Russia on November 10 cleared the last major obstacle in its 18-year effort to join the World Trade Organization in what the head of the institution called a milestone for global trade. "It’s a victory for Russi...Russia on November 10 cleared the last major obstacle in its 18-year effort to join the World Trade Organization in what the head of the institution called a milestone for global trade. "It’s a victory for Russia, a victory for W.T.O. members, and a victory展开更多
The comprehensive pilot of China Telecom transformation was unveiled in Pudong of Shanghai a few days ago, which indicates comprehensive pilot projects starting formally. Huang WenLin, Vice President of China Telecom,...The comprehensive pilot of China Telecom transformation was unveiled in Pudong of Shanghai a few days ago, which indicates comprehensive pilot projects starting formally. Huang WenLin, Vice President of China Telecom, attends the unveiling ceremony and proposes four requirements.展开更多
Clear aligner treatment is a novel technique in current orthodontic practice.Distinct from traditional fixed orthodontic appliances,clear aligners have different material features and biomechanical characteristics and...Clear aligner treatment is a novel technique in current orthodontic practice.Distinct from traditional fixed orthodontic appliances,clear aligners have different material features and biomechanical characteristics and treatment efficiencies,presenting new clinical challenges.Therefore,a comprehensive and systematic description of the key clinical aspects of clear aligner treatment is essential to enhance treatment efficacy and facilitate the advancement and wide adoption of this new technique.This expert consensus discusses case selection and grading of treatment difficulty,principle of clear aligner therapy,clinical procedures and potential complications,which are crucial to the clinical success of clear aligner treatment.展开更多
Have you ever heard of a "refuge for stars"?Located at an average elevation of over 4,500 meters,Ngari Prefecture boasts world-class night-sky conditions due to minimal atmospheric pollution,abundant clear d...Have you ever heard of a "refuge for stars"?Located at an average elevation of over 4,500 meters,Ngari Prefecture boasts world-class night-sky conditions due to minimal atmospheric pollution,abundant clear days,high transparency,low humidity.展开更多
Types of paper Research Article A complete report on original research.A clear structure is required,including introduction,material and methods,results and discussion,conclusions generally.
Purpose–As an important part of the management of railway passenger transport,the rationality and effectiveness of the clearing method of railway passenger transport are directly related to the operating efficiency a...Purpose–As an important part of the management of railway passenger transport,the rationality and effectiveness of the clearing method of railway passenger transport are directly related to the operating efficiency and service quality of railway passenger transport enterprises.This paper aims to comprehensively and deeply discuss the evolution and development process of China’s railway passenger transport clearing method,analyze its characteristics and influences in each stage,identify the main factors affecting its evolution and development and then put forward thoughts on improving the future development of the clearing method.Design/methodology/approach–Through a detailed review of the railway passenger transport clearing methods from the planned economy period to the reform and opening up period and into the new century,the basis,mode,subject and object of clearing in different development stages are systematically compared.Findings–It comprehensively reveals the evolution of the clearing method,sorted out the characteristics and changes of the clearing method at each stage and the adaptability to the development of railway passenger transport at that time.The characteristics of the development of clearing measures for railway passenger transport in different stages and their far-reaching influence on railway passenger transport business are deeply analyzed.Originality/value–This paper summarized the factors influencing the development of China’s railway passenger transportation clearing approach evolution,including the simplified rules of clearing,enhanced the market adaptability,establishing and perfecting the incentive mechanism,strengthening the construction of informatization,etc.This paper puts forward the ways to improve the railway passenger transportation clearing future development thinking.展开更多
