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Abstract Mining is vital for human sustenance and a crucial sector in the state economy. However, its impacts on the environment and biodiversity cannot be underestimated. Which are potent to the attract government's attention. Environment and wildlife are subject to the harmful impacts of mining and its related activities. In this study, districts, namely Mardan and Mohmand have been targeted with respect to mining impacts. The assessment was carried out on wildlife adversely affected by the mining sector. The fauna has been keenly observed to bring the calculated risks and threat perception of the regional wildlife. Total 9 species of mammals, 21 species of birds, were recorded in District Mardan. While in District Mohmand 2 species of mammals, 9 species of birds, and 4 species of reptiles were studied. The Study explored that mining primarily responsible for land degradation. Which lead to food and agriculture losses. Several other factors like blasting, pollution, hunting, deforestation, habitat loss was also observed. Deforestation surfaced one of the major causes for extinction of fauna in the said region. preemptive measures are needed to seize the man-made catastrophe.
Resumo A mineração é vital para o sustento humano e um setor crucial na economia do Estado. No entanto, seus impactos sobre o meio ambiente e a biodiversidade não podem ser subestimados, visto serem potentes para atrair a atenção do governo. O meio ambiente e a vida selvagem estão sujeitos aos impactos prejudiciais da mineração e de suas atividades relacionadas. Neste estudo, os distritos, nomeadamente Mardan e Mohmand, foram selecionados no que diz respeito aos impactos da mineração. A avaliação foi realizada em animais selvagens afetados negativamente pelo setor de mineração. A fauna tem sido observada atentamente para trazer os riscos calculados e a percepção de ameaça à vida selvagem regional. Um total de nove espécies de mamíferos, 21 espécies de pássaros, foi registrado no Distrito Mardan. Enquanto no Distrito Mohmand, duas espécies de mamíferos, nove espécies de pássaros e quatro espécies de répteis foram estudadas. O estudo explorou essa mineração que é principalmente responsável pela degradação do solo, acarretando perdas de alimentos e na agricultura. Vários outros fatores como explosões, poluição, caça, desmatamento, perda de habitat também foram observados. O desmatamento veio à tona como uma das principais causas de extinção da fauna da região, e tem-se que medidas preventivas são necessárias para dimensionar a catástrofe provocada pelo homem.
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Humanos , Animales , Biodiversidad , Animales Salvajes , Minería , PakistánRESUMEN
In the past few decades, microbubbles were widely used as ultrasound contrast agents in the field of tumor imaging. With the development of research, ultrasound targeted microbubble destruction technology combined with drug-loaded microbubbles can achieve precise drug release and play a therapeutic role. As a micron-scale carrier, microbubbles are difficult to penetrate the endothelial cell space of tumors, and nano-scale drug delivery system—nanobubbles came into being. The structure of the two is similar, but the difference in size highlights the unique advantages of nanobubbles in drug delivery. Based on the classification principle of shell materials, this review summarized micro/nanobubbles used for ultrasound diagnosis or treatment and discussed the possible development directions, providing references for the subsequent development.
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Abstract Mining is vital for human sustenance and a crucial sector in the state economy. However, its impacts on the environment and biodiversity cannot be underestimated. Which are potent to the attract governments attention. Environment and wildlife are subject to the harmful impacts of mining and its related activities. In this study, districts, namely Mardan and Mohmand have been targeted with respect to mining impacts. The assessment was carried out on wildlife adversely affected by the mining sector. The fauna has been keenly observed to bring the calculated risks and threat perception of the regional wildlife. Total 9 species of mammals, 21 species of birds, were recorded in District Mardan. While in District Mohmand 2 species of mammals, 9 species of birds, and 4 species of reptiles were studied. The Study explored that mining primarily responsible for land degradation. Which lead to food and agriculture losses. Several other factors like blasting, pollution, hunting, deforestation, habitat loss was also observed. Deforestation surfaced one of the major causes for extinction of fauna in the said region. preemptive measures are needed to seize the man-made catastrophe.
Resumo A mineração é vital para o sustento humano e um setor crucial na economia do Estado. No entanto, seus impactos sobre o meio ambiente e a biodiversidade não podem ser subestimados, visto serem potentes para atrair a atenção do governo. O meio ambiente e a vida selvagem estão sujeitos aos impactos prejudiciais da mineração e de suas atividades relacionadas. Neste estudo, os distritos, nomeadamente Mardan e Mohmand, foram selecionados no que diz respeito aos impactos da mineração. A avaliação foi realizada em animais selvagens afetados negativamente pelo setor de mineração. A fauna tem sido observada atentamente para trazer os riscos calculados e a percepção de ameaça à vida selvagem regional. Um total de nove espécies de mamíferos, 21 espécies de pássaros, foi registrado no Distrito Mardan. Enquanto no Distrito Mohmand, duas espécies de mamíferos, nove espécies de pássaros e quatro espécies de répteis foram estudadas. O estudo explorou essa mineração que é principalmente responsável pela degradação do solo, acarretando perdas de alimentos e na agricultura. Vários outros fatores como explosões, poluição, caça, desmatamento, perda de habitat também foram observados. O desmatamento veio à tona como uma das principais causas de extinção da fauna da região, e tem-se que medidas preventivas são necessárias para dimensionar a catástrofe provocada pelo homem.
