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BACKGROUND: Despite the functions of TLRs in the parasitic infections have been extensively reported, few studies have addressed the role of TLR3 in the immune response to Schistosoma japonicum infections. The aim of this study was to investigate the properties of TLR3 in the liver of C57BL/6 mice infected by S. japonicum. METHODS: The production of TLR3+ cells in CD4+T cells (CD4+CD3+), CD8+T cells (CD8+CD3+), γδT cells (γδTCR+CD3+), NKT cells (NK1.1+CD3+), B cells (CD19+CD3-), NK (NK1.1-CD3+) cells, MDSC (CD11b+Gr1+), macrophages (CD11b+F4/80+), DCs (CD11c+CD11b+) and neutrophils (CD11b+ Ly6g+) were assessed by flow cytometry. Sections of the liver were examined by haematoxylin and eosin staining in order to measure the area of granulomas. Hematological parameters including white blood cell (WBC), red blood cell (RBC), platelet (PLT) and hemoglobin (HGB) were analyzed. The levels of ALT and AST in the serum were measured using biochemical kits. The relative titers of anti-SEA IgG and anti-SEA IgM in the serum were measured by enzyme-linked immunosorbent assay (ELISA). CD25, CD69, CD314 and CD94 molecules were detected by flow cytometry. RESULTS: Flow cytometry results showed that the expression of TLR3 increased significantly after S. japonicum infection (P < 0.05). Hepatic myeloid and lymphoid cells could express TLR3, and the percentages of TLR3-expressing MDSC, macrophages and neutrophils were increased after infection. Knocking out TLR3 ameliorated the damage and decreased infiltration of inflammatory cells in infected C57BL/6 mouse livers.,The number of WBC was significantly reduced in TLR3 KO-infected mice compared to WT-infected mice (P < 0.01), but the levels of RBC, platelet and HGB were significantly increased in KO infected mice. Moreover, the relative titers of anti-SEA IgG and anti-SEA IgM in the serum of infected KO mice were statistically decreased compared with the infected WT mice. We also compared the activation-associated molecules expression between S.japonicum-infected WT and TLR3 KO mice. CONCLUSIONS: Taken together, our data indicated that TLR3 played potential roles in the context of S. japonicum infection and it may accelerate the progression of S. japonicum-associated liver pathology.
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Schistosoma japonicum , Animais , Camundongos , Schistosoma japonicum/metabolismo , Receptor 3 Toll-Like/metabolismo , Camundongos Endogâmicos C57BL , Imunoglobulina G , Imunoglobulina MRESUMO
CD103 is an important marker of tissue-resident memory T cells (TRM) which play important roles in fighting against infection. However, the immunological characteristics of CD103+ T cells are not thoroughly elucidated in the liver of mouse infected with Plasmodium. Six- to eight-week-old C57BL/6 mice were infected with Plasmodium yoelii nigeriensis NSM. Mice were sacrificed on 12-16 days after infection and the livers were picked out. Sections of the livers were stained, and serum aspartate aminotransferase (AST) and alanine transaminase (ALT) levels were measured. Moreover, lymphocytes in the liver were isolated, and the expression of CD103 was determined by using qPCR. The percentage of CD103 on different immune cell populations was dynamically observed by using flow cytometry (FCM). In addition, the phenotype and cytokine production characteristics of CD103+CD8+ Tc cell were analyzed by using flow cytometry, respectively. Erythrocyte stage plasmodium infection could result in severe hepatic damage, a widespread inflammatory response and the decrease of CD103 expression on hepatic immune cells. Only CD8+ Tc and γδT cells expressed higher levels of CD103 in the uninfected state.CD103 expression in CD8+ Tc cells significantly decreased after infection. Compared to that of CD103- CD8+ Tc cells, CD103+ CD8+ Tc cells from the infected mice expressed lower level of CD69, higher level of CD62L, and secreted more IL-4, IL-10, IL-17, and secreted less IFN-γ. CD103+CD8+ Tc cells might mediate the hepatic immune response by secreting IL-4, IL-10, and IL-17 except IFN-γ in the mice infected with the erythrocytic phase plasmodium, which could be involved in the pathogenesis of severe liver damage resulted from the erythrocytic phase plasmodium yoelii nigeriensis NSM infection.
