摘Combined with elastic network model(ENM),the perturbation response scanning(PRS)has emerged as a robust technique for pinpointing allosteric interactions within proteins.Here,we proposed the PRS analysis of drug-target networks(DTNs),which could provide a promising avenue in network medicine.We demonstrated the utility of the method by introducing a deep learning and network perturbation-based framework,for drug repurposing of multiple sclerosis(MS).First,the MS comorbidity network was constructed by performing a random walk with restart algorithm based on shared genes between MS and other diseases as seed nodes.Then,based on topological analysis and functional annotation,the neurotransmission module was identified as the“therapeutic module”of MS.Further,perturbation scores of drugs on the module were calculated by constructing the DTN and introducing the PRS analysis,giving a list of repurposable drugs for MS.Mechanism of action analysis both at pathway and structural levels screened dihydroergocristine as a candidate drug of MS by targeting a serotonin receptor of se-rotonin 2B receptor(HTR2B).Finally,we established a cuprizone-induced chronic mouse model to evaluate the alteration of HTR2B in mouse brain regions and observed that HTR2B was significantly reduced in the cuprizone-induced mouse cortex.These findings proved that the network perturbation modeling is a promising avenue for drug repurposing of MS.As a useful systematic method,our approach can also be used to discover the new molecular mechanism and provide effective candidate drugs for other complex diseases.
基金supported by the National Natural Science Foundation of China,Nos.82060219,82271234the Natural Science Foundation of Jiangxi Province,Nos.20212ACB216009,20212BAB216048+1 种基金Jiangxi Province Thousands of Plans,No.jxsq2019201023Youth Team Project of the Second Affiliated Hospital of Nanchang University,No.2019YNTD12003(all to FH)。
文摘Mononuclear macrophage infiltration in the central nervous system is a prominent feature of neuroinflammation. Recent studies on the pathogenesis and progression of multiple sclerosis have highlighted the multiple roles of mononuclear macrophages in the neuroinflammatory process. Monocytes play a significant role in neuroinflammation, and managing neuroinflammation by manipulating peripheral monocytes stands out as an effective strategy for the treatment of multiple sclerosis, leading to improved patient outcomes. This review outlines the steps involved in the entry of myeloid monocytes into the central nervous system that are targets for effective intervention: the activation of bone marrow hematopoiesis, migration of monocytes in the blood, and penetration of the blood–brain barrier by monocytes. Finally, we summarize the different monocyte subpopulations and their effects on the central nervous system based on phenotypic differences. As activated microglia resemble monocyte-derived macrophages, it is important to accurately identify the role of monocyte-derived macrophages in disease. Depending on the roles played by monocyte-derived macrophages at different stages of the disease, several of these processes can be interrupted to limit neuroinflammation and improve patient prognosis. Here, we discuss possible strategies to target monocytes in neurological diseases, focusing on three key aspects of monocyte infiltration into the central nervous system, to provide new ideas for the treatment of neurodegenerative diseases.
基金supported by DST-FIST(Government of India)(Grant No.SR/FIST/MS-1/2017/13)and Seed Money Project(Grant No.DoRDC/733).