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Esta investigación aborda la protesta, los sujetos y sus características, así como las formas de acción colectiva disruptivas en el levantamiento popular de octubre de 2019 en Santiago de Chile. El objetivo es analizar y reflexionar, a partir de la constatación de la ausencia de un sujeto de la convocatoria de las protestas, el uso de las prácticas disruptivas en estas, tratando de problematizar su supuesta "espontaneidad". La metodología se basa en una perspectiva cualitativa y entrevistas en profundidad a intelectuales y actores de la protesta. A modo de conclusión, la protesta, lejos de ser "espontánea", debe interpretarse como resultado de los repertorios de acción conocidos e innovaciones, así como de redes informales de cooperación, en que la acción colectiva disruptiva fue dominante.
This research addresses the protest, the subjects and their characteristics, as well as the forms of disruptive collective action in the popular uprising of October 2019 in Santiago de Chile. The objective is to analyze and reflect about the absence of a predetermined subject calling for the protests, the use of disruptive practices in them, and discussing their presumed "spontaneity". The methodology is based on a qualitative perspective and indepth interviews with academics and participants in the protest. My argument is that the protest, far from being "spontaneous", should be interpreted as the result of known repertoires of action and innovations, as well as informal networks of cooperation in which disruptive collective action was dominant.
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ObjectiveTo study the clinical efficacy of Shire Biqing pill in the treatment of rheumatoid arthritis （damp-heat obstruction syndrome） and its effect on the expression of serum osteoprotegerin （OPG）， nuclear factor-κB receptor activating factor ligand （RANKL）， and tumor necrosis factor-α （TNF-α）， and to explore its mechanism from the perspective of bone destruction. MethodPatients with rheumatoid arthritis （damp-heat obstruction syndrome） were randomly divided into two groups， with 36 patients in each group. The control group was treated with methotrexate tablets and celecoxib capsule， while the treatment group was treated with Shire Biqing pill based on the control group. The treatment period was 3 months. The pain visual analogue scale （VAS） score， joint tenderness number， joint swelling number， disease activity score （DAS28-ESR）， traditional Chinese medicine （TCM） symptom quantitative score， and related adverse reactions were recorded before and after treatment， and the peripheral serum OPG， RANKL， TNF-α， erythrocyte sedimentation rate （ESR）， and Creactive protein （CRP） were detected. ResultAfter treatment， the total effective rate was 88.57% （31/35） in the treatment group and 79.41% （27/34） in the control group. The total effective rate of the treatment group was higher than that of the control group （Z=-2.089， P<0.05）. The pain VAS score， joint tenderness number， joint swelling number， and DAS28-ESR of the two groups were significantly lower than those before treatment （P<0.05）， and the pain VAS score， joint tenderness number， joint swelling number， and DAS28-ESR of the treatment group were significantly better than those of the control group after treatment （P<0.05）. Compared with that before treatment， the TCM symptom quantitative score in the two groups decreased significantly （P<0.05）， and the decrease was more obvious in the treatment group than in the control group （P<0.05）. Compared with those before treatment， the levels of RANKL， TNF-α， ESR， and CRP in the two groups decreased and the level of OPG increased （P<0.05）， and the changes in the treatment group were more obvious that in the control group （P<0.05）. There were no serious adverse events or serious adverse reactions during this clinical trial. ConclusionShire Biqing pill can effectively improve the clinical symptoms of rheumatoid arthritis （damp-heat obstruction syndrome） with good safety. Shire Biqing pill effectively regulate the OPG/RANKL/RANK system and reduce the pro-inflammatory factor TNF-α， which may be its mechanism in the intervention in rheumatoid arthritis bone destruction.
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Abstract The Indian crested porcupine (Hystrix indica) is a vertebrate pest of agricultural lands and forest. The study was aimed to report the damage to local crops by the Indian crested porcupine (Hystrix indica) in the Muzaffarabad District. A survey was conducted to identify the porcupine-affected areas and assess the crop damage to the local farmers in district Muzaffarabad Azad Jammu and Kashmir (AJK) from May 2017 to October 2017. Around 19 villages were surveyed, and a sum of 191 semi-structured questionnaires was distributed among farmers. Crop damage was found highest in village Dhanni where a porcupine destroyed 175 Kg/Kanal of the crops. Regarding the total magnitude of crop loss, village Danna and Koomi kot were the most affected areas. More than half (51.8%) of the respondents in the study area suffered the economic loss within the range of 101-200$, and (29.8%) of the people suffered losses in the range of 201-300$ annually. Among all crops, maize (Zea mays) was found to be the most damaged crop ranging between 1-300 Kg annually. In the study area, porcupine also inflicted a lot of damages to some important vegetables, including spinach (Spinacia oleracea), potato (Solanum tuberosum) and onion (Allium cepa). It was estimated that, on average, 511Kg of vegetables are destroyed by porcupine every year in the agricultural land of Muzaffarabad. It was concluded that the Indian crested porcupine has a devastating effect on agriculture which is an important source of income and food for the local community. Developing an effective pest control strategy with the help of the local government and the Wildlife department could help the farmers to overcome this problem.