In late May,the city of Dunhuang,a key historical hub of Eastern and Western cultures in Northwest China's Gansu Province,basked in clear and refreshing weather under a brilliant blue sky.The rugged Mingsha Mounta...In late May,the city of Dunhuang,a key historical hub of Eastern and Western cultures in Northwest China's Gansu Province,basked in clear and refreshing weather under a brilliant blue sky.The rugged Mingsha Mountain,renowned for the musical sounds produced by wind-blown sands when the wind blows,stood in silent majesty.To the close north of the mountain's massive golden dunes stood the city's international convention centre,where some 400 vips from 60 countries host cultural exchanges and mutual learning.展开更多
Background:This research aims to investigate potential gene targets and mechanisms through which the traditional Chinese medicine(TCM)Bupleuri Radix(Chaihu)may impact on clear cell renal cell carcinoma(ccRCC)treatment...Background:This research aims to investigate potential gene targets and mechanisms through which the traditional Chinese medicine(TCM)Bupleuri Radix(Chaihu)may impact on clear cell renal cell carcinoma(ccRCC)treatment.Methods:Public databases were employed to identify Cedrenol,an active component of Bupleuri Radix,and its associated gene targets.Among these,the gene RORC(also known as RORγ)was selected for detailed analysis due to its high expression correlation.Expression levels of RORC across various cancers were assessed using the TCGA pan-cancer dataset.Further analyses,including differential expression,prognostic relevance,immune infiltration,single-gene,and functional enrichment analyses,were conducted using the TCGA ccRCC dataset.Additionally,potential drug sensitivities and molecular docking interactions with RORC were explored using the GSCALite and CellMiner databases.The effects of RORC on ccRCC were also validated through cellular experiments.Results:RORC exhibited elevated expression in clear cell renal carcinoma tissue in contrast to normal tissues,and lower RORC expression was related to better prognosis.Immune cell infiltration analysis suggested that RORC may influence the penetration of cells that inhibit immune responses,such as regulatory T cells,thereby affecting ccRCC progression.Furthermore,molecular docking studies revealed that several drugs,including Axitinib,Docetaxel,Methotrexate,and Temsirolimus,have a high affinity for RORC and exhibit strong molecular binding.In cellular experiment experiments confirmed that RORC knockdown led to reduced proliferation,metastasis,and ccRCC cell invasion.Conclusion:The study implies that RORC may be a potential gene target for Bupleuri Radix in the management of ccRCC.展开更多
BACKGROUND Metastasis of renal cell carcinoma(RCC)to the skeletal muscle and small bowel is an exceedingly rare occurrence.Both of these sites are unusual sites for RCC to metastasize to and to occur simultaneously is...BACKGROUND Metastasis of renal cell carcinoma(RCC)to the skeletal muscle and small bowel is an exceedingly rare occurrence.Both of these sites are unusual sites for RCC to metastasize to and to occur simultaneously is even less common.CASE SUMMARY A 58-year-old male with known history of RCC presented with a recurrence that was diagnosed through imaging and biopsies.Mucosa abnormalities of small bowel noted during endoscopy were biopsied as well as lesion in the psoas muscle that was noted.CONCLUSION This case report emphasizes that RCC can not only recur but can do so even decades later and present as metastatic foci at atypical sites.展开更多
Dear Editor,The mammalian brain exhibits cross-scale complexity in neuronal morphology and connectivity,the study of which demands high-resolution morphological reconstruction of individual neurons across the entire b...Dear Editor,The mammalian brain exhibits cross-scale complexity in neuronal morphology and connectivity,the study of which demands high-resolution morphological reconstruction of individual neurons across the entire brain[1-4].Current commonly used approaches for such mesoscale brain mapping include two main types of three-dimensional fluorescence microscopy:the block-face methods,and the lightsheet-based methods[5,6].In general,the high imaging speed and light efficiency of light-sheet microscopy make it a suitable tool for high-throughput volumetric imaging,especially when combined with tissue-clearing techniques.However,large brain samples pose major challenges to this approach.展开更多