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Malária , Plasmodium yoelii , Animais , Camundongos , Linfócitos T CD8-Positivos/metabolismo , Interleucina-10/metabolismo , Interleucina-17 , Interleucina-4 , Fígado , Malária/imunologia , Malária/metabolismo , Camundongos Endogâmicos C57BLRESUMO
This study aimed to characterize the expression status and potentially mechanistic involvement of SNHG7 in pituitary adenoma. Relative expression of SNHG7 and miR-449a was analyzed by real-time PCR. Cell viability was measured with Cell Counting Kit-8 (CCK-8). Cell apoptosis was determined by PI/Annexin V double staining followed by flow cytometry analysis. Cell invasion and migration were analyzed by wound healing and transwell assays, respectively. The regulatory action of miR-449a on SNHG7 was interrogated by luciferase reporter assay. We also investigated the pro-tumor activity of SNHG7 with the MMQ xenograft tumor mouse model. We identified the aberrant up-regulation of SNHG7 in pituitary adenoma both in vivo and in vitro, which associated with poor survival outcome. siRNA-mediated SNHG7-knockdown decreased cell viability, increased apoptosis and compromised migration and invasion. We further predicted and validated that SNHG7 negatively regulated miR-449a via sponging. Concurrent inhibition of miR-449a restored cell viability, apoptosis, migration and invasion influenced by SNHG7-deficiency. Most importantly, we demonstrated that SNHG7-silencing delayed xenograft tumor progression, which was accompanied with increased miR-449a and decreased Ki67 intensity. Our study highlighted the essential oncogenic properties of the SNHG7/miR-449a axis in pituitary adenoma.
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Adenoma/metabolismo , MicroRNAs/metabolismo , Hipófise/metabolismo , Neoplasias Hipofisárias/metabolismo , RNA Longo não Codificante/metabolismo , Adenoma/genética , Adenoma/patologia , Animais , Apoptose/fisiologia , Linhagem Celular , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Sobrevivência Celular/fisiologia , Progressão da Doença , Humanos , MicroRNAs/genética , Hipófise/patologia , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/patologia , RNA Longo não Codificante/genética , RatosRESUMO
BACKGROUND: Pancreatic cancer, one of the most aggressive malignancies, ranks the fourth cause of cancer-related death worldwide. Aberrantly expressed long non-coding RNAs (lncRNAs) functioned as oncogenes or tumor suppressors in pancreatic cancer. This study aimed to determine the expression of lncRNA DLX6 antisense RNA 1 (DLX6-AS1) in pancreatic cancer tissues and to explore the DLX6-AS1-related pathway in pancreatic cancer. MATERIALS AND METHODS: The gene expression levels were determined by quantitative real-time PCR, and protein expression levels were determined by western blot assay. CCK-8 assay, colony formation assay and Transwell migration and invasion assays were used to examine cell proliferation, migration and invasion. Luciferase reporter assay was used to confirm the binding between DLX6-AS1and its potential targets. In vivo study used the mouse xenograft model to test the anti-tumor effect of DLX6-AS1 knockdown. RESULTS: The high expression of DLX6-AS1 was observed in pancreatic cancer tissues, and high expression of DLX6-AS1 was positively correlated with larger tumor size, advanced TNM stage and lymph node metastasis. Knockdown of DLX6-AS1 dramatically impaired cancer cell proliferation, migration and invasion. MiR-181b was the downstream target of DLX6-AS1. Knockdown of miR-181b reversed the suppression of cell viability, migration and invasion abilities caused by DLX6-AS1 knockdown. MiR-181b was found to target Zinc finger E-box-binding homeobox 2 and to modulate epithelial-mesenchymal transition. Furthermore, DLX6-AS1 knockdown inhibited tumor growth and tumor metastasis in vivo. CONCLUSION: Collectively, our data suggested that DLX6-AS1 promotes cancer cell proliferation and invasion by attenuating the endogenous function of miR-181b in pancreatic cancer.