Resumo O porco-espinho de crista indiano (Hystrix indica) é uma praga vertebrada de terras agrícolas e florestais. No estudo atual, o dano às plantações locais pelo porco-espinho de crista indiano (Hystrix indica) foi relatado pela primeira vez no distrito de Muzaffarabad. O estudo foi projetado para investigar a perda econômica causada pelo porco-espinho de crista indiano (Hystrix indica) nos distritos de Muzaffarabad, Azad Jammu e Caxemira (AJK) de maio de 2017 a outubro de 2017. Um estudo baseado em pesquisa foi conduzido para identificar as áreas afetadas por porcos-espinhos e avaliar os danos às colheitas para os agricultores locais. Cerca de 19 aldeias foram pesquisadas e um total de 191 questionários semiestruturados foi distribuído entre os agricultores. Os danos às colheitas foram encontrados mais intensamente na aldeia Dhanni, onde um porco-espinho destruiu 175 kg / Kanal das colheitas. Em relação à magnitude total da perda de safra, as aldeias Danna e Koomi Kot foram as áreas mais afetadas. Mais da metade (51,8%) dos entrevistados na área de estudo sofreu perdas econômicas na faixa de 101-200 $, e 29,8% das pessoas sofreram perdas na faixa de 201-300 $ anualmente. Entre todas as culturas, o milho (Zea mays) foi considerado a cultura mais danificada, variando entre 1-300 kg anualmente. Na área de estudo, o porco-espinho também causou muitos danos a alguns vegetais importantes, incluindo espinafre (Spinacia oleracea), batata (Solanum tuberosum) e cebola (Allium cepa). Estimou-se que, em média, 511 kg de vegetais são destruídos pelo porco-espinho todos os anos nas terras agrícolas de Muzaffarabad. Concluiu-se que o porco-espinho de crista indiano tem um efeito devastador na agricultura, que é importante fonte de renda e alimento para a comunidade local. O desenvolvimento de uma estratégia eficaz de controle de pragas com a ajuda do governo local e do Departamento de Vida Selvagem pode ajudar os agricultores a superar esse problema.
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Humanos , Animales , Puercoespines , Pakistán , Productos Agrícolas , Agricultura , Animales SalvajesRESUMEN
Rheumatoid arthritis （RA） is a systemic chronic auto-inflammatory disease， characterized by infiltration of inflammatory cells， pannus formation， articular cartilage destruction， and bone matrix destruction. Therefore， improving articular cartilage destruction has an important impact on the treatment of RA. Chinese medicine has a good application effect in improving cartilage destruction of RA due to its characteristics of multiple components， multiple targets， high activity and low side effects. Based on this， the author reviewed relevant literature to summarize the relevant research and mechanism of Chinese medicine and its active components in improving RA cartilage destruction. The results showed that Chinese medicine and its active components can improve RA cartilage destruction by regulating inflammatory factors， phosphatidylinositol 3-kinase/protein kinase B， Wnt/β- catenin， nuclear factor-κB， mitogen-activated protein kinase， Janus kinase 2/signal transduction and activator of transcription 3/ vascular endothelial growth factor， microRNAs， fibroblastic synovial cells.
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The Indian crested porcupine (Hystrix indica) is a vertebrate pest of agricultural lands and forest. The study was aimed to report the damage to local crops by the Indian crested porcupine (Hystrix indica) in the Muzaffarabad District. A survey was conducted to identify the porcupine-affected areas and assess the crop damage to the local farmers in district Muzaffarabad Azad Jammu and Kashmir (AJK) from May 2017 to October 2017. Around 19 villages were surveyed, and a sum of 191 semi-structured questionnaires was distributed among farmers. Crop damage was found highest in village Dhanni where a porcupine destroyed 175 Kg/Kanal of the crops. Regarding the total magnitude of crop loss, village Danna and Koomi kot were the most affected areas. More than half (51.8%) of the respondents in the study area suffered the economic loss within the range of 101-200$, and (29.8%) of the people suffered losses in the range of 201-300$ annually. Among all crops, maize (Zea mays) was found to be the most damaged crop ranging between 1-300 Kg annually. In the study area, porcupine also inflicted a lot of damages to some important vegetables, including spinach (Spinacia oleracea), potato (Solanum tuberosum) and onion (Allium cepa). It was estimated that, on average, 511Kg of vegetables are destroyed by porcupine every year in the agricultural land of Muzaffarabad. It was concluded that the Indian crested porcupine has a devastating effect on agriculture which is an important source of income and food for the local community. Developing an effective pest control strategy with the help of the local government and the Wildlife department could help the farmers to overcome this problem.
