Testing of large-sized specimens is becoming increasingly important in deep underground rock mechanics and engineering.In traditional mechanical loading,stresses on large-sized specimens are achieved by large host fra...Testing of large-sized specimens is becoming increasingly important in deep underground rock mechanics and engineering.In traditional mechanical loading,stresses on large-sized specimens are achieved by large host frames and hydraulic pumps,which could lead to great investment.Low-cost testing machines clearly always have great appeal.In this study,a new approach is proposed using thermal expansion stress to load rock specimens,which may be particularly suitable for tests of deep hot dry rock with high temperatures.This is a different technical route from traditional mechanical loading through hydraulic pressure.For the rock mechanics test system of hot dry rock that already has an investment in heating systems,this technology may reduce the cost of the loading subsystem by fully utilizing the temperature changes.This paper presents the basic principle and a typical design of this technical solution.Preliminary feasibility analysis is then conducted based on numerical simulations.Although some technical details still need to be resolved,the feasibility of this loading approach has been preliminarily confirmed.展开更多
Liver cancer remains a leading cause of mortality worldwide,and precise diagnostic tools are essential for effective treatment planning.Liver Tumors(LTs)vary significantly in size,shape,and location,and can present wi...Liver cancer remains a leading cause of mortality worldwide,and precise diagnostic tools are essential for effective treatment planning.Liver Tumors(LTs)vary significantly in size,shape,and location,and can present with tissues of similar intensities,making automatically segmenting and classifying LTs from abdominal tomography images crucial and challenging.This review examines recent advancements in Liver Segmentation(LS)and Tumor Segmentation(TS)algorithms,highlighting their strengths and limitations regarding precision,automation,and resilience.Performance metrics are utilized to assess key detection algorithms and analytical methods,emphasizing their effectiveness and relevance in clinical contexts.The review also addresses ongoing challenges in liver tumor segmentation and identification,such as managing high variability in patient data and ensuring robustness across different imaging conditions.It suggests directions for future research,with insights into technological advancements that can enhance surgical planning and diagnostic accuracy by comparing popular methods.This paper contributes to a comprehensive understanding of current liver tumor detection techniques,provides a roadmap for future innovations,and improves diagnostic and therapeutic outcomes for liver cancer by integrating recent progress with remaining challenges.展开更多
BACKGROUND Urinary system tumors often cause negative psychological symptoms,such as depression and dysphoria which significantly impact immune function and indirectly affect cancer prognosis.While epirubicin(EPI)is r...BACKGROUND Urinary system tumors often cause negative psychological symptoms,such as depression and dysphoria which significantly impact immune function and indirectly affect cancer prognosis.While epirubicin(EPI)is recommended by the European Association of Urology and can improve prognosis,its long-term use can cause toxic side effects,reduce treatment compliance,and increase psycho-logical burden.Therefore,an appropriate intervention mode is necessary.METHODS This was a retrospective study including 110 patients with urinary system tumors and depression admitted to Zhumadian Central Hospital between March 2021 and July 2023.Patients were divided into conventional(n=55)and joint inter-vention(n=55)groups.The conventional group received mitomycin and routine nursing,while the joint intervention group received EPI and mindfulness intervention.Both groups underwent three cycles of chemotherapy.Immune function(CD4+cells,CD8+cells,CD4+/CD8+ratio),tumor marker levels[urinary bladder cancer antigen(UBC),bladder tumor antigen(BTA)and nuclear matrix protein 22(NMP22)],quality of life questionnaire-core 30(QLQ-C30),17-item Hamilton depression scale(HAMD-17),and cancer-related fatigue[cancer fatigue scale(CFS)]were assessed.Adverse reactions and nursing satisfaction were recorded and evaluated.RESULTS Post-intervention,CD4+,CD8+,and CD4+/CD8+levels increased in both groups,with the joint intervention group showing more significant improvement(P<0.05).Tumor marker levels(NMP22,BTA,and UBC)were lower in the joint intervention group compared to the conventional group(P<0.05).The joint intervention group also showed a greater reduction in HAMD-17 scores(9.38±3.12 vs 15.45±4.86,P<0.05),higher QLQ-C30 scores,and lower CFS scores(both P<0.05).Additionally,the joint intervention group had a lower incidence of adverse reactions and higher nursing satisfaction(P<0.05).CONCLUSION EPI combined with mindfulness intervention significantly improved clinical outcomes in patients with urinary system tumors and depression and is worthy of clinical application.展开更多
BACKGROUND In recent years,numerous reports have been published regarding the relationship between the gut microbiota and the tumor immune microenvironment(TIME).However,to date,no systematic study has been conducted ...BACKGROUND In recent years,numerous reports have been published regarding the relationship between the gut microbiota and the tumor immune microenvironment(TIME).However,to date,no systematic study has been conducted on the relationship between gut microbiota and the TIME using bibliometric methods.AIM To describe the current global research status on the correlation between gut microbiota and the TIME,and to identify the most influential countries,research institutions,researchers,and research hotspots related to this topic.METHODS We searched for all literature related to gut microbiota and TIME published from January 1,2014,to May 28,2024,in the Web of Science Core Collection database.We then conducted a bibliometric analysis and created visual maps of the published literature on countries,institutions,authors,keywords,references,etc.,using CiteSpace(6.2R6),VOSviewer(1.6.20),and bibliometrics(based on R 4.3.2).RESULTS In total,491 documents were included,with a rapid increase in the number of publications starting in 2019.The country with the highest number of publications was China,followed by the United States.Germany has the highest number of citations in literature.From a centrality perspective,the United States has the highest influence in this field.The institutions with the highest number of publications were Shanghai Jiao Tong University and Zhejiang University.However,the institution with the most citations was the United States National Cancer Institute.Among authors,Professor Giorgio Trinchieri from the National Institutes of Health has the most local impact in this field.The most cited author was Fan XZ.The results of journal publications showed that the top three journals with the highest number of published papers were Frontiers in Immunology,Cancers,and Frontiers in Oncology.The three most frequently used keywords were gut microbiota,tumor microenvironment,and immunotherapy.CONCLUSION This study systematically elaborates on the research progress related to gut microbiota and TIME over the past decade.Research results indicate that the number of publications has rapidly increased since 2019,with research hotspots including“gut microbiota”,“tumor microenvironment”and“immunotherapy”.Exploring the effects of specific gut microbiota or derived metabolites on the behavior of immune cells in the TIME,regulating the secretion of immune molecules,and influencing immunotherapy are research hotspots and future research directions.展开更多