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Mild traumatic brain injury (mTBI)-induced post-traumatic headache (PTH) is a pressing public health concern and leading cause of disability worldwide. Although PTH is often accompanied by neurological disorders, the exact underlying mechanism remains largely unknown. Identifying potential biomarkers may prompt the diagnosis and development of effective treatments for mTBI-induced PTH. In this study, a mouse model of mTBI-induced PTH was established to investigate its effects on cerebral structure and function during short-term recovery. Results indicated that mice with mTBI-induced PTH exhibited balance deficits during the early post-injury stage. Metabolic kinetics revealed that variations in neurotransmitters were most prominent in the cerebellum, temporal lobe/cortex, and hippocampal regions during the early stages of PTH. Additionally, variations in brain functional activities and connectivity were further detected in the early stage of PTH, particularly in the cerebellum and temporal cortex, suggesting that these regions play central roles in the mechanism underlying PTH. Moreover, our results suggested that GABA and glutamate may serve as potential diagnostic or prognostic biomarkers for PTH. Future studies should explore the specific neural circuits involved in the regulation of PTH by the cerebellum and temporal cortex, with these two regions potentially utilized as targets for non-invasive stimulation in future clinical treatment.
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Modelos Animais de Doenças , Cefaleia Pós-Traumática , Animais , Camundongos , Cefaleia Pós-Traumática/etiologia , Cefaleia Pós-Traumática/fisiopatologia , Masculino , Encéfalo/metabolismo , Encéfalo/patologia , Concussão Encefálica/complicações , Concussão Encefálica/fisiopatologia , Camundongos Endogâmicos C57BLRESUMO
Although the functions of programmed death-1 (PD-1) on αß T cells have been extensively reported, a role for PD-1 in regulating γδT cell function is only beginning to emerge. Here, we investigated the phenotypic and functional characteristics of PD-1-expressing γδT cells, and the molecular mechanism was also explored in the Plasmodium yoelii nigeriensis (P. yoelii NSM)-infected mice. Flow cytometry and single-cell RNA sequencing (scRNA-seq) were performed. An inverse agonist of RORα, SR3335, was used to investigate the role of RORα in regulating PD-1+ γδT cells. The results indicated that γδT cells continuously upregulated PD-1 expression during the infection period. Higher levels of CD94, IL-10, CX3CR1, and CD107a; and lower levels of CD25, CD69, and CD127 were found in PD-1+ γδT cells from infected mice than in PD-1- γδT cells. Furthermore, GO enrichment analysis revealed that the marker genes in PD-1+ γδT cells were involved in autophagy and processes utilizing autophagic mechanisms. ScRNA-seq results showed that RORα was increased significantly in PD-1+ γδT cells. GSEA identified that RORα was mainly involved in the regulation of I-kappaB kinase/NF-κB signaling and the positive regulation of cytokine production. Consistent with this, PD-1-expressing γδT cells upregulated RORα following Plasmodium yoelii infection. Additionally, in vitro studies revealed that higher levels of p-p65 were found in PD-1+ γδT cells after treatment with a RORα selective synthetic inhibitor. Collectively, these data suggest that RORα-mediated attenuation of NF-κB signaling may be fundamental for PD-1-expressing γδT cells to modulate host immune responses in the spleen of Plasmodium yoelii nigeriensis-infected C57BL/6 mice, and it requires further investigation.