Introduction Human papillomavirus(HPV)vaccination is a cornerstone of cervical cancer prevention,particularly in low-and middle-income countries(LMICs),where the burden of disease remains high~1.The World Health Organ...Introduction Human papillomavirus(HPV)vaccination is a cornerstone of cervical cancer prevention,particularly in low-and middle-income countries(LMICs),where the burden of disease remains high~1.The World Health Organization(WHO)HPV Vaccine Introduction Clearing House reported that 147 countries(of 194 reporting)had fully introduced the HPV vaccine into their national schedules as of 20242.After COVID-19 pandemic disruptions,global coverage is again increasing.展开更多
Background:Clear cell renal carcinoma(ccRCC),the leading histological subtype of RCC,lacks any targeted therapy options.Although some studies have shown that early growth response factor 1(EGR1)has a significant role ...Background:Clear cell renal carcinoma(ccRCC),the leading histological subtype of RCC,lacks any targeted therapy options.Although some studies have shown that early growth response factor 1(EGR1)has a significant role in cancer development and progression,its role and underlying mechanisms in ccRCC remain poorly understood.Methods:The Cancer Genome Atlas(TCGA)database was utilized to examine the expression of EGR1 in ccRCC.The expression of EGR1 in 55 ccRCC tissues was evaluated using immunohistochemistry.The link between EGR1 expression and clinicopathological variables was examined through an analysis.Gain-of-function assays were employed to investigate EGR1’s biological functions in ccRCC cells,involving proliferation,colony formation,invasion assays,and tumorigenesis in nude mice.In order to assess the protein expression of mitogen-activated protein kinase 15(MAPK15),E-cadherin,matrix metalloproteinase-9/-2(MMP-9 and MMP-2),Western blot technique was applied.Results:The results revealed a decrease in EGR1 expression in ccRCC tissues.This decrease was strongly linked to TNM stage,lymphatic metastasis,tumor size,histological grade,and unfavorable prognosis in ccRCC patients.It has been demonstrated that overexpressing EGR1 inhibits the growth of xenograft tumors in vivo and inhibits cell colony formation,motility,and invasion in vitro.Furthermore,EGR1 can prevent the development and movement of ccRCC cells by controlling the expression of MMP-2,MMP-9,E-cadherin,and MAPK15.Conclusions:The EGR1/MAPK15 axis may represent a promising target for drug development,with EGR1 serving as a possible target for ccRCC therapy.展开更多
Background:Clear cell renal cell carcinoma(ccRCC)is an aggressive malignancy associated with limited treatment options and poor prognosis.Emerging studies suggest that the actin-regulating protein actin-related protei...Background:Clear cell renal cell carcinoma(ccRCC)is an aggressive malignancy associated with limited treatment options and poor prognosis.Emerging studies suggest that the actin-regulating protein actin-related protein 2/3 complex subunit 1B(ARPC1B),a key regulatory protein within the actin cytoskeleton,could play a pivotal role in ccRCC progression.The current study aimed to uncover the biological functions of ARPC1B and the molecular mechanisms driving its effects in ccRCC.Methods:ARPC1B expression and prognostic implications were analyzed using data sourced from the Gene Expression Profiling Interactive Analysis(GEPIA)platform,immunohistochemical(IHC)staining on 150 tumor samples along with 30 corresponding normal tissues,and Western blotting(WB)analyses across multiple ccRCC-derived cell lines.Functional assays assessing cell proliferation,colony formation capability,migration,invasion,and in vivo tumorigenicity were conducted following either ARPC1B suppression or upregulation.Additionally,WB analysis was utilized to evaluate proteins linked to epithelial-to-mesenchymal transition(EMT)and the Wnt/β-catenin pathway.Results:The findings revealed a substantial elevation of ARPC1B in ccRCC tissues and cell lines,significantly associated with advanced TNM stages,higher Fuhrman grades,and reduced overall survival(OS)(p<0.001).Multivariate statistical analysis identified ARPC1B as a standalone prognostic factor.Silencing ARPC1B notably impaired ccRCC cellular activities,and tumorigenesis in animalmodels,whereas augmented ARPC1B expression enhanced these malignant phenotypes.Mechanistically,downregulation of ARPC1B suppressed Wnt/β-catenin signaling and disrupted EMT,indicated by reducedβ-catenin,c-Myc,cyclin D1,and ZEB-1 levels,and concurrently increased E-cadherin expression.Additionally,reactivation of theWnt/β-catenin pathway partly reversed the inhibitory effects of ARPC1B depletion on tumor growth and invasiveness.Conclusions:ARPC1B emerges as an essential oncogenic factor in ccRCC by stimulating EMT and activating the Wnt/β-catenin pathway,ultimately enhancing tumor aggressiveness and metastatic potential.Thus,targeting ARPC1B represents a promising therapeutic strategy,warranting further exploration in ccRCC management.展开更多