O porco-espinho de crista indiano (Hystrix indica) é uma praga vertebrada de terras agrícolas e florestais. No estudo atual, o dano às plantações locais pelo porco-espinho de crista indiano (Hystrix indica) foi relatado pela primeira vez no distrito de Muzaffarabad. O estudo foi projetado para investigar a perda econômica causada pelo porco espinho de crista indiano (Hystrix indica) nos distritos de Muzaffarabad, Azad Jammu e Caxemira (AJK) de maio de 2017 a outubro de 2017. Um estudo baseado em pesquisa foi conduzido para identificar as áreas afetadas por porcos-espinhos e avaliar os danos às colheitas para os agricultores locais. Cerca de 19 aldeias foram pesquisadas e um total de 191 questionários semiestruturados foi distribuído entre os agricultores. Os danos às colheitas foram encontrados mais intensamente na aldeia Dhanni, onde um porco-espinho destruiu 175 kg / Kanal das colheitas. Em relação à magnitude total da perda de safra, as aldeias Danna e Koomi Kot foram as áreas mais afetadas. Mais da metade (51,8%) dos entrevistados na área de estudo sofreu perdas econômicas na faixa de 101-200 $, e 29,8% das pessoas sofreram perdas na faixa de 201-300 $ anualmente. Entre todas as culturas, o milho (Zea mays) foi considerado a cultura mais danificada, variando entre 1-300 kg anualmente. Na área de estudo, o porco-espinho também causou muitos danos a alguns vegetais importantes, incluindo espinafre (Spinacia oleracea), batata (Solanum tuberosum) e cebola (Allium cepa). Estimou-se que, em média, 511 kg de vegetais são destruídos pelo porco-espinho todos os anos nas terras agrícolas de Muzaffarabad. Concluiu-se que o porco-espinho de crista indiano tem um efeito devastador na agricultura, que é importante fonte de renda e alimento para a comunidade local. O desenvolvimento de uma estratégia eficaz de controle de pragas com a ajuda do governo local e do Departamento de Vida Selvagem pode ajudar os agricultores a superar esse problema.
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Control de Plagas/economía , Puercoespines , Plagas AgrícolasRESUMEN
Abstract The Indian crested porcupine (Hystrix indica) is a vertebrate pest of agricultural lands and forest. The study was aimed to report the damage to local crops by the Indian crested porcupine (Hystrix indica) in the Muzaffarabad District. A survey was conducted to identify the porcupine-affected areas and assess the crop damage to the local farmers in district Muzaffarabad Azad Jammu and Kashmir (AJK) from May 2017 to October 2017. Around 19 villages were surveyed, and a sum of 191 semi-structured questionnaires was distributed among farmers. Crop damage was found highest in village Dhanni where a porcupine destroyed 175 Kg/Kanal of the crops. Regarding the total magnitude of crop loss, village Danna and Koomi kot were the most affected areas. More than half (51.8%) of the respondents in the study area suffered the economic loss within the range of 101-200$, and (29.8%) of the people suffered losses in the range of 201-300$ annually. Among all crops, maize (Zea mays) was found to be the most damaged crop ranging between 1-300 Kg annually. In the study area, porcupine also inflicted a lot of damages to some important vegetables, including spinach (Spinacia oleracea), potato (Solanum tuberosum) and onion (Allium cepa). It was estimated that, on average, 511Kg of vegetables are destroyed by porcupine every year in the agricultural land of Muzaffarabad. It was concluded that the Indian crested porcupine has a devastating effect on agriculture which is an important source of income and food for the local community. Developing an effective pest control strategy with the help of the local government and the Wildlife department could help the farmers to overcome this problem.
Resumo O porco-espinho de crista indiano (Hystrix indica) é uma praga vertebrada de terras agrícolas e florestais. No estudo atual, o dano às plantações locais pelo porco-espinho de crista indiano (Hystrix indica) foi relatado pela primeira vez no distrito de Muzaffarabad. O estudo foi projetado para investigar a perda econômica causada pelo porco-espinho de crista indiano (Hystrix indica) nos distritos de Muzaffarabad, Azad Jammu e Caxemira (AJK) de maio de 2017 a outubro de 2017. Um estudo baseado em pesquisa foi conduzido para identificar as áreas afetadas por porcos-espinhos e avaliar os danos às colheitas para os agricultores locais. Cerca de 19 aldeias foram pesquisadas e um total de 191 questionários semiestruturados foi distribuído entre os agricultores. Os danos às colheitas foram encontrados mais intensamente na aldeia Dhanni, onde um porco-espinho destruiu 175 kg / Kanal das colheitas. Em relação à magnitude total da perda de safra, as aldeias Danna e Koomi Kot foram as áreas mais afetadas. Mais da metade (51,8%) dos entrevistados na área de estudo sofreu perdas econômicas na faixa de 101-200 $, e 29,8% das pessoas sofreram perdas na faixa de 201-300 $ anualmente. Entre todas as culturas, o milho (Zea mays) foi considerado a cultura mais danificada, variando entre 1-300 kg anualmente. Na área de estudo, o porco-espinho também causou muitos danos a alguns vegetais importantes, incluindo espinafre (Spinacia oleracea), batata (Solanum tuberosum) e cebola (Allium cepa). Estimou-se que, em média, 511 kg de vegetais são destruídos pelo porco-espinho todos os anos nas terras agrícolas de Muzaffarabad. Concluiu-se que o porco-espinho de crista indiano tem um efeito devastador na agricultura, que é importante fonte de renda e alimento para a comunidade local. O desenvolvimento de uma estratégia eficaz de controle de pragas com a ajuda do governo local e do Departamento de Vida Selvagem pode ajudar os agricultores a superar esse problema.
