BACKGROUND Cellular myofibroma is a rare subtype of myofibroma that was first described in 2017.Its diagnosis is often challenging because of its relative rarity,lack of known genetic abnormalities,and expression of m...BACKGROUND Cellular myofibroma is a rare subtype of myofibroma that was first described in 2017.Its diagnosis is often challenging because of its relative rarity,lack of known genetic abnormalities,and expression of muscle markers that can be confused with sarcomas that have myogenic differentiation.Currently,scholars have limited knowledge of this disease,and published cases are few.Further accumulation of diagnostic and treatment experiences is required.CASE SUMMARY A 16-year-old girl experienced left upper limb swelling for 3 years.She sought medical attention at a local hospital 10 months ago,where magnetic resonance imaging revealed a 5-cm soft tissue mass.Needle biopsy performed at a local hospital resulted in the diagnosis of a spindle cell soft tissue sarcoma.The patient was referred to our hospital for limb salvage surgery with endoprosthetic replacement.She was initially diagnosed with a synovial sarcoma.Consequently,clinical management with chemotherapy was continued for the malignant sarcoma.Our pathology department also performed fluorescence in situ hybridization for result validation,which returned negative for SS18 gene breaks,indicating that it was not a synovial sarcoma.Next-generation sequencing was used to identify the SRF-RELA rearrangement.The final pathological diagnosis was a cellular/myofibroblastic neoplasm with an SRF-RELA gene fusion.The patient had initially received two courses of chemotherapy;however,chemotherapy was discontinued after the final diagnosis.CONCLUSION This case was misdiagnosed because of its rare occurrence,benign biological behavior,and pathological similarity to soft tissue sarcoma.展开更多
Aflatoxin B_(1)(AFB_(1))is a naturally-occurring mycotoxin and recognized as the most toxic foodborne toxin,particularly causing damages to kidney.Glomerular podocytes are terminally differentiated epithelial cells.AF...Aflatoxin B_(1)(AFB_(1))is a naturally-occurring mycotoxin and recognized as the most toxic foodborne toxin,particularly causing damages to kidney.Glomerular podocytes are terminally differentiated epithelial cells.AFB_(1)induces podocyte inflammation,proteinuria and renal dysfunction.Studying the mechanism of AFB_(1)-induced podocyte inflammation and murine kidney dysfunction,we detected that AFB_(1)increased ubiquitindependent degradation of the transcription factor RelA through enhanced interaction of RelA with E3 ubiquitin ligase tripartite motif containing 7(TRIM7)in mouse podocyte clone-5(MPC-5)and mouse glomeruli.Reduction of RelA resulted in decreasing microRNA-9(miR-9)and activating the chemokine receptor 4(CXCR4),thioredoxin interacting protein(TXNIP),and NOD-like receptor pyrin domain-containing 3(NLRP3)signaling axis(CXCR4/TXNIP/NLRP3 pathway),leading to podocyte inflammation.We also determined that downregulation of miR-9 led to CXCR4 expression and the downstream TXNIP/NLRP3 pathway activation.Overexpression of miR-9 or deletion of CXCR4 suppressed AFB_(1)-induced CXCR4/TXNIP/NLRP3 pathway,resulting in alleviating podocyte inflammation and kidney dysfunction.Our findings indicated that ubiquitin-dependent proteolysis of RelA,downregulation of miR-9,and activation of CXCR4/TXNIP/NLRP3 pathway played an essential role in AFB_(1)-induced glomerular podocyte inflammation.Our study revealed a novel mechanism,via RelA,for the control of AFB_(1)’s nephrotoxicity,leading to an effective protection of food safety and public health.展开更多
BACKGROUND Ependymoma with lipomatous differentiation is a rare type of ependymoma.The ZFTA fusion-positive supratentorial ependymoma is a novel tumor type in the 2021 World Health Organization classification of centr...BACKGROUND Ependymoma with lipomatous differentiation is a rare type of ependymoma.The ZFTA fusion-positive supratentorial ependymoma is a novel tumor type in the 2021 World Health Organization classification of central nervous system tumors.ZFTA fusion-positive lipomatous ependymoma has not been reported to date.CASE SUMMARY We reported a case of a 15-year-old Chinese male who had a sudden convulsion lasting approximately six minutes.Magnetic resonance imaging showed a round