Pediatric pancreatic tumors,though rare,pose significant diagnostic and manage-ment challenges.The recent,22-year nationwide survey on pediatric pancreatic tumors in Japan by Makita et al offers valuable insights into...Pediatric pancreatic tumors,though rare,pose significant diagnostic and manage-ment challenges.The recent,22-year nationwide survey on pediatric pancreatic tumors in Japan by Makita et al offers valuable insights into this uncommon enti-ty,revealing striking geographical variations and questioning current treatment paradigms.This editorial commentary analyzes the study's key findings,inclu-ding the predominance of solid pseudopapillary neoplasms and their younger age of onset,which contrast sharply with Western data.It explores the implications for clinical practice and research,emphasizing the need for population-specific approaches to diagnosis and treatment.The revealed limited institutional expe-rience and surgical management patterns prompt a reevaluation of optimal care delivery for these complex cases,suggesting benefits of centralizing healthcare services.Furthermore,the commentary advocates for international collaborative studies to elucidate the genetic,environmental,and lifestyle factors influencing the development and progression of pediatric pancreatic tumors across diverse populations.It also outlines future directions,calling for advancements in precision medicine and innovative care delivery models to improve global patient outcomes.Unraveling Makita et al's findings within the broader landscape of pediatric oncology can stimulate further research and clinical advancements in managing pancreatic and other rare tumors in children.展开更多
Based on the analysis of the basic characteristics of medium-and large-sized marine gas fields in Sichuan Basin, combined with the division of major reservoir forming geological units in the marine craton stage and th...Based on the analysis of the basic characteristics of medium-and large-sized marine gas fields in Sichuan Basin, combined with the division of major reservoir forming geological units in the marine craton stage and their control on key hydrocarbon accumulation factors, the distribution law of medium-and large-sized marine carbonate gas fields in the basin was examined and the exploration direction was pointed out. Through the analysis of the periodic stretching-uplifting background, it is concluded that five large scale paleo-rifts, three large scale paleo-uplifts, five large scale paleo erosion surfaces were formed in the marine craton stage of Sichuan Basin, and these geological units control the key reservoir forming factors of medium and large sized gas fields:(1) Large-scale paleo-rifts control the distribution of high-quality hydrocarbon generation centers.(2) The margin of large-scale paleo-rifts, high position of paleo-uplifts and paleo erosion surfaces control the distribution of high-quality reservoirs.(3) Large-scale paleo-rifts, paleo-uplifts, paleo erosion surfaces and present tectonic setting jointly control the formation of many types of large and medium-sized traps.(4) Natural gas accumulation is controlled by the inheritance evolution of traps in large geological units. Based on the comparative analysis of the distribution characteristics of medium-and large-sized gas fields and large geological units, it is proposed that the superimposition relationship between single or multiple geological units and the present structure controls the distribution of medium-and large-sized gas fields, and the "three paleo" superimposed area is the most advantageous. According to the above rules, the main exploration fields and directions of medium-and large-sized marine carbonate gas fields in Sichuan Basin include periphery of Deyang-Anyue paleo-rift, eastern margin of Longmenshan paleo-rift, margins of Kaijiang-Liangping oceanic trough and Chengkou-western Hubei oceanic trough, the high part of the subaqueous paleo-uplifts around Central Sichuan, paleo erosion surfaces of the top boundary of Maokou Formation in eastern and southern Sichuan Basin, paleo erosion surfaces of the top boundary of the Leikoupo Formation in central and western Sichuan Basin.展开更多
When heavy machines and large scaled receiver system of communication equipment are manufactured, it always needs to produce large-sized steel castings, aluminum castings and etc. Some defects of hot cracking by therm...When heavy machines and large scaled receiver system of communication equipment are manufactured, it always needs to produce large-sized steel castings, aluminum castings and etc. Some defects of hot cracking by thermal stress often appear during solidification process as these castings are produced, which results in failure of castings. Therefore predicting the effects of technological parameters for production of castings on the thermal stress during solidification process becomes an important means. In this paper, the mathematical models have been established and numerical calculation of temperature fields by using finite difference method (FDM) and then thermal stress fields by using finite element method (FEM) during solidification process of castings have been carried out. The technological parameters of production have been optimized by the results of calculation and the defects of hot cracking have been eliminated. Modeling and simulation of 3D thermal stress during solidification processes of large-sized castings provided a scientific basis, which promoted further development of advanced manufacturing technique.展开更多
Recently, research strives to apply Ultra High Performance Concrete (UHPC) to large-sized structures owing to its remarkable mechanical performance and durability compared to normal concrete. The Korea Institute of Co...Recently, research strives to apply Ultra High Performance Concrete (UHPC) to large-sized structures owing to its remarkable mechanical performance and durability compared to normal concrete. The Korea Institute of Construction Technology proposed SuperBridge800, an edge girder type UHPC cable stayed bridge with central span of 800 m, through its detailed design. The bridge is designed to be erected through the connection of precast UHPC segments. The precast UHPC segment is monolithically composed of one ribbed deck slab and edge girders at each side. The connection between the precast segments is achieved by steel bars at the edge girders and by UHPC cast-in-place wet joint at the slab. Despite of the outstanding mechanical performance of UHPC, the fabrication of large-sized members is a difficult task since UHPC hardens faster than normal concrete and requires a special curing process. Therefore, the constructability of large-sized UHPC segment should be secured to achieve SuperBridge800. Besides, the performance of the connection between segments should also be guaranteed, especially in terms of the fatigue performance of the UHPC cast-in-place joint, which constitutes a weak point. To that goal, two half-scaled UHPC segments are manufactured and the constructability is examined by fabricating a large-sized UHPC member connected with respect to the design conditions. This study conducts rolling fatigue test on the so-fabricated large-sized UHPC member. Rolling fatigue test is carried out up to 2 million cycles considering actual vehicle load at each center and quarter points of the member. The test results confirm that the service limit state is satisfied.展开更多
Large-sized aluminum tube has big section effect, aspect ratio and thin thickness, so that the extrusion technology is complex and the large specific pressure is generated in extrusion cavity. The temperature variatio...Large-sized aluminum tube has big section effect, aspect ratio and thin thickness, so that the extrusion technology is complex and the large specific pressure is generated in extrusion cavity. The temperature variation and velocity effect is difficult to control. The extrusion forming of large-sized aluminum tube was researched and simulated. Three-dimensional thermo-mechanical coupled finite element model was constructed and appropriate boundary conditions were given out. The results show that large-sized aluminum tube can be formed by isothermal extrusion through controlling the extrusion velocity and founding the relationship between extrusion velocity and extrusion temperature.展开更多