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Objective@#To analyze and evaluate the clinical application effect of bioceramic material mineral trioxide aggregate and iRoot BP plus on the formation of apical barrier in adult teeth with incomplete apical foramen.@*Methods@#A total of 200 permanent teeth with apical periodontitis whose apical foramen were not closed were randomly divided into two groups, and the apical barrier was prepared with MTA and iRoot BP plus, respectively. The operation time of MTA and iRoot BP plus and effects of different types of apical foramen destruction, lesion range of apical area, the filling of apical area and patients' age on the treatment success rate was analyzed and compared. @*Results@#The operation time of preparing apical barrier in iRoot BP plus group was shorter than that in MTA group, and the difference was statistically significant (P<0.05). However, different types of apical foramen destruction, lesion scope of apical area, filling of apical area and patients' age had no effect on the treatment success rate of the two groups (P>0.05). @*Conclusion@#The clinical effects of MTA and iRoot BP plus in the treatment of apical periodontitis of permanent teeth with unclosed apical foramen are similar, but the operation performance of iRoot BP plus is better.
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The present study investigated the mechanism of artesunate in the treatment of bone destruction in experimental rheumatoid arthritis(RA) based on transcriptomics and network pharmacology. The transcriptome sequencing data of artesunate in the inhibition of osteoclast differentiation were analyzed to obtain differentially expressed genes(DEGs). GraphPad Prism 8 software was used to plot volcano maps and heat maps were plotted through the website of bioinformatics. GeneCards and OMIM were used to collect information on key targets of bone destruction in RA. The DEGs of artesunate in inhibiting osteoclast differentiation and key target genes of bone destruction in RA were intersected by the Venny 2.1.0 platform, and the intersection target genes were analyzed by Gene Ontology(GO)/Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment. Finally, the receptor activator of nuclear factor-κB(RANKL)-induced osteoclast differentiation model and collagen-induced arthritis(CIA) model were established. Quantitative real time polymerase chain reaction(q-PCR), immunofluorescence, and immunohistochemistry were used to verify the pharmacological effect and molecular mechanism of artesunate in the treatment of bone destruction in RA. In this study, the RANKL-induced osteoclast differentiation model in vitro was established and intervened with artesunate, and transcriptome sequencing data were analyzed to obtain 744 DEGs of artesunate in inhibiting osteoclast differentiation. A total of 1 291 major target genes of bone destruction in RA were obtained from GeneCards and OMIM. The target genes of artesunate in inhibiting osteoclast differentiation and the target genes of bone destruction in RA were intersected to obtain 61 target genes of artesunate against bone destruction in RA. The intersected target genes were analyzed by GO/KEGG enrichment. According to the results previously reported, the cytokine-cytokine receptor interaction signaling pathway was selected for experimental verification. Artesunate intervention in the RANKL-induced osteoclast differentiation model showed that artesunate inhibited CC chemokine receptor 3(CCR3), CC chemokine receptor 1(CCR1) and leukemia inhibitory factor(LIF) mRNA expression in osteoclasts in a dose-dependent manner compared with the RANKL-induced group. Meanwhile, the results of immunofluorescence and immunohistochemistry showed that artesunate could dose-dependently reduce the expression of CCR3 in osteoclasts and joint tissues of the CIA rat model in vitro. This study indicated that artesunate regulated the CCR3 in the cytokine-cytokine receptor interaction signaling pathway in the treatment of bone destruction in RA and provided a new target gene for the treatment of bone destruction in RA.
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Ratas , Animales , Artritis Experimental/tratamiento farmacológico , Artesunato/uso terapéutico , Artritis Reumatoide/genética , Transcriptoma , Farmacología en Red , Osteoclastos , Receptores de Citocinas/uso terapéuticoRESUMEN
Objective@#To investigate the clinicopathological characteristics, imaging manifestations, genetic manifestations, diagnosis and treatment of juvenile hyaline fibromatosis.@*Methods @# A case of juvenile hyaline fibromatosis was reported, and the patient's clinical manifestations, imaging examinations, histopathological examinations, genetic changes and treatment were summarized and analyzed.@*Results @#Juvenile hyaloid fibromatosis is more common in infants and children. This patient had typical clinical and pathological manifestations, including posterior occipital masses, skin and subcutaneous nodules, gum hyperplasia, joint contractures, and joint osteolytic lesions. The histopathological lesions were characterized by the proliferation of spindle cells in the tissue accompanied by a large amount of amorphous transparent matrix. Genetic testing was performed to confirm an ANTXR2 gene mutation, consistent with the known genetic changes of juvenile hyaline fibromatosis. The 6-month follow-up of the patient showed that there was no obvious recurrence after resection of the gum and facial mass. In addition to surgery, the treatment of this disease requires multidisciplinary symptomatic treatment combined with rehabilitation and supportive treatment to achieve a better prognostic effect.@*Conclusion@# Juvenile hyaline fibromatosis is a rare nonneoplastic autosomal recessive genetic disease. Mutations in the ANTXR2 gene lead to disorders of collagen synthesis and metabolism in the tissues and further cause subcutaneous nodules, gingival hyperplasia, joint contractures and bone dissolution.