cystic shadow of approximately 1.9 cm×1.5 cm×1.9 cm under the right parieto-occipital cortex.Microscopic examination showed characteristic perivascular pseudorosettes and adipose differentiation in the cytoplasm.Immunohisto-chemical staining showed that the tumor cells were negative for cytokeratin,NeuN,Syn and p53,but positive for GFAP,vimentin and S-100 protein.Signi-ficant punctate intracytoplasmic EMA immunoreactivity was observed.The level of Ki-67 was about 5%.Genetic analysis revealed ZFTA:RELA fusion.A cranio-tomy with total excision of the tumor was performed.The follow-up time was 36 months,no evidence of disease recurrence was found in magnetic resonance imaging.CONCLUSION Based on these findings,the patient was diagnosed as a ependymoma with ZFTA fusion and lipomatous differentiation.This case report provides information on the microscopic morphological features of ependymoma with ZFTA fusion and lipomatous differentiation,which can help pathologists to make a definitive diagnosis of this tumor.展开更多
Ependymoma is a rare and chemotherapy-resistant brain tumor, which has resulted in a delay in the development of drugs to treat it. A subclass of supratentorial ependymomas (ST-EPN), designated ST-EPN-zinc finger-tran...Ependymoma is a rare and chemotherapy-resistant brain tumor, which has resulted in a delay in the development of drugs to treat it. A subclass of supratentorial ependymomas (ST-EPN), designated ST-EPN-zinc finger-translocation-associated (ZFTA, ST-EPN-ZFTA), exhibits the expression of a fusion protein comprising ZFTA and v-rel reticuloendotheliosis viral oncogene homolog A (RELA), an effector transcription factor of the nuclear factor-kappa B (NF-κB) pathway (ZFTA-RELA). The expression of ZFTA-RELA results in the hyperactivation of the oncogenic NF-κB signaling pathway, which ultimately leads to the development of ST-EPN-ZFTA. To identify inhibitors of the NF-κB signaling pathway activated by the expression of ZFTA-RELA, we used a doxycycline-inducible ZFTA-RELA-expressing NF-κB reporter cell line and found that extracts of the fungus Neosartorya spinosa IFM 47025 exhibited NF-κB inhibitory activity. We identified eight compounds [aszonapyrone A (2), sartorypyrone A (3), epiheveadride (4), acetylaszonalenin (5), (R)-benzodiazepinedione (6), aszonalenin (7), sartorypyrone E (8) and (Z, Z)-N,N’-(1,2-bis[(4-methoxyphenyl)methylene]-1,2-ethanediyl)bis-formamide (9)] from N. spinosa IFM 47025 culture extract using a variety of chromatographic techniques. The structures of these compounds were identified through the analysis of various instrumental data (1D, 2D-NMR, MS, and optical rotation). The NF-κB responsive reporter assay indicated that compounds 2, 3, 5, 7, and 9 exhibited inhibitory activity. We further evaluated the inhibitory activity of these compounds against the expression of endogenous NF-κB responsive genes (CCND1, L1CAM, ICAM1, and TNF) and found that compound 2 showed significant inhibitory activity. Further studies are required to elucidate the mechanism of action of compound 2, which may serve as a lead compound for the development of a novel therapy for ST-EPN-ZFTA.展开更多
Nowadays, picture fuzzy set theory is a flourishing field in mathematics with uncertainty by incorporating the concept of positive, negative and neutral membership degrees of an object. A traditional crisp relation re...Nowadays, picture fuzzy set theory is a flourishing field in mathematics with uncertainty by incorporating the concept of positive, negative and neutral membership degrees of an object. A traditional crisp relation represents the satisfaction or the dissatisfaction of relationship, connection or correspondence between the objects of two or more sets. However, there are some problems that can’t be solved through classical relationships, such as the relationship between two objects being vague. In those situations, picture fuzzy relation over picture fuzzy sets is an important and powerful concept which is suitable for describing correspondences between two vague objects. It represents the strength of association of the elements of picture fuzzy sets. It plays an important role in picture fuzzy modeling, inference and control system and also has important applications in relational databases, approximate reasoning, preference modeling, medical diagnosis, etc. In this article, we define picture fuzzy relations over picture fuzzy sets, including some other fundamental definitions with illustrations. The max-min and min-max compositions of picture fuzzy relations are defined in the light of picture fuzzy sets and discussed some properties related to them. The reflexivity, symmetry and transitivity of a picture fuzzy relation are described over a picture fuzzy set. Finally, various properties are explored related to the picture fuzzy relations over a picture fuzzy set.展开更多