Background:Despite advances in the diagnosis of patients with hepatocellular carcinoma(HCC),70%-80%of patients are diagnosed with advanced stage disease.Portal vein tumor thrombus(PVTT)is among the most ominous signs ...Background:Despite advances in the diagnosis of patients with hepatocellular carcinoma(HCC),70%-80%of patients are diagnosed with advanced stage disease.Portal vein tumor thrombus(PVTT)is among the most ominous signs of advanced stage disease and has been associated with poor survival if untreated.Data sources:A systematic search of MEDLINE(PubMed),Embase,Cochrane Library and Database for Systematic Reviews(CDSR),Google Scholar,and National Institute for Health and Clinical Excellence(NICE)databases until December 2022 was conducted using free text and MeSH terms:hepatocellular carcinoma,portal vein tumor thrombus,portal vein thrombosis,vascular invasion,liver and/or hepatic resection,liver transplantation,and systematic review.Results:Centers of surgical excellence have reported promising results related to the individualized surgical management of portal thrombus versus arterial chemoembolization or systemic chemotherapy.Critical elements to the individualized surgical management of HCC and portal thrombus include precise classification of the portal vein tumor thrombus,accurate identification of the subgroups of patients who may benefit from resection,as well as meticulous surgical technique.This review addressed five specific areas:(a)formation of PVTT;(b)classifications of PVTT;(c)controversies related to clinical guidelines;(d)surgical treatments versus non-surgical approaches;and(e)characterization of surgical techniques correlated with classifications of PVTT.Conclusions:Current evidence from Chinese and Japanese high-volume centers demonstrated that patients with HCC and associated PVTT can be managed with surgical resection with acceptable results.展开更多
BACKGROUND Tumor budding(TB)has emerged as a promising independent prognostic biomarker in colorectal cancer(CRC).The prognostic role of TB has been extensively studied and currently affects clinical decision making i...BACKGROUND Tumor budding(TB)has emerged as a promising independent prognostic biomarker in colorectal cancer(CRC).The prognostic role of TB has been extensively studied and currently affects clinical decision making in patients with stage I and II CRC.However,existing prognostic studies on TB in stage III CRC have been confined to small retrospective cohort studies.Consequently,this study investigated the correlation among TB categories,clinicopathological features,and prognosis in stage III-IV CRC to further enhance the precision and individualization of treatment through refined prognostic risk stratification.AIM To analyze the relationship between TB categories and clinicopathological characteristics and assess their prognostic value in stage III-IV CRC to further refine the prognostic risk stratification of stage III-IV CRC.METHODS The clinical data of 547 CRC patients were collected for this retrospective study.Infiltration at the front edge of the tumor buds was counted according to the 2016 International Tumor Budding Consensus Conference guidelines.RESULTS Multivariate Cox proportional hazards regression analysis demonstrated that chemotherapy(P=0.004),clinical stage IV(P<0.001),≥4 regional lymph node metastases(P=0.004),left-sided colonic cancer(P=0.040),and Bd 2-3(P=0.002)were independent prognostic factors in patients with stage III-IV CRC.Moreover,the density of tumor infiltrating lymphocytes was higher in Bd 1 than in Bd 2-3,both in the tumor stroma and its invasive margin.CONCLUSION TB has an independent predictive prognostic value in patients with stage III-IV CRC.It is recommended to complete the TB report of stage III-IV CRC cases in the standardized pathological report to further refine risk stratification.展开更多
BACKGROUND Calculus bovis(CB),used in traditional Chinese medicine,exhibits anti-tumor effects in various cancer models.It also constitutes an integral component of a compound formulation known as Pien Tze Huang,which...BACKGROUND Calculus bovis(CB),used in traditional Chinese medicine,exhibits anti-tumor effects in various cancer models.It also constitutes an integral component of a compound formulation known as Pien Tze Huang,which is indicated for the treatment of liver cancer.However,its impact on the liver cancer tumor microenvironment,particularly on tumor-associated macrophages(TAMs),is not well understood.AIM To elucidate the anti-liver cancer effect of CB by inhibiting M2-TAM polarization via Wnt/β-catenin pathway modulation.METHODS This study identified the active components of CB using UPLC-Q-TOF-MS,evaluated its anti-neoplastic effects in a nude mouse model,and elucidated the underlying mechanisms via network pharmacology,transcriptomics,and molecular docking.In vitro assays were used to investigate the effects of CB-containing serum on HepG2 cells and M2-TAMs,and Wnt pathway modulation was validated by real-time reverse transcriptase-polymerase chain reaction and Western blot analysis.RESULTS This study identified 22 active components in CB,11 of which were detected in the bloodstream.Preclinical investigations have demonstrated the ability of CB to effectively inhibit liver tumor growth.An integrated approach employing network pharmacology,transcriptomics,and molecular docking implicated the Wnt signaling pathway as a target of the antineoplastic activity of CB by suppressing M2-TAM polarization.In vitro and in vivo experiments further confirmed that CB significantly hinders M2-TAM polarization and suppresses Wnt/β-catenin pathway activation.The inhibitory effect of CB on M2-TAMs was reversed when treated with the Wnt agonist SKL2001,confirming its pathway specificity.CONCLUSION This study demonstrated that CB mediates inhibition of M2-TAM polarization through the Wnt/β-catenin pathway,contributing to the suppression of liver cancer growth.展开更多
BACKGROUND Pediatric pancreatic tumors are rare and account for<0.1%of all childhood cancers.The primary treatment for pancreatic tumors is surgical resection.However,because of the lack of knowledge regarding pedi...BACKGROUND Pediatric pancreatic tumors are rare and account for<0.1%of all childhood cancers.The primary treatment for pancreatic tumors is surgical resection.However,because of the lack of knowledge regarding pediatric pancreatic tumors,no comprehensive treatment plans for pediatric pancreatic tumors have been developed.AIM To compared the clinical features,treatment methods,and prognosis of pediatric pancreatic tumors in Japan with those in other countries.METHODS Questionnaires were sent to 213 pediatric surgical units in Japan.Pancreatic tumors that were not surgically treated were excluded from the survey.The primary survey investigated the number of patients aged 0-18 years who underwent pancreatic tumor surgery and the type of tumors managed during the 22-year study period(from January 1,2000 to December 31,2021)by post card.The secondary survey assessed the clinical images,treatment methods,and tumor outcomes via email.RESULTS The primary survey enrolled 228 patients.In the secondary survey,213 patients were eventually enrolled.The most common type of pancreatic tumor was solid pseudopapillary neoplasm(SPN)[n=164(77.0%)],followed by pancreatoblastoma[n=16(7.5%)],pancreatic endocrine tumor[n=14(6.6%)],non-epithelial tumor[n=9(4.2%)],pancreatic tumor[n=7(3.3%)],and metastatic pancreatic tumor[n=3(1.4%)].Overall,123(57.7%)patients underwent distal pancreatectomy,of whom 49 underwent laparoscopic surgery.Forty-four(20.7%)patients underwent enucleation,of whom eight underwent laparoscopic surgery.Thirty-two(15.0%)patients underwent pancreaticoduodenectomy,of whom one underwent laparoscopic surgery.All patients with SPN,including those with distant metastases and recurrent disease,survived.CONCLUSION SPN was more common in Japan than in other countries.Regardless of the histological type,resection is the most effective treatment for pediatric pancreatic tumors.展开更多
Simulation technique is an efficient approach to realize the planning and scheduling of manufacturing process of products. An appropriate and efficient manufacturing process model is the basis and key of manufacturing...Simulation technique is an efficient approach to realize the planning and scheduling of manufacturing process of products. An appropriate and efficient manufacturing process model is the basis and key of manufacturing process simulation. By analyzing the features of large-sized and complex products, a method of manufacturing process modeling based on activity network is presented and a mapping algorithm of translating BOM/BOP into the manufacturing process model is designed in detail.展开更多