文摘This study numerically examines the heat and mass transfer characteristics of two ternary nanofluids via converging and diverg-ing channels.Furthermore,the study aims to assess two ternary nanofluids combinations to determine which configuration can provide better heat and mass transfer and lower entropy production,while ensuring cost efficiency.This work bridges the gap be-tween academic research and industrial feasibility by incorporating cost analysis,entropy generation,and thermal efficiency.To compare the velocity,temperature,and concentration profiles,we examine two ternary nanofluids,i.e.,TiO_(2)+SiO_(2)+Al_(2)O_(3)/H_(2)O and TiO_(2)+SiO_(2)+Cu/H_(2)O,while considering the shape of nanoparticles.The velocity slip and Soret/Dufour effects are taken into consideration.Furthermore,regression analysis for Nusselt and Sherwood numbers of the model is carried out.The Runge-Kutta fourth-order method with shooting technique is employed to acquire the numerical solution of the governed system of ordinary differential equations.The flow pattern attributes of ternary nanofluids are meticulously examined and simulated with the fluc-tuation of flow-dominating parameters.Additionally,the influence of these parameters is demonstrated in the flow,temperature,and concentration fields.For variation in Eckert and Dufour numbers,TiO_(2)+SiO_(2)+Al_(2)O_(3)/H_(2)O has a higher temperature than TiO_(2)+SiO_(2)+Cu/H_(2)O.The results obtained indicate that the ternary nanofluid TiO_(2)+SiO_(2)+Al_(2)O_(3)/H_(2)O has a higher heat transfer rate,lesser entropy generation,greater mass transfer rate,and lower cost than that of TiO_(2)+SiO_(2)+Cu/H_(2)O ternary nanofluid.
基金financially supported by National Key R&D Program(2021YFF0701905)。
文摘In order to save manpower and time costs,and to achieve simultaneous detection of multiple animal-derived components in meat and meat products,this study used multiple nucleotide polymorphism(MNP)marker technology based on the principle of high-throughput sequencing,and established a multi-locus 10 animalderived components identification method of cattle,goat,sheep,donkey,horse,chicken,duck,goose,pigeon,quail in meat and meat products.The specific loci of each species could be detected and the species could be accurately identified,including 5 loci for cattle and duck,3 loci for sheep,9 loci for chicken and horse,10 loci for goose and pigeon,6 loci for quail and 1 locus for donkey and goat,and an adulteration model was established to simulate commercially available samples.The results showed that the method established in this study had high throughput,good repeatability and accuracy,and was able to identify 10 animalderived components simultaneously with 100%repeatability accuracy.The detection limit was 0.1%(m/m)in simulated samples of chicken,duck and horse.Using the method established in this study to test commercially available samples,4 samples from 14 commercially available samples were detected to be inconsistent with the labels,of which 2 did not contain the target ingredient and 2 were adulterated with small amounts of other ingredients.
基金supported by the National Natural Science Foundation of China(No.82171599 and No.32270901)the National Key Research and Developmental Program of China(2022YFC2702601 and 2022YFA0806303)the Global Select Project(DJKLX-2022010)of the Institute of Health and Medicine,Hefei Comprehensive National Science Center.
文摘Male infertility can result from impaired sperm motility caused by multiple morphological abnormalities of the flagella(MMAF).Distinct projections encircling the central microtubules of the spermatozoal axoneme play pivotal roles in flagellar bending and spermatozoal movement.Mammalian sperm-associated antigen 17(SPAG17)encodes a conserved axonemal protein of cilia and flagella,forming part of the C1a projection of the central apparatus,with functions related to ciliary/flagellar motility,skeletal growth,and male fertility.This study investigated two novel homozygous SPAG17 mutations(M1:NM_206996.2,c.829+1G>T,p.Asp212_Glu276del;and M2:c.2120del,p.Leu707*)identified in four infertile patients from two consanguineous Pakistani families.These patients displayed the MMAF phenotype confirmed by Papanicolaou staining and scanning electron microscopy assays of spermatozoa.Quantitative real-time polymerase chain reaction(PCR)of patients’spermatozoa also revealed a significant decrease in SPAG17 mRNA expression,and immunofluorescence staining showed the absence of SPAG17 protein signals along the flagella.However,no apparent ciliary-related symptoms or skeletal malformations were observed in the chest X-rays of any of the patients.Transmission electron microscopy of axoneme cross-sections from the patients showed incomplete C1a projection and a higher frequency of missing microtubule doublets 1 and 9 compared with those from fertile controls.Immunofluorescence staining and Western blot analyses of spermatogenesis-associated protein 17(SPATA17),a component of the C1a projection,and sperm-associated antigen 6(SPAG6),a marker of the spring layer,revealed disrupted expression of both proteins in the patients’spermatozoa.Altogether,these findings demonstrated that SPAG17 maintains the integrity of spermatozoal flagellar axoneme,expanding the phenotypic spectrum of SPAG17 mutations in humans.