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Pancreatic adenocarcinoma (PAAD) is one of the most lethal malignancies. Although gemcitabine (GEM) is a standard treatment for PAAD, resistance limits its application and therapy. Secoemestrin C (Sec C) is a natural compound from the endophytic fungus Emericella, and its anticancer activity has not been investigated since it was isolated. Our research is the first to indicate that Sec C is a broad-spectrum anticancer agent and could exhibit potently similar anticancer activity both in GEM-resistant and GEM-sensitive PAAD cells. Interestingly, Sec C exerted a rapid growth-inhibiting effect (80% death at 6 h), which might be beneficial for patients who need rapid tumor shrinkage before surgery. Liquid chromatography/mass spectrometry and N-acetyl-l-cysteine (NAC) reverse assays show that Sec C sulfates cysteines to disrupt disulfide-bonds formation in endoplasmic reticulum (ER) proteins to cause protein misfolding, leading to ER stress and disorder of lipid biosynthesis. Microarray data and subsequent assays show that ER stress-mediated ER-associated degradation (ERAD) ubiquitinates and downregulates YAP to enhance ER stress via destruction complex (YAP-Axin-GSK-βTrCP), which also elucidates a unique degrading style for YAP. Potent anticancer activity in GEM-resistant cells and low toxicity make Sec C a promising anti-PAAD candidate.
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Objective:To analyze the serum levels of integrin-associated proteins (CD47) in patients with rheumatoid arthritis (RA), and to explore its association with disease activity and bone destruction in RA.Methods:Serum and clinical data were collected from 65 RA patients and 25 healthy subjects. RA patients were grouped into low, moderate, and high bone erosion groups according to 7-joint ultrasonography score (US7). The levels of serum CD47, thrombospondin-1 (TSP-1) and receptor activator of nuclear factor-κB ligand (RANKL) were measured by enzyme-linked immunosorbnent assay (ELISA) in patients with RA and healthy subjects. The statistical analysis was carried out with independent t-test, analysis of variance, nonparametric rank sum test, pearson or Spearman correlation and logistic regression. Results:① The Serum levels of CD47, TSP-1, and RANKL were higher in the RA group than in the healthy controls ( P<0.01). ② In RA patients, serum CD47 level was positively correlated with disease course ( r=0.301, P<0.05), C-reactionprotein (CRP)( r=0.316, P<0.05), number of tender joints (TJC) ( r=0.254, P<0.05), number of swollen joints (SJC) ( r=0.316, P<0.05), disease activity score in 28 joints (DAS28) ( r=0.255, P<0.05), RANKL ( r=0.252, P<0.05) and TSP-1 ( r=0.260, P<0.05). Serum TSP-1 level was positively correlated with CRP ( r=0.299, P<0.05), TJC ( r=0.335, P<0.01), DAS28 ( r=0.315, P<0.05), RANKL ( r=0.305, P<0.05). ③ The disease course [ OR(95% CI)=1.048(1.033, 1.017)] and TSP-1 [ OR(95% CI)=1.013(1.000, 1.026)] were independently relevant factors affecting bone destruction. Conclusion:CD47 levels is significantly higher in RA patients than in healthy controls, and is associated with disease activity and bone destruction. CD47 may be involved in the bone destruction process of RA by acting on TSP-1.
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Objective:To investigate the effect of vancomycin (Vm)-loaded microbubbles (MBs) combined with ultrasound targeted microbubble destruction (UTMD) technique on the morphological structure, thickness and bacterial viability of methicillin-resistant Staphylococcus aureus (MRSA) biofilms.Methods:Vm-MBs were prepared by thin film hydration. Sterile coverslips in a diameter of 13 mm were placed in 24-well plates to construct in vitro biofilm models using MRSA as the test strain, and the biofilm morphology was observed by naked eye and light microscopy after crystal violet staining. LIVE/DEAD, SYTO59 and DIL were used to stain biofilms and MBs, respectively. After staining, the biofilm morphology and position of the biofilm in relation to MBs were observed using laser confocal scanning microscopy. The biofilms were divided into control group, Vm group, Vm-MBs group, UTMD group and Vm-MBs+UTMD group according to the random number table method, with 9 samples in each group. After biofilms of each group were treated accordingly for 24 hours, the morphological and structural changes of biofilms in each group were observed using laser confocal scanning microscopy and scanning electron microscopy following LIVE/DEAD staining; the difference in biofilm density in each group was measured with the aid of an enzyme marker following crystal violet staining; the difference in biofilm thickness and bacterial viability in each group were observed by laser confocal scanning microscopy. Results:The prepared Vm-MBs met the experimental requirements. The constructed biofilm model observed by naked eye, light microscopy and laser confocal scanning microscopy showed that the biofilm structure was dense with a relatively uniform thickness of (13.8±0.2)nm, a small amount of dead bacteria inside the membrane and the percentage of live bacteria of (94.9±0.3)%. Laser confocal scanning microscopy showed that MBs could penetrate into deeper layers of biofilms. After the respective treatment was given to each group for 24 hours, Laser confocal scanning microscopy and scanning electron microscopy following LIVE/DEAD staining showed that the biofilm morphological structure was most significantly disrupted in Vm-MBs+UTMD group compared to control, Vm, Vm-MBs and UTMD groups. In Vm-MBs+UTMD group, a large number of dead bacteria was observed, with only a few scattered planktonic bacteria and irregular changes in cell membrane morphology. Crystal violet staining showed that the biofilm density was significantly lower in Vm-MBs+UTMD group compared to control group ( P<0.05), while the differences between Vm, Vm-MBs and UTMD groups were not statistically significant (all P>0.05). Laser confocal microscopy showed that the biofilm thickness was thinner in Vm-MBs, UTMD and Vm-MBs+UTMD groups compared to control group (all P<0.05), with no significant difference between Vm group and control group ( P>0.05) and that the biofilm thickness was thinner in Vm-MBs+UTMD group compared to Vm, Vm-MBs and UTMD groups (all P<0.01), with no significant differences between the other groups (all P>0.05). Bacterial activity in Vm, Vm-MBs, UTMD and Vm-MBs+UTMD groups was significantly lower than that in control group (all P<0.01), with lower in Vm-MBs+UTMD group compared to Vm, Vm-MBs and UTMD groups (all P<0.01), but without significant difference between the other groups (all P>0.05). Conclusion:Vm-MBs combined with UTMD technology can effectively destroy the biofilm morphological structure to reduce biofilm thickness. Meanwhile, Vm-MBs combined with UTMD technology can release antibiotics and significantly decrease bacterial viability to improve antibiotic bactericidal efficacy.