文摘BACKGROUND Cellular myofibroma is a rare subtype of myofibroma that was first described in 2017.Its diagnosis is often challenging because of its relative rarity,lack of known genetic abnormalities,and expression of muscle markers that can be confused with sarcomas that have myogenic differentiation.Currently,scholars have limited knowledge of this disease,and published cases are few.Further accumulation of diagnostic and treatment experiences is required.CASE SUMMARY A 16-year-old girl experienced left upper limb swelling for 3 years.She sought medical attention at a local hospital 10 months ago,where magnetic resonance imaging revealed a 5-cm soft tissue mass.Needle biopsy performed at a local hospital resulted in the diagnosis of a spindle cell soft tissue sarcoma.The patient was referred to our hospital for limb salvage surgery with endoprosthetic replacement.She was initially diagnosed with a synovial sarcoma.Consequently,clinical management with chemotherapy was continued for the malignant sarcoma.Our pathology department also performed fluorescence in situ hybridization for result validation,which returned negative for SS18 gene breaks,indicating that it was not a synovial sarcoma.Next-generation sequencing was used to identify the SRF-RELA rearrangement.The final pathological diagnosis was a cellular/myofibroblastic neoplasm with an SRF-RELA gene fusion.The patient had initially received two courses of chemotherapy;however,chemotherapy was discontinued after the final diagnosis.CONCLUSION This case was misdiagnosed because of its rare occurrence,benign biological behavior,and pathological similarity to soft tissue sarcoma.
基金funded by Suzhou Science and Technology Council(SNG201907)Universities Natural Science Foundation of Jiangsu Province(20KJB330002)+6 种基金General Program of China Postdoctoral Science Foundation(2022M711369)the Startup Funding of Soochow University,Jiangsu Province-Suzhou Science and Technology Planning Project(SL T201917)National Natural Science Foundation of China(32172922,31972741)Natural Science Foundation of Jiangsu Province of China(BK20211216,BK20221091)the Startup Funding of Hefei University of Technology(1302003712022058)China-CEEC Joint University Education Project(202010)the Excellence Project PrF UHK(2217/2022-2023)。
文摘Aflatoxin B_(1)(AFB_(1))is a naturally-occurring mycotoxin and recognized as the most toxic foodborne toxin,particularly causing damages to kidney.Glomerular podocytes are terminally differentiated epithelial cells.AFB_(1)induces podocyte inflammation,proteinuria and renal dysfunction.Studying the mechanism of AFB_(1)-induced podocyte inflammation and murine kidney dysfunction,we detected that AFB_(1)increased ubiquitindependent degradation of the transcription factor RelA through enhanced interaction of RelA with E3 ubiquitin ligase tripartite motif containing 7(TRIM7)in mouse podocyte clone-5(MPC-5)and mouse glomeruli.Reduction of RelA resulted in decreasing microRNA-9(miR-9)and activating the chemokine receptor 4(CXCR4),thioredoxin interacting protein(TXNIP),and NOD-like receptor pyrin domain-containing 3(NLRP3)signaling axis(CXCR4/TXNIP/NLRP3 pathway),leading to podocyte inflammation.We also determined that downregulation of miR-9 led to CXCR4 expression and the downstream TXNIP/NLRP3 pathway activation.Overexpression of miR-9 or deletion of CXCR4 suppressed AFB_(1)-induced CXCR4/TXNIP/NLRP3 pathway,resulting in alleviating podocyte inflammation and kidney dysfunction.Our findings indicated that ubiquitin-dependent proteolysis of RelA,downregulation of miR-9,and activation of CXCR4/TXNIP/NLRP3 pathway played an essential role in AFB_(1)-induced glomerular podocyte inflammation.Our study revealed a novel mechanism,via RelA,for the control of AFB_(1)’s nephrotoxicity,leading to an effective protection of food safety and public health.