基金supported by the National Natural Science Foundation,China(81870166).
文摘Objective:Multiple myeloma(MM)is a hematologically malignant clonal plasma cell disease.This study aims to explore the association between immunophenotypes and prognosis in patients with MM,to determine whether the expression of CD45 and CD200 is related to the prognosis of newly diagnosed MM(NDMM)patients,and to evaluate the significance of the combined expression of CD45 and CD200 in NDMM.Methods:A total of 123 NDMM patients admitted to Shengjing Hospital of China Medical University from July 2015 to August 2019 were enrolled.Five key immunophenotypic markers(including CD38,CD138,CD45,CD56,and CD200)were screened through flow cytometry and identified using random forest analysis and univariate Cox regression analysis.Patients were divided into 3 groups:Group A,CD45 and CD200 double-positive;Group B,CD45 or CD200 single-positive;Group C,CD45 and CD200 double-negative.Kaplan-Meier curves were used to analyze overall survival(OS)and progression-free survival(PFS)across groups.Multivariate Cox regression was performed to evaluate prognostic factors,and a nomogram was constructed based on these results.Results:The OS and PFS of single-positive groups for CD38,CD138,CD45,CD56,and CD200 were all shorter than those of their respective single-negative groups(all P<0.05).Significant differences were observed in OS(P<0.001)and PFS(P=0.001)among Groups A,B,and C.Group A had shorter OS and PFS(all P=0.001)compared to the Group B+C(cases from Group B and Group C were combined).CD45 and CD200 double-positive was an independent prognostic factor for NDMM[hazard ratio(HR)=2.178,95%confidence interval(CI)1.048 to 4.529;P=0.037].The nomogram and calibration curves constructed from multivariate Cox regression analysis demonstrated good concordance(concordance index=0.706;95%CI 0.661 to 0.751).Conclusion:NDMM patients with double-positive expression of CD45 and CD200 have significantly shorter OS and PFS.Compared with the use of either marker alone,the combined assessment of CD45 and CD200 may provide better prognostic stratification for MM patients.
基金Supported by Natural Science Foundation of Guangdong Province in China(2018KTSCX161)。
文摘The boundness and compactness of products of multiplication,composition and differentiation on weighted Bergman spaces in the unit ball are studied.We define the differentiation operator on the space of holomorphic functions in the unit ball by radial derivative.Then we extend the Sharma's results.
文摘The charge carrier transport and recombination dynamics in the quantum dots-based light-emitting diodes(QLEDs)featuring multiple emitting layers(M-EMLs)has a great impact on the device performance.In this work,QLEDs based on M-EMLs separated by polyethyleneimine ethoxylated(PEIE)layer with different stacking sequences of blue(B),green(G),and red(R)QDs layer were used to intuitively explore the injection,transportation and recombination processes of the charge carriers in QLEDs by using the time-resolved electroluminescence(TrEL)spectra.From the TrEL spectra mea-surements,green and red emissions were obtained first in the QLEDs with the EMLs sequences of G/PEIE/B/PEIE/R and B/PEIE/R/PEIE/G along the direction of light emission,respectively.While the QLEDs adopt EMLs sequences of B/PEIE/G/PEIE/R,the blue,green and red emissions were obtained nearly at the same time.The above phenomenon can be attributed to different charge carrier transmission and radiation recombination process in the EMLs due to different valence band offsets and conduction band offsets between R-,G-and B-QDs by using different sequences of EMLs.White emission with coordi-nates of(0.31,0.31)and correlated color temperature(CCT)of 5916 K was obtained in the QLEDs with the EMLs se-quences of B/PEIE/G/PEIE/R,which can be attributed to the relative uniform emission of B-,G-and R-QDs due to the effec-tive injection and radiation recombination of charge carriers in each of the EMLs.The above results have great significance for further understanding and improving the performance of QLEDs with M-EMLs.