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Objective:To investigate the effect of Duhuo Jisheng Decoction on early cartilage destruction markers in patients with rheumatoid arthritis with kidney-qi deficiency and cold syndrome.Methods:A total of 64 patients with rheumatoid arthritis in our hospital from March 2019 to March 2020 who met the inclusion criteria were divided into 2 groups, according to the random number table method, with 32 in each group. The control group was given conventional western medicine therapy, and the observation group was given Duhuo Jisheng decoction on the basis of the control group. Both groups were treated for 8 weeks. TCM syndrome scores were performed before and after treatment, serum CRP, IL-6, cartilage oligosaccharide protein (COMP) and β-catenin were detected by ELISA method, and adverse eventns during treatment were observed and compared. The clinical efficacy was evaluated.Results:The total effective rate was 87.5% (28/32) in the observation group and 65.6% (21/32) in the control group, and the difference between the two groups was statistically significant ( χ2=4.27, P=0.039). After treatment, the main symptoms, secondary symptoms and tongue and pulse scores of the observation group were significantly lower than those in the control group ( t=7.11, 3.11, 2.41, P<0.01 or P<0.05); serum CRP and IL-6 levels were significantly lower than those in the control group ( t=3.04, 4.56, P<0.01); serum COMP [(12.37±1.68) μg/L vs. (14.24±1.88) μg/L, t=4.20], β-catenin [(1.35±0.24) μg/L vs. (1.68±0.31) μg/L, t=4.76] levels were significantly lower than those in the control group ( P<0.01). During the treatment, the incidence of adverse events was 25.0% (8/32) in the observation group and 18.8% (6/32) in the control group, and there was no significant difference between the two groups ( χ2=0.37, P=0.546). Conclusion:The Duhuo Jisheng Decoction can help to reduce the levels of inflammatory cytokines and early cartilage destruction markers in patients with rheumatoid arthritis, and improve the clinical efficacy safely.
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O presente trabalho parte da ideia de caracterizar o disruptivo no pensamento freudiano. Como ponto de partida, toma o trabalho de 1914, À guisa de introdução ao narcisismo, por reconhecer nele um momento primeiro de ruptura na teoria pulsional vigente: libido do Eu versus libido objetal. Durante o trajeto, sinaliza marcas desse processo e direciona-se para o disruptivo que se instala em termos metapsicológicos, com maior consistência, com o advento da pulsão de morte. A pulsão de destruição, como agente do disruptivo em sua relação com Eros, desenhará caminhos que permitem vislumbrar destinos tanáticos ou criativos. Com essa concepção metapsicológica como indicador, busca-se refletir a respeito da interação entre o disruptivo da pandemia viral e o disruptivo da virulência do racismo e seus desdobramentos criativos na efetivação, pelo coletivo da humanidade, de posturas antirracistas. Tal contexto alberga uma interrogação pontual: como a pandemia, em seu efeito disruptivo, está relacionada com a percepção em toda a sua sensorialidade, em grande escala, de norte a sul, daquilo que mantinha-se parcialmente silencioso e invisível, o racismo? (AU)
The present article begins from the idea of characterize the disruptive in the freudian's thoughts. Is takes as a starter point the work of 1914, On narcissism: an introduction, for recognize it as a first moment of rupture in the current drive theory: self libido versus object libido. In this path, it signals marks of this process and orientate to the disruptive that develops in metapsychological terms, with great consistency, with the advent of the death drive. The destruction drive, as a disruptive agent, in its relation with Eros, will draw paths that allow glimpse its tanatic fate or criative fate. From this metapsychological conception, as an indicator, seeks to reflect the interaction between the disruptive in the viral pandemic and the disruptive in the racism virulence, and its criatives developments in the effectuation of anti-racist postures, by the humanity collective. Context that holds an punctual interrogation: how the pandemic, with its disruptive effect, is related with the perception in all its sensoriality, in big scale, from north to south, with what was, in part, silence and inivisible: the racism? (AU)
El objetivo inicial del presente trabajo es caracterizar lo disruptivo en el pensamiento freudiano. Se toma como punto de partida el célebre texto de 1914 Introducción del narcisismo por reconocer en él un primer momento de ruptura en la teoría pulsional vigente hasta ese momento, que distinguía la libido del Yo y la libido de objeto. En ese recorrido, se irán señalando marcas de dicho proceso orientándose hacia lo disruptivo, que se instalará con mayor consistencia, en términos metapsicológicos, con el advenimiento de la pulsión de muerte. La pulsión de destrucción, como agente de lo disruptivo, en su relación con Eros, trazará caminos que permiten vislumbrar sus destinos tanáticos o creativos. Tomando esa concepción metapsicológica como indicador, busco reflejar la interacción entre lo disruptivo de la pandemia viral y lo disruptivo de la virulencia del racismo, así como sus desdoblamientos creativos en la adopción de posturas antirracistas por parte del colectivo humano. En este contexto se plantea una interrogación puntual: ¿cómo la pandemia, con su efecto disruptivo, está relacionada con la percepción en toda su sensorialidad, en gran escala, de norte a sur, de aquello que, en parte, se mantenía silencioso e invisible, el racismo?