文摘BACKGROUND Ependymoma with lipomatous differentiation is a rare type of ependymoma.The ZFTA fusion-positive supratentorial ependymoma is a novel tumor type in the 2021 World Health Organization classification of central nervous system tumors.ZFTA fusion-positive lipomatous ependymoma has not been reported to date.CASE SUMMARY We reported a case of a 15-year-old Chinese male who had a sudden convulsion lasting approximately six minutes.Magnetic resonance imaging showed a round cystic shadow of approximately 1.9 cm×1.5 cm×1.9 cm under the right parieto-occipital cortex.Microscopic examination showed characteristic perivascular pseudorosettes and adipose differentiation in the cytoplasm.Immunohisto-chemical staining showed that the tumor cells were negative for cytokeratin,NeuN,Syn and p53,but positive for GFAP,vimentin and S-100 protein.Signi-ficant punctate intracytoplasmic EMA immunoreactivity was observed.The level of Ki-67 was about 5%.Genetic analysis revealed ZFTA:RELA fusion.A cranio-tomy with total excision of the tumor was performed.The follow-up time was 36 months,no evidence of disease recurrence was found in magnetic resonance imaging.CONCLUSION Based on these findings,the patient was diagnosed as a ependymoma with ZFTA fusion and lipomatous differentiation.This case report provides information on the microscopic morphological features of ependymoma with ZFTA fusion and lipomatous differentiation,which can help pathologists to make a definitive diagnosis of this tumor.
文摘Ependymoma is a rare and chemotherapy-resistant brain tumor, which has resulted in a delay in the development of drugs to treat it. A subclass of supratentorial ependymomas (ST-EPN), designated ST-EPN-zinc finger-translocation-associated (ZFTA, ST-EPN-ZFTA), exhibits the expression of a fusion protein comprising ZFTA and v-rel reticuloendotheliosis viral oncogene homolog A (RELA), an effector transcription factor of the nuclear factor-kappa B (NF-κB) pathway (ZFTA-RELA). The expression of ZFTA-RELA results in the hyperactivation of the oncogenic NF-κB signaling pathway, which ultimately leads to the development of ST-EPN-ZFTA. To identify inhibitors of the NF-κB signaling pathway activated by the expression of ZFTA-RELA, we used a doxycycline-inducible ZFTA-RELA-expressing NF-κB reporter cell line and found that extracts of the fungus Neosartorya spinosa IFM 47025 exhibited NF-κB inhibitory activity. We identified eight compounds [aszonapyrone A (2), sartorypyrone A (3), epiheveadride (4), acetylaszonalenin (5), (R)-benzodiazepinedione (6), aszonalenin (7), sartorypyrone E (8) and (Z, Z)-N,N’-(1,2-bis[(4-methoxyphenyl)methylene]-1,2-ethanediyl)bis-formamide (9)] from N. spinosa IFM 47025 culture extract using a variety of chromatographic techniques. The structures of these compounds were identified through the analysis of various instrumental data (1D, 2D-NMR, MS, and optical rotation). The NF-κB responsive reporter assay indicated that compounds 2, 3, 5, 7, and 9 exhibited inhibitory activity. We further evaluated the inhibitory activity of these compounds against the expression of endogenous NF-κB responsive genes (CCND1, L1CAM, ICAM1, and TNF) and found that compound 2 showed significant inhibitory activity. Further studies are required to elucidate the mechanism of action of compound 2, which may serve as a lead compound for the development of a novel therapy for ST-EPN-ZFTA.
文摘Nowadays, picture fuzzy set theory is a flourishing field in mathematics with uncertainty by incorporating the concept of positive, negative and neutral membership degrees of an object. A traditional crisp relation represents the satisfaction or the dissatisfaction of relationship, connection or correspondence between the objects of two or more sets. However, there are some problems that can’t be solved through classical relationships, such as the relationship between two objects being vague. In those situations, picture fuzzy relation over picture fuzzy sets is an important and powerful concept which is suitable for describing correspondences between two vague objects. It represents the strength of association of the elements of picture fuzzy sets. It plays an important role in picture fuzzy modeling, inference and control system and also has important applications in relational databases, approximate reasoning, preference modeling, medical diagnosis, etc. In this article, we define picture fuzzy relations over picture fuzzy sets, including some other fundamental definitions with illustrations. The max-min and min-max compositions of picture fuzzy relations are defined in the light of picture fuzzy sets and discussed some properties related to them. The reflexivity, symmetry and transitivity of a picture fuzzy relation are described over a picture fuzzy set. Finally, various properties are explored related to the picture fuzzy relations over a picture fuzzy set.