BACKGROUND Most patients with advanced pancreatic neuroendocrine tumors(pNETs)die due to tumor progression.Therefore,identifying new therapies with low toxicity and good tolerability to use concomitantly with the esta...BACKGROUND Most patients with advanced pancreatic neuroendocrine tumors(pNETs)die due to tumor progression.Therefore,identifying new therapies with low toxicity and good tolerability to use concomitantly with the established pNET treatment is relevant.In this perspective,metformin is emerging as a molecule of interest.Retrospective studies have described metformin,a widely used agent for the treatment of patients with type 2 diabetes mellitus(T2DM),to be effective in modulating different tumor-related events,including cancer incidence,recurrence and survival by inhibiting mTOR phosphorylation.This systematic review evaluates the role of T2DM and metformin in the insurgence and post-treatment outcomes in patients with pNET.AIM To systematically analyze and summarize evidence related to the diagnostic and prognostic value of T2DM and metformin for predicting the insurgence and posttreatment outcomes of pNET.METHODS A systematic review of the published literature was undertaken,focusing on the role of T2DM and metformin in insurgence and prognosis of pNET,measured through outcomes of tumor-free survival(TFS),overall survival and progression free survival.RESULTS A total of 13 studies(5674 patients)were included in this review.Analysis of 809 pNET cases from five retrospective studies(low study heterogeneity with I^(2)=0%)confirms the correlation between T2DM and insurgence of pNET(OR=2.13,95%CI=1.56-4.55;P<0.001).The pooled data from 1174 pNET patients showed the correlation between T2DM and post-treatment TFS in pNET patients(hazard ratio=1.84,95%CI=0.78-2.90;P<0.001).The study heterogeneity was intermediate,with I^(2)=51%.A few studies limited the possibility of performing pooled analysis in the setting of metformin;therefore,results were heterogeneous,with no statistical relevance to the use of this drug in the diagnosis and prognosis of pNET.CONCLUSION T2DM represents a risk factor for the insurgence of pNET and is a significant predictor of poor post-treatment TFS of pNET patients.Unfortunately,a few studies with heterogeneous results limited the possibility of exploring the effect of metformin in the diagnosis and prognosis of pNET.展开更多
Throughout tumorigenesis, the co-evolution of tumor cells and their surrounding microenvironment leads to the development of malignant phenotypes. Cellular communication within the tumor microenvironment(TME) plays a ...Throughout tumorigenesis, the co-evolution of tumor cells and their surrounding microenvironment leads to the development of malignant phenotypes. Cellular communication within the tumor microenvironment(TME) plays a critical role in influencing various aspects of tumor progression, including invasion and metastasis. The release of exosomes, a type of extracellular vesicle, by most cell types in the body, is an essential mediator of intercellular communication. A growing body of research indicates that tumor-derived exosomes(TDEs) significantly expedite tumor progression through multiple mechanisms, inducing epithelial-mesenchymal transition and macrophage polarization, enhancing angiogenesis, and aiding in the immune evasion of tumor cells. Herein, we describe the formation and characteristics of the TME, and summarize the contents of TDEs and their diverse functions in modulating tumor development. Furthermore, we explore potential applications of TDEs in tumor diagnosis and treatment.展开更多
Despite significant advances in our understanding of the molecular pathogenesis of liver cancer and the availability of novel pharmacotherapies,liver cancer remains the fourth leading cause of cancer-related mortality...Despite significant advances in our understanding of the molecular pathogenesis of liver cancer and the availability of novel pharmacotherapies,liver cancer remains the fourth leading cause of cancer-related mortality worldwide.Tumor relapse,resistance to current anti-cancer drugs,metastasis,and organ toxicity are the major challenges that prevent considerable improvements in patient survival and quality of life.Calculus bovis(CB),an ancient Chinese medicinal drug,has been used to treat various pathologies,including stroke,convulsion,epilepsy,pain,and cancer.In this editorial,we discuss the research findings recently published by Huang et al on the therapeutic effects of CB in inhibiting the development of liver cancer.Utilizing the comprehensive transcriptomic analyses,in vitro experiments,and in vivo studies,the authors demonstrated that CB treatment inhibits the tumor-promoting M2 phenotype of tumor-associated macrophages via downregulating Wnt pathway.While multiple studies have been performed to explore the molecular mechanisms regulated by CB,this study uniquely shows its role in modulating the M2 phenotype of macrophages present within the tumor microenvironment.This study opens new avenues of future investigations aimed at investigating this drug’s efficacy in various mouse models including the effects of combination therapy,and against drug-resistant tumors.展开更多
Subarachnoid hemorrhage is associated with high morbidity and mortality and lacks effective treatment.Pyroptosis is a crucial mechanism underlying early brain injury after subarachnoid hemorrhage.Previous studies have...Subarachnoid hemorrhage is associated with high morbidity and mortality and lacks effective treatment.Pyroptosis is a crucial mechanism underlying early brain injury after subarachnoid hemorrhage.Previous studies have confirmed that tumor necrosis factor-stimulated gene-6(TSG-6)can exert a neuroprotective effect by suppressing oxidative stress and apoptosis.However,no study to date has explored whether TSG-6 can alleviate pyroptosis in early brain injury after subarachnoid hemorrhage.In this study,a C57BL/6J mouse model of subarachnoid hemorrhage was established using the endovascular perforation method.Our results indicated that TSG-6 expression was predominantly detected in astrocytes,along with NLRC4 and gasdermin-D(GSDMD).The expression of NLRC4,GSDMD and its N-terminal domain(GSDMD-N),and cleaved caspase-1 was significantly enhanced after subarachnoid hemorrhage and accompanied by brain edema and neurological impairment.To explore how TSG-6 affects pyroptosis during early brain injury after subarachnoid hemorrhage,recombinant human TSG-6 or a siRNA targeting TSG-6 was injected into the cerebral ventricles.Exogenous TSG-6 administration downregulated the expression of NLRC4 and pyroptosis-associated proteins and alleviated brain edema and neurological deficits.Moreover,TSG-6 knockdown further increased the expression of NLRC4,which was accompanied by more severe astrocyte pyroptosis.In summary,our study revealed that TSG-6 provides neuroprotection against early brain injury after subarachnoid hemorrhage by suppressing NLRC4 inflammasome activation-induced astrocyte pyroptosis.展开更多
基金National Natural Science Foundation of ChinaGrant/Award Number:41972316+3 种基金Sichuan Science&Technology FoundationGrant/Award Number:2022YFSY0007Joint Funds of the National Natural Science Foundation of ChinaGrant/Award Number:U2344226。
文摘Testing of large-sized specimens is becoming increasingly important in deep underground rock mechanics and engineering.In traditional mechanical loading,stresses on large-sized specimens are achieved by large host frames and hydraulic pumps,which could lead to great investment.Low-cost testing machines clearly always have great appeal.In this study,a new approach is proposed using thermal expansion stress to load rock specimens,which may be particularly suitable for tests of deep hot dry rock with high temperatures.This is a different technical route from traditional mechanical loading through hydraulic pressure.For the rock mechanics test system of hot dry rock that already has an investment in heating systems,this technology may reduce the cost of the loading subsystem by fully utilizing the temperature changes.This paper presents the basic principle and a typical design of this technical solution.Preliminary feasibility analysis is then conducted based on numerical simulations.Although some technical details still need to be resolved,the feasibility of this loading approach has been preliminarily confirmed.