BACKGROUND Clear cell sarcoma(CCS)is a rare soft-tissue sarcoma.The most common metastatic sites for CCS are the lungs,bones and brain.CCS is highly invasive and mainly metastasizes to the lung,followed by the bone an...BACKGROUND Clear cell sarcoma(CCS)is a rare soft-tissue sarcoma.The most common metastatic sites for CCS are the lungs,bones and brain.CCS is highly invasive and mainly metastasizes to the lung,followed by the bone and brain;however,pancreatic metastasis is relatively rare.CASE SUMMARY We report on a rare case of CCS with pancreatic metastasis in a 47-year-old man.The patient had a relevant medical history 3 years ago,with abdominal pain as the main clinical manifestation.No abnormalities were observed on physical examination and the tumor was found on abdominal computed tomography.Based on the medical history and postoperative pathology,the patient was diagnosed with CCS with pancreatic metastasis.The patient was successfully treated with surgical interventions,including distal pancreatectomy and sple-nectomy.CONCLUSION This report summarizes the available treatment modalities for CCS and the importance of regular postoperative follow-up for patients with CCS.展开更多
Mitochondrial dysfunction is a hallmark of Alzheimer’s disease.We previously showed that neural stem cell-derived extracellular vesicles improved mitochondrial function in the cortex of AP P/PS1 mice.Because Alzheime...Mitochondrial dysfunction is a hallmark of Alzheimer’s disease.We previously showed that neural stem cell-derived extracellular vesicles improved mitochondrial function in the cortex of AP P/PS1 mice.Because Alzheimer’s disease affects the entire brain,further research is needed to elucidate alterations in mitochondrial metabolism in the brain as a whole.Here,we investigated the expression of several important mitochondrial biogenesis-related cytokines in multiple brain regions after treatment with neural stem cell-derived exosomes and used a combination of whole brain clearing,immunostaining,and lightsheet imaging to clarify their spatial distribution.Additionally,to clarify whether the sirtuin 1(SIRT1)-related pathway plays a regulatory role in neural stem cell-de rived exosomes interfering with mitochondrial functional changes,we generated a novel nervous system-SIRT1 conditional knoc kout AP P/PS1mouse model.Our findings demonstrate that neural stem cell-de rived exosomes significantly increase SIRT1 levels,enhance the production of mitochondrial biogenesis-related fa ctors,and inhibit astrocyte activation,but do not suppress amyloid-βproduction.Thus,neural stem cell-derived exosomes may be a useful therapeutic strategy for Alzheimer’s disease that activates the SIRT1-PGC1αsignaling pathway and increases NRF1 and COXIV synthesis to improve mitochondrial biogenesis.In addition,we showed that the spatial distribution of mitochondrial biogenesis-related factors is disrupted in Alzheimer’s disease,and that neural stem cell-derived exosome treatment can reverse this effect,indicating that neural stem cell-derived exosomes promote mitochondrial biogenesis.展开更多
BACKGROUND Endobronchial metastases(EBMs)are tumours that metastasise from a malignant tumour outside the lungs to the central and subsegmental bronchi,and are visible under a bronchofibrescope.Most EBMs are formed by...BACKGROUND Endobronchial metastases(EBMs)are tumours that metastasise from a malignant tumour outside the lungs to the central and subsegmental bronchi,and are visible under a bronchofibrescope.Most EBMs are formed by direct invasion or metastasis of intrathoracic malignant tumours,such as lung cancer,oesophageal cancer or mediastinum tumours.Renal cell carcinoma(RCC),accounting for 2%to 3%of all tumours,is a common malignant tumour of the urinary system.Renal clear cell carcinoma(RCCC)constitutes the predominant pathological subtype of RCC,comprising approximately 70%to 80%of all RCC cases.RCCC can spread and metastasise through arterial,venous and lymphatic circulation to almost all organs of the body.Moreover,lung,bone,liver,brain and local recurrence are the most common metastatic neoplasms of RCCC.However,EBM from RCCC has a low complication rate and is often misdiagnosed as primary lung cancer.CASE SUMMARY A 71-year-old male patient who had undergone radical left nephrectomy 7 years prior due to RCCC was referred to our hospital due to a 1-mo history of productive cough.The results of an enhanced chest CT scan indicated the presence of a soft tissue nodule in the upper lobe of the left lung,and flexible bronchoscopy revealed a hypervascular lesion in the bronchus of the left lung's superior lobe.Therefore,the patient underwent thoracoscopic left superior lobe wedge resection,and pathology confirmed EBM from the RCCC.CONCLUSION EBM from RCCC has a low incidence and no characteristic clinical manifestations in the early stage.If a bronchial tumour is found in a patient with RCCC,the possibility of bronchial metastatic cancer should be considered.展开更多