基金supported in part by the National Natural Science Foundation of China(62173051)the Fundamental Research Funds for the Central Universities(2024CDJCGJ012,2023CDJXY-010)+1 种基金the Chongqing Technology Innovation and Application Development Special Key Project(CSTB2022TIADCUX0015,CSTB2022TIAD-KPX0162)the China Postdoctoral Science Foundation(2024M763865)
文摘Dear Editor,This letter addresses the impulse game problem for a general scope of deterministic,multi-player,nonzero-sum differential games wherein all participants adopt impulse controls.Our objective is to formulate this impulse game problem with the modified objective function including interaction costs among the players in a discontinuous fashion,and subsequently,to derive a verification theorem for identifying the feedback Nash equilibrium strategy.
文摘This paper introduces an optimized planning approach for integrating photovoltaic as distributed generation (PV-DG) into the radial distribution power systems, utilizing exhaustive load flow (ELF), loss sensitivity factor (LSF), genetic algorithms (GA) methods, and numerical method based on LSF. The methodology aims to determine the optimal allocation and sizing of multiple PV-DG to minimize power loss through time series power flow analysis. An approach utilizing continuous sensitivity analysis is developed and inherently leverages power flow and loss equations to compute LSF of all buses in the system towards employing a dynamic PV-DG model for more accurate results. The algorithm uses a numerical grid search method to optimize PV-DG placement in a power distribution system, focusing on minimizing system losses. It combines iterative analysis, sensitivity assessment, and comprehensive visualization to identify and present the optimal PV-DG configurations. The present-ed algorithms are verified through co-simulation framework combining MATLAB and OpenDSS to carry out analysis for 12-bus radial distribution test system. The proposed numerical method is compared with other algorithms, such as ELF, LSF methods, and Genetic Algorithms (GA). Results show that the proposed numerical method performs well in comparison with LSF and ELF solutions.
文摘Multiple evanescent white dot syndrome(MEWDS)is an inflammatory fundus disease primarily affecting the outer retina.It is characterized by transient yellow-white dots on the outer retina.Although the exact pathogenesis remains unclear,the progress in multimodal imaging(MMI)has enhanced our understanding of MEWDS.Most cases of MEWDS are idiopathic,lacking a definite cause,and can spontaneously recover;these are what we term classic MEWDS.Consequently,MEWDS is often referred to as the“common cold of the retina”.Simultaneously,patients with other disorders may present with varying degrees of manifestations similar to MEWDS.The resemblance in clinical or imaging findings can lead to misdiagnosis and inappropriate treatment.These MEWDS-like presentations are actually caused by other systemic or ocular disorders with diverse mechanisms.Thus,they differ from classic MEWDS in certain aspects.Using the keywords“MEWDSlike”and“Secondary MEWDS”,we searched for all relevant studies published in the PubMed database from January 2021 to January 2024.Subsequently,we retrospectively summarized the clinical and imaging characteristics of MEWDS,along with the manifestations in other diseases that resembled those of MEWDS,and compared classic MEWDS with these similar presentations.Based on our review,we classified such similar presentations under other conditions into two categories and summarized their features for differential diagnosis.We recommend paying close attention to patients suspected of having MEWDS,as there may be more serious systemic or ocular disorders that require prompt treatment.
基金supported by grant from the National Natural Science Foundation of China(Grant No.82300231).
文摘Multiple myeloma(MM),one of the most common hemato logical neoplasms worldwide,originates from malignant plasma cells in the bone marrow.MM remains an incurable disease,although continued treatment advancements have markedly increased overall survival.Many patients with MM eventually experience relapse or become treatment-refractory1.Patients with relapsed or refractory multiple myeloma(RRMM)become progressively more challenging to manage and have poor prognosis2.