基金the“Intelligent Recognition Industry Service Center”as part of the Featured Areas Research Center Program under the Higher Education Sprout Project by the Ministry of Education(MOE)in Taiwan,and the National Science and Technology Council,Taiwan,under grants 113-2221-E-224-041 and 113-2622-E-224-002.Additionally,partial support was provided by Isuzu Optics Corporation.
文摘Liver cancer remains a leading cause of mortality worldwide,and precise diagnostic tools are essential for effective treatment planning.Liver Tumors(LTs)vary significantly in size,shape,and location,and can present with tissues of similar intensities,making automatically segmenting and classifying LTs from abdominal tomography images crucial and challenging.This review examines recent advancements in Liver Segmentation(LS)and Tumor Segmentation(TS)algorithms,highlighting their strengths and limitations regarding precision,automation,and resilience.Performance metrics are utilized to assess key detection algorithms and analytical methods,emphasizing their effectiveness and relevance in clinical contexts.The review also addresses ongoing challenges in liver tumor segmentation and identification,such as managing high variability in patient data and ensuring robustness across different imaging conditions.It suggests directions for future research,with insights into technological advancements that can enhance surgical planning and diagnostic accuracy by comparing popular methods.This paper contributes to a comprehensive understanding of current liver tumor detection techniques,provides a roadmap for future innovations,and improves diagnostic and therapeutic outcomes for liver cancer by integrating recent progress with remaining challenges.
文摘BACKGROUND Urinary system tumors often cause negative psychological symptoms,such as depression and dysphoria which significantly impact immune function and indirectly affect cancer prognosis.While epirubicin(EPI)is recommended by the European Association of Urology and can improve prognosis,its long-term use can cause toxic side effects,reduce treatment compliance,and increase psycho-logical burden.Therefore,an appropriate intervention mode is necessary.METHODS This was a retrospective study including 110 patients with urinary system tumors and depression admitted to Zhumadian Central Hospital between March 2021 and July 2023.Patients were divided into conventional(n=55)and joint inter-vention(n=55)groups.The conventional group received mitomycin and routine nursing,while the joint intervention group received EPI and mindfulness intervention.Both groups underwent three cycles of chemotherapy.Immune function(CD4+cells,CD8+cells,CD4+/CD8+ratio),tumor marker levels[urinary bladder cancer antigen(UBC),bladder tumor antigen(BTA)and nuclear matrix protein 22(NMP22)],quality of life questionnaire-core 30(QLQ-C30),17-item Hamilton depression scale(HAMD-17),and cancer-related fatigue[cancer fatigue scale(CFS)]were assessed.Adverse reactions and nursing satisfaction were recorded and evaluated.RESULTS Post-intervention,CD4+,CD8+,and CD4+/CD8+levels increased in both groups,with the joint intervention group showing more significant improvement(P<0.05).Tumor marker levels(NMP22,BTA,and UBC)were lower in the joint intervention group compared to the conventional group(P<0.05).The joint intervention group also showed a greater reduction in HAMD-17 scores(9.38±3.12 vs 15.45±4.86,P<0.05),higher QLQ-C30 scores,and lower CFS scores(both P<0.05).Additionally,the joint intervention group had a lower incidence of adverse reactions and higher nursing satisfaction(P<0.05).CONCLUSION EPI combined with mindfulness intervention significantly improved clinical outcomes in patients with urinary system tumors and depression and is worthy of clinical application.
基金Supported by the Shanghai Science and Technology Commission Project,No.21010504300Shanghai Jiading District Traditional Chinese Medicine Key Specialty Construction Project,No.2020-JDZYYZDZK-01.
文摘BACKGROUND In recent years,numerous reports have been published regarding the relationship between the gut microbiota and the tumor immune microenvironment(TIME).However,to date,no systematic study has been conducted on the relationship between gut microbiota and the TIME using bibliometric methods.AIM To describe the current global research status on the correlation between gut microbiota and the TIME,and to identify the most influential countries,research institutions,researchers,and research hotspots related to this topic.METHODS We searched for all literature related to gut microbiota and TIME published from January 1,2014,to May 28,2024,in the Web of Science Core Collection database.We then conducted a bibliometric analysis and created visual maps of the published literature on countries,institutions,authors,keywords,references,etc.,using CiteSpace(6.2R6),VOSviewer(1.6.20),and bibliometrics(based on R 4.3.2).RESULTS In total,491 documents were included,with a rapid increase in the number of publications starting in 2019.The country with the highest number of publications was China,followed by the United States.Germany has the highest number of citations in literature.From a centrality perspective,the United States has the highest influence in this field.The institutions with the highest number of publications were Shanghai Jiao Tong University and Zhejiang University.However,the institution with the most citations was the United States National Cancer Institute.Among authors,Professor Giorgio Trinchieri from the National Institutes of Health has the most local impact in this field.The most cited author was Fan XZ.The results of journal publications showed that the top three journals with the highest number of published papers were Frontiers in Immunology,Cancers,and Frontiers in Oncology.The three most frequently used keywords were gut microbiota,tumor microenvironment,and immunotherapy.CONCLUSION This study systematically elaborates on the research progress related to gut microbiota and TIME over the past decade.Research results indicate that the number of publications has rapidly increased since 2019,with research hotspots including“gut microbiota”,“tumor microenvironment”and“immunotherapy”.Exploring the effects of specific gut microbiota or derived metabolites on the behavior of immune cells in the TIME,regulating the secretion of immune molecules,and influencing immunotherapy are research hotspots and future research directions.