文摘Russia on November 10 cleared the last major obstacle in its 18-year effort to join the World Trade Organization in what the head of the institution called a milestone for global trade. "It’s a victory for Russia, a victory for W.T.O. members, and a victory
文摘The comprehensive pilot of China Telecom transformation was unveiled in Pudong of Shanghai a few days ago, which indicates comprehensive pilot projects starting formally. Huang WenLin, Vice President of China Telecom, attends the unveiling ceremony and proposes four requirements.
文摘Clear aligner treatment is a novel technique in current orthodontic practice.Distinct from traditional fixed orthodontic appliances,clear aligners have different material features and biomechanical characteristics and treatment efficiencies,presenting new clinical challenges.Therefore,a comprehensive and systematic description of the key clinical aspects of clear aligner treatment is essential to enhance treatment efficacy and facilitate the advancement and wide adoption of this new technique.This expert consensus discusses case selection and grading of treatment difficulty,principle of clear aligner therapy,clinical procedures and potential complications,which are crucial to the clinical success of clear aligner treatment.
文摘Have you ever heard of a "refuge for stars"?Located at an average elevation of over 4,500 meters,Ngari Prefecture boasts world-class night-sky conditions due to minimal atmospheric pollution,abundant clear days,high transparency,low humidity.
文摘Types of paper Research Article A complete report on original research.A clear structure is required,including introduction,material and methods,results and discussion,conclusions generally.
基金supported by the Research and Development Plan Project of China State Railway Group Co.,Ltd.(Project No.P2023X029).
文摘Purpose–As an important part of the management of railway passenger transport,the rationality and effectiveness of the clearing method of railway passenger transport are directly related to the operating efficiency and service quality of railway passenger transport enterprises.This paper aims to comprehensively and deeply discuss the evolution and development process of China’s railway passenger transport clearing method,analyze its characteristics and influences in each stage,identify the main factors affecting its evolution and development and then put forward thoughts on improving the future development of the clearing method.Design/methodology/approach–Through a detailed review of the railway passenger transport clearing methods from the planned economy period to the reform and opening up period and into the new century,the basis,mode,subject and object of clearing in different development stages are systematically compared.Findings–It comprehensively reveals the evolution of the clearing method,sorted out the characteristics and changes of the clearing method at each stage and the adaptability to the development of railway passenger transport at that time.The characteristics of the development of clearing measures for railway passenger transport in different stages and their far-reaching influence on railway passenger transport business are deeply analyzed.Originality/value–This paper summarized the factors influencing the development of China’s railway passenger transportation clearing approach evolution,including the simplified rules of clearing,enhanced the market adaptability,establishing and perfecting the incentive mechanism,strengthening the construction of informatization,etc.This paper puts forward the ways to improve the railway passenger transportation clearing future development thinking.
文摘In late May,the city of Dunhuang,a key historical hub of Eastern and Western cultures in Northwest China's Gansu Province,basked in clear and refreshing weather under a brilliant blue sky.The rugged Mingsha Mountain,renowned for the musical sounds produced by wind-blown sands when the wind blows,stood in silent majesty.To the close north of the mountain's massive golden dunes stood the city's international convention centre,where some 400 vips from 60 countries host cultural exchanges and mutual learning.