文摘Active inflammation in“inactive”progressive multiple sclerosis:Traditionally,the distinction between relapsing-remitting multiple sclerosis and progressive multiple sclerosis(PMS)has been framed as an inflammatory versus degenerative dichotomy.This was based on a broad misconception regarding essentially all neurodegenerative conditions,depicting the degenerative process as passive and immune-independent occurring as a late byproduct of active inflammation in the central nervous system(CNS),which is(solely)systemically driven.
基金Private DonationLa Trobe Research Focus AreasMultiple Sclerosis Australia,Grant/Award Number:20-032。
文摘Background:Multiple sclerosis(MS)is a chronic disease of the central nervous system(CNS),exhibiting hallmarks of both inflammation and neurodegeneration and with limited treatment options.The intricate nature of MS pathophysiology and its variable progression pose severe challenges for the development of effective therapies.The experimental autoimmune encephalomyelitis(EAE)MS model,in its most common form,is an aggressive disease,which is not representative of the MS course and offers a limited time window for drug evaluation.This study aimed to generate an attenuated EAE variant,which extends the clinical testing window while preserving the high incidence of the standard EAE model.Methods:Components of the EAE induction protocol were titrated to develop a milder disease profile.In a subsequent drug trial using the MS medication fingolimod hydrochloride(FTY,Gilenya),the new variant was validated under prophylactic and therapeutic treatment regimens.Results:The attenuated EAE variant retains the standard hallmarks of neuroinflammation and,crucially,significantly extends the time frame for clinical drug testing.Unlike the standard variant,where FTY efficacy could only be demonstrated by prophylactic treatment,the attenuated variant facilitated differentiation of drug effects by therapeutic treatment initiated early in the acute phase of disease.Conclusion:The new EAE variant is suitable for use in preclinical assessment of candidate therapeutics and the identification of targetable molecular mechanisms underpinning disease development and progression.This study illustrates the importance of optimizing and refining the experimental tool to enhance the translational success of the candidate therapeutics for MS.
基金Supported by Jinhua City Science and Technology Plan Projects,No.2022-4-145.
文摘BACKGROUND Metachronous multiple esophageal squamous cell carcinomas(ESCCs)may occur in some patients after endoscopic resection.Multiple dysplastic lesions in the esophagus increase risk of multiple squamous cell carcinomas(SCCs).Endoscopic imaging technology such as narrow band imaging(NBI),can detect early SCC.Lugol chromoendoscopy is also the conventional standard technique for detecting superficial ESCC.However,little is known about the interval from the first SCC to the metachronous SCC.Effective methods to prevent multiple metachronous SCCs are needed in survivors of esophageal SCC.CASE SUMMARY A 56-year-old man showed a slightly elevated reddish area in the middle thoracic esophagus at 30 cm from the incisors on gastroscopy for routine examination.Esophageal mucosa lesion was about 2.5 cm.NBI and magnifying gastroscopy confirmed intra-epithelial papillary loop type B-1 according to the Japan Esophageal Society Classification.Lugol chromoendoscopy was used to evaluate the dysplastic squamous epithelium in the esophagus.Biopsy pathology revealed severe dysplastic squamous epithelium.Computed tomography showed no lymph node metastasis.His complete blood test and tumor markers were within reference values.He had no history of alcohol consumption and smoking.Mucosal lesion was dissected by endoscopic submucosal dissection(ESD).Postoperative pathological results showed moderately differentiated squamous carcinoma.No cancer thrombus was seen in the vasculature,and the surrounding cut edge was not involved.The patient underwent radiotherapy within 2 months after ESD.The multiple Lugol-voiding lesions disappeared,and enhanced chest computed tomography revealed no lymph node metastasis.CONCLUSION This is the first case of multiple dysplastic lesions of esophagus cured by radiotherapy.Radiotherapy after minimally invasive endoscopic treatment might be a safe and effective optional therapeutic strategy to prevent metachronous multiple esophageal SCCs.