文摘Pediatric pancreatic tumors,though rare,pose significant diagnostic and manage-ment challenges.The recent,22-year nationwide survey on pediatric pancreatic tumors in Japan by Makita et al offers valuable insights into this uncommon enti-ty,revealing striking geographical variations and questioning current treatment paradigms.This editorial commentary analyzes the study's key findings,inclu-ding the predominance of solid pseudopapillary neoplasms and their younger age of onset,which contrast sharply with Western data.It explores the implications for clinical practice and research,emphasizing the need for population-specific approaches to diagnosis and treatment.The revealed limited institutional expe-rience and surgical management patterns prompt a reevaluation of optimal care delivery for these complex cases,suggesting benefits of centralizing healthcare services.Furthermore,the commentary advocates for international collaborative studies to elucidate the genetic,environmental,and lifestyle factors influencing the development and progression of pediatric pancreatic tumors across diverse populations.It also outlines future directions,calling for advancements in precision medicine and innovative care delivery models to improve global patient outcomes.Unraveling Makita et al's findings within the broader landscape of pediatric oncology can stimulate further research and clinical advancements in managing pancreatic and other rare tumors in children.
基金Supported by the China National Science and Technology Major Project(2016ZX05007004,2016ZX05004005)
文摘Based on the analysis of the basic characteristics of medium-and large-sized marine gas fields in Sichuan Basin, combined with the division of major reservoir forming geological units in the marine craton stage and their control on key hydrocarbon accumulation factors, the distribution law of medium-and large-sized marine carbonate gas fields in the basin was examined and the exploration direction was pointed out. Through the analysis of the periodic stretching-uplifting background, it is concluded that five large scale paleo-rifts, three large scale paleo-uplifts, five large scale paleo erosion surfaces were formed in the marine craton stage of Sichuan Basin, and these geological units control the key reservoir forming factors of medium and large sized gas fields:(1) Large-scale paleo-rifts control the distribution of high-quality hydrocarbon generation centers.(2) The margin of large-scale paleo-rifts, high position of paleo-uplifts and paleo erosion surfaces control the distribution of high-quality reservoirs.(3) Large-scale paleo-rifts, paleo-uplifts, paleo erosion surfaces and present tectonic setting jointly control the formation of many types of large and medium-sized traps.(4) Natural gas accumulation is controlled by the inheritance evolution of traps in large geological units. Based on the comparative analysis of the distribution characteristics of medium-and large-sized gas fields and large geological units, it is proposed that the superimposition relationship between single or multiple geological units and the present structure controls the distribution of medium-and large-sized gas fields, and the "three paleo" superimposed area is the most advantageous. According to the above rules, the main exploration fields and directions of medium-and large-sized marine carbonate gas fields in Sichuan Basin include periphery of Deyang-Anyue paleo-rift, eastern margin of Longmenshan paleo-rift, margins of Kaijiang-Liangping oceanic trough and Chengkou-western Hubei oceanic trough, the high part of the subaqueous paleo-uplifts around Central Sichuan, paleo erosion surfaces of the top boundary of Maokou Formation in eastern and southern Sichuan Basin, paleo erosion surfaces of the top boundary of the Leikoupo Formation in central and western Sichuan Basin.
文摘When heavy machines and large scaled receiver system of communication equipment are manufactured, it always needs to produce large-sized steel castings, aluminum castings and etc. Some defects of hot cracking by thermal stress often appear during solidification process as these castings are produced, which results in failure of castings. Therefore predicting the effects of technological parameters for production of castings on the thermal stress during solidification process becomes an important means. In this paper, the mathematical models have been established and numerical calculation of temperature fields by using finite difference method (FDM) and then thermal stress fields by using finite element method (FEM) during solidification process of castings have been carried out. The technological parameters of production have been optimized by the results of calculation and the defects of hot cracking have been eliminated. Modeling and simulation of 3D thermal stress during solidification processes of large-sized castings provided a scientific basis, which promoted further development of advanced manufacturing technique.
文摘Recently, research strives to apply Ultra High Performance Concrete (UHPC) to large-sized structures owing to its remarkable mechanical performance and durability compared to normal concrete. The Korea Institute of Construction Technology proposed SuperBridge800, an edge girder type UHPC cable stayed bridge with central span of 800 m, through its detailed design. The bridge is designed to be erected through the connection of precast UHPC segments. The precast UHPC segment is monolithically composed of one ribbed deck slab and edge girders at each side. The connection between the precast segments is achieved by steel bars at the edge girders and by UHPC cast-in-place wet joint at the slab. Despite of the outstanding mechanical performance of UHPC, the fabrication of large-sized members is a difficult task since UHPC hardens faster than normal concrete and requires a special curing process. Therefore, the constructability of large-sized UHPC segment should be secured to achieve SuperBridge800. Besides, the performance of the connection between segments should also be guaranteed, especially in terms of the fatigue performance of the UHPC cast-in-place joint, which constitutes a weak point. To that goal, two half-scaled UHPC segments are manufactured and the constructability is examined by fabricating a large-sized UHPC member connected with respect to the design conditions. This study conducts rolling fatigue test on the so-fabricated large-sized UHPC member. Rolling fatigue test is carried out up to 2 million cycles considering actual vehicle load at each center and quarter points of the member. The test results confirm that the service limit state is satisfied.
文摘Large-sized aluminum tube has big section effect, aspect ratio and thin thickness, so that the extrusion technology is complex and the large specific pressure is generated in extrusion cavity. The temperature variation and velocity effect is difficult to control. The extrusion forming of large-sized aluminum tube was researched and simulated. Three-dimensional thermo-mechanical coupled finite element model was constructed and appropriate boundary conditions were given out. The results show that large-sized aluminum tube can be formed by isothermal extrusion through controlling the extrusion velocity and founding the relationship between extrusion velocity and extrusion temperature.