基金supported by Hubei Provincial Department of Science and Technology,Innovation and Development Joint Fund(No.2022CFD145)Young Talents Project of Hubei Provincial Administration of Traditional Chinese Medicine(No.ZY2023Q002).
文摘Background:This research aims to investigate potential gene targets and mechanisms through which the traditional Chinese medicine(TCM)Bupleuri Radix(Chaihu)may impact on clear cell renal cell carcinoma(ccRCC)treatment.Methods:Public databases were employed to identify Cedrenol,an active component of Bupleuri Radix,and its associated gene targets.Among these,the gene RORC(also known as RORγ)was selected for detailed analysis due to its high expression correlation.Expression levels of RORC across various cancers were assessed using the TCGA pan-cancer dataset.Further analyses,including differential expression,prognostic relevance,immune infiltration,single-gene,and functional enrichment analyses,were conducted using the TCGA ccRCC dataset.Additionally,potential drug sensitivities and molecular docking interactions with RORC were explored using the GSCALite and CellMiner databases.The effects of RORC on ccRCC were also validated through cellular experiments.Results:RORC exhibited elevated expression in clear cell renal carcinoma tissue in contrast to normal tissues,and lower RORC expression was related to better prognosis.Immune cell infiltration analysis suggested that RORC may influence the penetration of cells that inhibit immune responses,such as regulatory T cells,thereby affecting ccRCC progression.Furthermore,molecular docking studies revealed that several drugs,including Axitinib,Docetaxel,Methotrexate,and Temsirolimus,have a high affinity for RORC and exhibit strong molecular binding.In cellular experiment experiments confirmed that RORC knockdown led to reduced proliferation,metastasis,and ccRCC cell invasion.Conclusion:The study implies that RORC may be a potential gene target for Bupleuri Radix in the management of ccRCC.
文摘BACKGROUND Metastasis of renal cell carcinoma(RCC)to the skeletal muscle and small bowel is an exceedingly rare occurrence.Both of these sites are unusual sites for RCC to metastasize to and to occur simultaneously is even less common.CASE SUMMARY A 58-year-old male with known history of RCC presented with a recurrence that was diagnosed through imaging and biopsies.Mucosa abnormalities of small bowel noted during endoscopy were biopsied as well as lesion in the psoas muscle that was noted.CONCLUSION This case report emphasizes that RCC can not only recur but can do so even decades later and present as metastatic foci at atypical sites.
基金supported by the STI 2030-Major Project(2021ZD0204400,2022ZD0205203,2021ZD0200104,2022ZD0211900)the Shenzhen Science and Technology Program(RCYX20210706092100003,RCBS20221008093311027)+3 种基金the Shenzhen Medical Research Funds(A2303005)the Youth Innovation Promotion Association CAS(2022367)the National Natural Science Foundation of China(32100896)NSFC-Guangdong Joint Fund(U20A6005).
文摘Dear Editor,The mammalian brain exhibits cross-scale complexity in neuronal morphology and connectivity,the study of which demands high-resolution morphological reconstruction of individual neurons across the entire brain[1-4].Current commonly used approaches for such mesoscale brain mapping include two main types of three-dimensional fluorescence microscopy:the block-face methods,and the lightsheet-based methods[5,6].In general,the high imaging speed and light efficiency of light-sheet microscopy make it a suitable tool for high-throughput volumetric imaging,especially when combined with tissue-clearing techniques.However,large brain samples pose major challenges to this approach.
文摘Introduction Human papillomavirus(HPV)vaccination is a cornerstone of cervical cancer prevention,particularly in low-and middle-income countries(LMICs),where the burden of disease remains high~1.The World Health Organization(WHO)HPV Vaccine Introduction Clearing House reported that 147 countries(of 194 reporting)had fully introduced the HPV vaccine into their national schedules as of 20242.After COVID-19 pandemic disruptions,global coverage is again increasing.
基金supported by grants from the Shenzhen Basic Research Project(JCYJ20210324125803008)the Shenzhen Longhua District Science and Innovation Bureau Fund for Medical Institutions(2022143).