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Pandemias/prevención & control , Racismo/psicología , Rotura/psicología , Virulencia , Impulso (Psicología) , NarcisismoRESUMEN
Objective:To investigate the effects of ultrasound microbubble-mediated RasGAP SH3-binding protein 1 (G3BP1) transfection on the proliferation and migration of human liver cancer HepG2 cells.Methods:HepG2 cells were treated with ultrasound targeted microbubble destruction (UTMD) technology-mediated si-G3BP1. The expression of G3BP1 in HepG2 cell lines was detected by Western blot, and the silencing efficiency was analyzed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot. HepG2 cell proliferation and migration were analyzed by flow cytometry, methyl thiazolyl tetrazolium (MTT) , EdU staining, colony formation experiment, wound healing experiment, Transwell experiment and Western blot.Results:After silencing G3BP1 in HepG2 cells, its mRNA and protein levels were significantly reduced (1.01±0.03 vs 0.27±0.03, 1.02±0.01 vs 0.33±0.04) ; UTMD-mediated si-G3BP1 could significantly reduce the proliferation rate (31.49±3.09 vs 12.51±1.02) , proliferation activity (1.20±0.13 vs 0.46±0.31) , EdU-positive cell rate (99.23±1.01 vs 36.75±4.03) , colony formation rate (96.45±1.21 vs 32.67±2.62) , scratch healing rate (97.58±1.04 vs 42.33±2.56) , migration rate (94.28±2.33 vs 39.36±2.51) and Ki67, Cyclin D1, Vimentin protein levels, increase E-cadherin protein levels.Conclusion:UTMD-mediated si-G3BP1 can inhibit the proliferation and migration of human liver cancer HepG2 cells.
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For rheumatoid arthritis， glucocorticoids or immunosuppressive agents are currently used in clinical treatment， but long-term use of these drugs has large side effect on humans， and immunosuppressive agents are expensive. To a certain extent， its wide application is limited. The treatment of rheumatoid arthritis with traditional Chinese medicine（TCM） has a long history and little toxic and side effect， but its specific mechanism of action needs further exploration. The process of autophagy is an active biological process in which cells themselves are stimulated by the outside world through intracellular signal transduction to maintain a stable internal environment. Its abnormality is involved in the occurrence of many diseases. At present， studies have shown that abnormal autophagy is closely related to the occurrence and development of rheumatoid arthritis， which can interfere with the pathological changes of RA pannus formation， synovial inflammation and bone destruction and affect the disease process. In recent years， many studies have found that traditional Chinese medicine and its active ingredients can affect the pathological development of rheumatoid arthritis by regulating autophagy. This article investigates the relevant literature on the intervention of rheumatoid arthritis by regulating autophagy through using TCM， with a view to providing new ideas for basic research， new drug development and clinical treatment of rheumatoid arthritis.
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@#BACKGROUND: To investigate the clinical characteristics and risk factors of human immunodeficiency virus (HIV)-negative patients with Talaromyces marneffei (T. marneffei) infection. METHODS: We retrospectively collected the clinical information of HIV-negative patients with T. marneffei infection from January 1, 2010 to June 30, 2019, and analyzed the related risk factors of poor prognosis. RESULTS: Twenty-five cases aging 22 to 79 years were included. Manifestations of T. marneffei infection included fever, cough, dyspnea, chest pain or distress, lymphadenopathy, ear, nose, and throat (ENT) and/or skin lesions, bone or joint pain, edema and pain in the lower extremities, digestive symptoms, icterus, malaise, and hoarseness. Two cases had no comorbidity, while 23 cases suffered from autoimmune disease, pulmonary disease, cancer, and other chronic diseases. Sixteen cases had a medication history of glucocorticoids, chemotherapy or immunosuppressors. Pulmonary lesions included interstitial infiltration, nodules, atelectasis, cavitary lesions, pleural effusion or hydropneumothorax, bronchiectasis, pulmonary fibrosis, pulmonary edema, and consolidation. The incidence of osteolytic lesions was 20%. Eight patients received antifungal monotherapy, and 11 patients received combined antifungal agents. Fifteen patients survived and ten patients were dead. The Cox regression analysis showed that reduced eosinophil counts, higher levels of blood urea nitrogen (BUN), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactic dehydrogenase (LDH), myoglobin (Mb), procalcitonin (PCT), and galactomannan were related to poor prognosis (hazard ratio [HR]>1, P<0.05). CONCLUSIONS: Bone destruction is common in HIV-negative patients with T. marneffei infection. Defective cell-mediated immunity, active infection, multiple system, and organ damage can be the risk factors of poor prognosis.