文摘Background:Despite advances in the diagnosis of patients with hepatocellular carcinoma(HCC),70%-80%of patients are diagnosed with advanced stage disease.Portal vein tumor thrombus(PVTT)is among the most ominous signs of advanced stage disease and has been associated with poor survival if untreated.Data sources:A systematic search of MEDLINE(PubMed),Embase,Cochrane Library and Database for Systematic Reviews(CDSR),Google Scholar,and National Institute for Health and Clinical Excellence(NICE)databases until December 2022 was conducted using free text and MeSH terms:hepatocellular carcinoma,portal vein tumor thrombus,portal vein thrombosis,vascular invasion,liver and/or hepatic resection,liver transplantation,and systematic review.Results:Centers of surgical excellence have reported promising results related to the individualized surgical management of portal thrombus versus arterial chemoembolization or systemic chemotherapy.Critical elements to the individualized surgical management of HCC and portal thrombus include precise classification of the portal vein tumor thrombus,accurate identification of the subgroups of patients who may benefit from resection,as well as meticulous surgical technique.This review addressed five specific areas:(a)formation of PVTT;(b)classifications of PVTT;(c)controversies related to clinical guidelines;(d)surgical treatments versus non-surgical approaches;and(e)characterization of surgical techniques correlated with classifications of PVTT.Conclusions:Current evidence from Chinese and Japanese high-volume centers demonstrated that patients with HCC and associated PVTT can be managed with surgical resection with acceptable results.
基金National Key R&D Program of China,No.2022YFF1203300.
文摘BACKGROUND Tumor budding(TB)has emerged as a promising independent prognostic biomarker in colorectal cancer(CRC).The prognostic role of TB has been extensively studied and currently affects clinical decision making in patients with stage I and II CRC.However,existing prognostic studies on TB in stage III CRC have been confined to small retrospective cohort studies.Consequently,this study investigated the correlation among TB categories,clinicopathological features,and prognosis in stage III-IV CRC to further enhance the precision and individualization of treatment through refined prognostic risk stratification.AIM To analyze the relationship between TB categories and clinicopathological characteristics and assess their prognostic value in stage III-IV CRC to further refine the prognostic risk stratification of stage III-IV CRC.METHODS The clinical data of 547 CRC patients were collected for this retrospective study.Infiltration at the front edge of the tumor buds was counted according to the 2016 International Tumor Budding Consensus Conference guidelines.RESULTS Multivariate Cox proportional hazards regression analysis demonstrated that chemotherapy(P=0.004),clinical stage IV(P<0.001),≥4 regional lymph node metastases(P=0.004),left-sided colonic cancer(P=0.040),and Bd 2-3(P=0.002)were independent prognostic factors in patients with stage III-IV CRC.Moreover,the density of tumor infiltrating lymphocytes was higher in Bd 1 than in Bd 2-3,both in the tumor stroma and its invasive margin.CONCLUSION TB has an independent predictive prognostic value in patients with stage III-IV CRC.It is recommended to complete the TB report of stage III-IV CRC cases in the standardized pathological report to further refine risk stratification.
基金Supported by National Natural Science Foundation of China,No.82074450Education Department of Hunan Province,No.21A0243,No.21B0374,No.22B0397,and No.22B0392+2 种基金Research Project of"Academician Liu Liang Workstation"of Hunan University of Traditional Chinese Medicine,No.21YS003Hunan Administration of Traditional Chinese Medicine,No.B2023001 and No.B2023009Hunan Provincial Natural Science Foundation of China,No.2023JJ40481。
文摘BACKGROUND Calculus bovis(CB),used in traditional Chinese medicine,exhibits anti-tumor effects in various cancer models.It also constitutes an integral component of a compound formulation known as Pien Tze Huang,which is indicated for the treatment of liver cancer.However,its impact on the liver cancer tumor microenvironment,particularly on tumor-associated macrophages(TAMs),is not well understood.AIM To elucidate the anti-liver cancer effect of CB by inhibiting M2-TAM polarization via Wnt/β-catenin pathway modulation.METHODS This study identified the active components of CB using UPLC-Q-TOF-MS,evaluated its anti-neoplastic effects in a nude mouse model,and elucidated the underlying mechanisms via network pharmacology,transcriptomics,and molecular docking.In vitro assays were used to investigate the effects of CB-containing serum on HepG2 cells and M2-TAMs,and Wnt pathway modulation was validated by real-time reverse transcriptase-polymerase chain reaction and Western blot analysis.RESULTS This study identified 22 active components in CB,11 of which were detected in the bloodstream.Preclinical investigations have demonstrated the ability of CB to effectively inhibit liver tumor growth.An integrated approach employing network pharmacology,transcriptomics,and molecular docking implicated the Wnt signaling pathway as a target of the antineoplastic activity of CB by suppressing M2-TAM polarization.In vitro and in vivo experiments further confirmed that CB significantly hinders M2-TAM polarization and suppresses Wnt/β-catenin pathway activation.The inhibitory effect of CB on M2-TAMs was reversed when treated with the Wnt agonist SKL2001,confirming its pathway specificity.CONCLUSION This study demonstrated that CB mediates inhibition of M2-TAM polarization through the Wnt/β-catenin pathway,contributing to the suppression of liver cancer growth.
文摘BACKGROUND Pediatric pancreatic tumors are rare and account for<0.1%of all childhood cancers.The primary treatment for pancreatic tumors is surgical resection.However,because of the lack of knowledge regarding pediatric pancreatic tumors,no comprehensive treatment plans for pediatric pancreatic tumors have been developed.AIM To compared the clinical features,treatment methods,and prognosis of pediatric pancreatic tumors in Japan with those in other countries.METHODS Questionnaires were sent to 213 pediatric surgical units in Japan.Pancreatic tumors that were not surgically treated were excluded from the survey.The primary survey investigated the number of patients aged 0-18 years who underwent pancreatic tumor surgery and the type of tumors managed during the 22-year study period(from January 1,2000 to December 31,2021)by post card.The secondary survey assessed the clinical images,treatment methods,and tumor outcomes via email.RESULTS The primary survey enrolled 228 patients.In the secondary survey,213 patients were eventually enrolled.The most common type of pancreatic tumor was solid pseudopapillary neoplasm(SPN)[n=164(77.0%)],followed by pancreatoblastoma[n=16(7.5%)],pancreatic endocrine tumor[n=14(6.6%)],non-epithelial tumor[n=9(4.2%)],pancreatic tumor[n=7(3.3%)],and metastatic pancreatic tumor[n=3(1.4%)].Overall,123(57.7%)patients underwent distal pancreatectomy,of whom 49 underwent laparoscopic surgery.Forty-four(20.7%)patients underwent enucleation,of whom eight underwent laparoscopic surgery.Thirty-two(15.0%)patients underwent pancreaticoduodenectomy,of whom one underwent laparoscopic surgery.All patients with SPN,including those with distant metastases and recurrent disease,survived.CONCLUSION SPN was more common in Japan than in other countries.Regardless of the histological type,resection is the most effective treatment for pediatric pancreatic tumors.