文摘Background:Clear cell renal carcinoma(ccRCC),the leading histological subtype of RCC,lacks any targeted therapy options.Although some studies have shown that early growth response factor 1(EGR1)has a significant role in cancer development and progression,its role and underlying mechanisms in ccRCC remain poorly understood.Methods:The Cancer Genome Atlas(TCGA)database was utilized to examine the expression of EGR1 in ccRCC.The expression of EGR1 in 55 ccRCC tissues was evaluated using immunohistochemistry.The link between EGR1 expression and clinicopathological variables was examined through an analysis.Gain-of-function assays were employed to investigate EGR1’s biological functions in ccRCC cells,involving proliferation,colony formation,invasion assays,and tumorigenesis in nude mice.In order to assess the protein expression of mitogen-activated protein kinase 15(MAPK15),E-cadherin,matrix metalloproteinase-9/-2(MMP-9 and MMP-2),Western blot technique was applied.Results:The results revealed a decrease in EGR1 expression in ccRCC tissues.This decrease was strongly linked to TNM stage,lymphatic metastasis,tumor size,histological grade,and unfavorable prognosis in ccRCC patients.It has been demonstrated that overexpressing EGR1 inhibits the growth of xenograft tumors in vivo and inhibits cell colony formation,motility,and invasion in vitro.Furthermore,EGR1 can prevent the development and movement of ccRCC cells by controlling the expression of MMP-2,MMP-9,E-cadherin,and MAPK15.Conclusions:The EGR1/MAPK15 axis may represent a promising target for drug development,with EGR1 serving as a possible target for ccRCC therapy.
文摘Background:Clear cell renal cell carcinoma(ccRCC)is an aggressive malignancy associated with limited treatment options and poor prognosis.Emerging studies suggest that the actin-regulating protein actin-related protein 2/3 complex subunit 1B(ARPC1B),a key regulatory protein within the actin cytoskeleton,could play a pivotal role in ccRCC progression.The current study aimed to uncover the biological functions of ARPC1B and the molecular mechanisms driving its effects in ccRCC.Methods:ARPC1B expression and prognostic implications were analyzed using data sourced from the Gene Expression Profiling Interactive Analysis(GEPIA)platform,immunohistochemical(IHC)staining on 150 tumor samples along with 30 corresponding normal tissues,and Western blotting(WB)analyses across multiple ccRCC-derived cell lines.Functional assays assessing cell proliferation,colony formation capability,migration,invasion,and in vivo tumorigenicity were conducted following either ARPC1B suppression or upregulation.Additionally,WB analysis was utilized to evaluate proteins linked to epithelial-to-mesenchymal transition(EMT)and the Wnt/β-catenin pathway.Results:The findings revealed a substantial elevation of ARPC1B in ccRCC tissues and cell lines,significantly associated with advanced TNM stages,higher Fuhrman grades,and reduced overall survival(OS)(p<0.001).Multivariate statistical analysis identified ARPC1B as a standalone prognostic factor.Silencing ARPC1B notably impaired ccRCC cellular activities,and tumorigenesis in animalmodels,whereas augmented ARPC1B expression enhanced these malignant phenotypes.Mechanistically,downregulation of ARPC1B suppressed Wnt/β-catenin signaling and disrupted EMT,indicated by reducedβ-catenin,c-Myc,cyclin D1,and ZEB-1 levels,and concurrently increased E-cadherin expression.Additionally,reactivation of theWnt/β-catenin pathway partly reversed the inhibitory effects of ARPC1B depletion on tumor growth and invasiveness.Conclusions:ARPC1B emerges as an essential oncogenic factor in ccRCC by stimulating EMT and activating the Wnt/β-catenin pathway,ultimately enhancing tumor aggressiveness and metastatic potential.Thus,targeting ARPC1B represents a promising therapeutic strategy,warranting further exploration in ccRCC management.