文摘Simulation technique is an efficient approach to realize the planning and scheduling of manufacturing process of products. An appropriate and efficient manufacturing process model is the basis and key of manufacturing process simulation. By analyzing the features of large-sized and complex products, a method of manufacturing process modeling based on activity network is presented and a mapping algorithm of translating BOM/BOP into the manufacturing process model is designed in detail.
文摘BACKGROUND Most patients with advanced pancreatic neuroendocrine tumors(pNETs)die due to tumor progression.Therefore,identifying new therapies with low toxicity and good tolerability to use concomitantly with the established pNET treatment is relevant.In this perspective,metformin is emerging as a molecule of interest.Retrospective studies have described metformin,a widely used agent for the treatment of patients with type 2 diabetes mellitus(T2DM),to be effective in modulating different tumor-related events,including cancer incidence,recurrence and survival by inhibiting mTOR phosphorylation.This systematic review evaluates the role of T2DM and metformin in the insurgence and post-treatment outcomes in patients with pNET.AIM To systematically analyze and summarize evidence related to the diagnostic and prognostic value of T2DM and metformin for predicting the insurgence and posttreatment outcomes of pNET.METHODS A systematic review of the published literature was undertaken,focusing on the role of T2DM and metformin in insurgence and prognosis of pNET,measured through outcomes of tumor-free survival(TFS),overall survival and progression free survival.RESULTS A total of 13 studies(5674 patients)were included in this review.Analysis of 809 pNET cases from five retrospective studies(low study heterogeneity with I^(2)=0%)confirms the correlation between T2DM and insurgence of pNET(OR=2.13,95%CI=1.56-4.55;P<0.001).The pooled data from 1174 pNET patients showed the correlation between T2DM and post-treatment TFS in pNET patients(hazard ratio=1.84,95%CI=0.78-2.90;P<0.001).The study heterogeneity was intermediate,with I^(2)=51%.A few studies limited the possibility of performing pooled analysis in the setting of metformin;therefore,results were heterogeneous,with no statistical relevance to the use of this drug in the diagnosis and prognosis of pNET.CONCLUSION T2DM represents a risk factor for the insurgence of pNET and is a significant predictor of poor post-treatment TFS of pNET patients.Unfortunately,a few studies with heterogeneous results limited the possibility of exploring the effect of metformin in the diagnosis and prognosis of pNET.
基金supported by the National Natural Science Foundation of China (No. 82203056)Natural Science Foundation of Liaoning Province (No. 2023-BS-167)+1 种基金Science and Technology Talent Innovation Support Plan of Dalian (No. 2022RQ091)“1+X” program for Clinical Competency Enhancement–Clinical Research Incubation Project of the Second Hospital of Dalian Medical University (No. 2022LCYJYB01)。
文摘Throughout tumorigenesis, the co-evolution of tumor cells and their surrounding microenvironment leads to the development of malignant phenotypes. Cellular communication within the tumor microenvironment(TME) plays a critical role in influencing various aspects of tumor progression, including invasion and metastasis. The release of exosomes, a type of extracellular vesicle, by most cell types in the body, is an essential mediator of intercellular communication. A growing body of research indicates that tumor-derived exosomes(TDEs) significantly expedite tumor progression through multiple mechanisms, inducing epithelial-mesenchymal transition and macrophage polarization, enhancing angiogenesis, and aiding in the immune evasion of tumor cells. Herein, we describe the formation and characteristics of the TME, and summarize the contents of TDEs and their diverse functions in modulating tumor development. Furthermore, we explore potential applications of TDEs in tumor diagnosis and treatment.
基金Supported by the National Institutes of Health grants,No.K99HL146954 and No.R00HL146954the UTHSC College of Pharmacy Research Seed Grant award,No.2023.
文摘Despite significant advances in our understanding of the molecular pathogenesis of liver cancer and the availability of novel pharmacotherapies,liver cancer remains the fourth leading cause of cancer-related mortality worldwide.Tumor relapse,resistance to current anti-cancer drugs,metastasis,and organ toxicity are the major challenges that prevent considerable improvements in patient survival and quality of life.Calculus bovis(CB),an ancient Chinese medicinal drug,has been used to treat various pathologies,including stroke,convulsion,epilepsy,pain,and cancer.In this editorial,we discuss the research findings recently published by Huang et al on the therapeutic effects of CB in inhibiting the development of liver cancer.Utilizing the comprehensive transcriptomic analyses,in vitro experiments,and in vivo studies,the authors demonstrated that CB treatment inhibits the tumor-promoting M2 phenotype of tumor-associated macrophages via downregulating Wnt pathway.While multiple studies have been performed to explore the molecular mechanisms regulated by CB,this study uniquely shows its role in modulating the M2 phenotype of macrophages present within the tumor microenvironment.This study opens new avenues of future investigations aimed at investigating this drug’s efficacy in various mouse models including the effects of combination therapy,and against drug-resistant tumors.
基金supported the National Natural Science Foundation of China,No.81974178(to CD).
文摘Subarachnoid hemorrhage is associated with high morbidity and mortality and lacks effective treatment.Pyroptosis is a crucial mechanism underlying early brain injury after subarachnoid hemorrhage.Previous studies have confirmed that tumor necrosis factor-stimulated gene-6(TSG-6)can exert a neuroprotective effect by suppressing oxidative stress and apoptosis.However,no study to date has explored whether TSG-6 can alleviate pyroptosis in early brain injury after subarachnoid hemorrhage.In this study,a C57BL/6J mouse model of subarachnoid hemorrhage was established using the endovascular perforation method.Our results indicated that TSG-6 expression was predominantly detected in astrocytes,along with NLRC4 and gasdermin-D(GSDMD).The expression of NLRC4,GSDMD and its N-terminal domain(GSDMD-N),and cleaved caspase-1 was significantly enhanced after subarachnoid hemorrhage and accompanied by brain edema and neurological impairment.To explore how TSG-6 affects pyroptosis during early brain injury after subarachnoid hemorrhage,recombinant human TSG-6 or a siRNA targeting TSG-6 was injected into the cerebral ventricles.Exogenous TSG-6 administration downregulated the expression of NLRC4 and pyroptosis-associated proteins and alleviated brain edema and neurological deficits.Moreover,TSG-6 knockdown further increased the expression of NLRC4,which was accompanied by more severe astrocyte pyroptosis.In summary,our study revealed that TSG-6 provides neuroprotection against early brain injury after subarachnoid hemorrhage by suppressing NLRC4 inflammasome activation-induced astrocyte pyroptosis.