文摘BACKGROUND Clear cell sarcoma(CCS)is a rare soft-tissue sarcoma.The most common metastatic sites for CCS are the lungs,bones and brain.CCS is highly invasive and mainly metastasizes to the lung,followed by the bone and brain;however,pancreatic metastasis is relatively rare.CASE SUMMARY We report on a rare case of CCS with pancreatic metastasis in a 47-year-old man.The patient had a relevant medical history 3 years ago,with abdominal pain as the main clinical manifestation.No abnormalities were observed on physical examination and the tumor was found on abdominal computed tomography.Based on the medical history and postoperative pathology,the patient was diagnosed with CCS with pancreatic metastasis.The patient was successfully treated with surgical interventions,including distal pancreatectomy and sple-nectomy.CONCLUSION This report summarizes the available treatment modalities for CCS and the importance of regular postoperative follow-up for patients with CCS.
基金supported by the National Natural Science Foundation of China,Nos.82171194 and 81974155(both to JL)the Shanghai Municipal Science and Technology Commission Medical Guide Project,No.16411969200(to WZ)Shanghai Municipal Science and Technology Commission Biomedical Science and Technology Project,No.22S31902600(to JL)。
文摘Mitochondrial dysfunction is a hallmark of Alzheimer’s disease.We previously showed that neural stem cell-derived extracellular vesicles improved mitochondrial function in the cortex of AP P/PS1 mice.Because Alzheimer’s disease affects the entire brain,further research is needed to elucidate alterations in mitochondrial metabolism in the brain as a whole.Here,we investigated the expression of several important mitochondrial biogenesis-related cytokines in multiple brain regions after treatment with neural stem cell-derived exosomes and used a combination of whole brain clearing,immunostaining,and lightsheet imaging to clarify their spatial distribution.Additionally,to clarify whether the sirtuin 1(SIRT1)-related pathway plays a regulatory role in neural stem cell-de rived exosomes interfering with mitochondrial functional changes,we generated a novel nervous system-SIRT1 conditional knoc kout AP P/PS1mouse model.Our findings demonstrate that neural stem cell-de rived exosomes significantly increase SIRT1 levels,enhance the production of mitochondrial biogenesis-related fa ctors,and inhibit astrocyte activation,but do not suppress amyloid-βproduction.Thus,neural stem cell-derived exosomes may be a useful therapeutic strategy for Alzheimer’s disease that activates the SIRT1-PGC1αsignaling pathway and increases NRF1 and COXIV synthesis to improve mitochondrial biogenesis.In addition,we showed that the spatial distribution of mitochondrial biogenesis-related factors is disrupted in Alzheimer’s disease,and that neural stem cell-derived exosome treatment can reverse this effect,indicating that neural stem cell-derived exosomes promote mitochondrial biogenesis.
文摘BACKGROUND Endobronchial metastases(EBMs)are tumours that metastasise from a malignant tumour outside the lungs to the central and subsegmental bronchi,and are visible under a bronchofibrescope.Most EBMs are formed by direct invasion or metastasis of intrathoracic malignant tumours,such as lung cancer,oesophageal cancer or mediastinum tumours.Renal cell carcinoma(RCC),accounting for 2%to 3%of all tumours,is a common malignant tumour of the urinary system.Renal clear cell carcinoma(RCCC)constitutes the predominant pathological subtype of RCC,comprising approximately 70%to 80%of all RCC cases.RCCC can spread and metastasise through arterial,venous and lymphatic circulation to almost all organs of the body.Moreover,lung,bone,liver,brain and local recurrence are the most common metastatic neoplasms of RCCC.However,EBM from RCCC has a low complication rate and is often misdiagnosed as primary lung cancer.CASE SUMMARY A 71-year-old male patient who had undergone radical left nephrectomy 7 years prior due to RCCC was referred to our hospital due to a 1-mo history of productive cough.The results of an enhanced chest CT scan indicated the presence of a soft tissue nodule in the upper lobe of the left lung,and flexible bronchoscopy revealed a hypervascular lesion in the bronchus of the left lung's superior lobe.Therefore,the patient underwent thoracoscopic left superior lobe wedge resection,and pathology confirmed EBM from the RCCC.CONCLUSION EBM from RCCC has a low incidence and no characteristic clinical manifestations in the early stage.If a bronchial tumour is found in a patient with RCCC,the possibility of bronchial metastatic cancer should be considered.