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Malária , Plasmodium yoelii , Receptor de Morte Celular Programada 1 , Baço , Animais , Plasmodium yoelii/imunologia , Receptor de Morte Celular Programada 1/metabolismo , Malária/imunologia , Malária/parasitologia , Camundongos , Baço/imunologia , Baço/parasitologia , Feminino , Transdução de Sinais/imunologia , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Receptores de Antígenos de Linfócitos T gama-delta/imunologiaRESUMO
This study is to evaluate the feasibility of deep learning (DL) models in the multiclassification of reflux esophagitis (RE) endoscopic images, according to the Los Angeles (LA) classification for the first time. The images were divided into three groups, namely, normal, LA classification A + B, and LA C + D. The images from the HyperKvasir dataset and Suzhou hospital were divided into the training and validation datasets as a ratio of 4 : 1, while the images from Jintan hospital were the independent test set. The CNNs- or Transformer-architectures models (MobileNet, ResNet, Xception, EfficientNet, ViT, and ConvMixer) were transfer learning via Keras. The visualization of the models was proposed using Gradient-weighted Class Activation Mapping (Grad-CAM). Both in the validation set and the test set, the EfficientNet model showed the best performance as follows: accuracy (0.962 and 0.957), recall for LA A + B (0.970 and 0.925) and LA C + D (0.922 and 0.930), Marco-recall (0.946 and 0.928), Matthew's correlation coefficient (0.936 and 0.884), and Cohen's kappa (0.910 and 0.850), which was better than the other models and the endoscopists. According to the EfficientNet model, the Grad-CAM was plotted and highlighted the target lesions on the original images. This study developed a series of DL-based computer vision models with the interpretable Grad-CAM to evaluate the feasibility in the multiclassification of RE endoscopic images. It firstly suggests that DL-based classifiers show promise in the endoscopic diagnosis of esophagitis.
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Aprendizado Profundo , Esofagite Péptica , Ácido Glicirretínico , Humanos , Esofagite Péptica/diagnóstico , Los Angeles , Fontes de Energia ElétricaRESUMO
Objective To investigate the effect of T cell immunoreceptor with Ig and ITIM domains (TIGIT) on the function of CD8+ T cells in the lungs of Plasmodium infected mice. Methods The lungs of the mice infected with Plasmodium yoelii were isolated, weighed and photographed after 12 days' infection. After dissolution, lung lymphocytes were isolated, counted and stained, and then the contents of CD8+ and TIGIT+CD8+ T cells were detected by flow cytometry. The expressions of L selectin (CD62L), CD69, programmed death 1 (PD-1), CD25, and C-X3-C motif chemokine receptor 1 (CX3CR1) on TIGIT+CD8+ T cells were detected by flow cytometry. After stimulation with phorbol 12-myristate 13-acetate (PMA) and ionomycin, the ability of TIGIT+CD8+T cells to secrete interferon γ(IFN-γ), interleukin 21 (IL-21), IL-4, IL-17, and IL-10 was detected. Results The body mass of mice with Plasmodium infection was reduced. The lungs became darker, and the ratio of the lung mass to body mass was significantly increased. Compared with the normal mice, the percentages and absolute quantity of CD8+ and TIGIT+CD8+ T cells in the lungs of the infected mice were significantly increased. The percentage of TIGIT+CD8+ T cells expressing CD62L in the infected group was significantly lower, while the percentage of the CD69, PD-1, and CX3CR1 cells were significantly higher than that of TIGIT+CD8+ T cells from the normal mice. The percentages of TIGIT+CD8+ T cells secreting IL-21, IL-4, IL-17 and IL-10 cells in the infected group were significantly lower. Conclusion The lung lesions from mice with Plasmodium infection are obvious, the numbers of TIGIT+CD8+ T cells increase, and these cells express a variety of activation-related molecules, but the ability to secrete cytokines is reduced.
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Malária , Plasmodium yoelii , Animais , Camundongos , Linfócitos T CD8-Positivos , Citocinas/metabolismo , Interferon gama/metabolismo , Interleucina-10/metabolismo , Interleucina-17/metabolismo , Interleucina-4/metabolismo , Pulmão/metabolismo , Malária/metabolismo , Plasmodium yoelii/metabolismo , Receptor de Morte Celular Programada 1/metabolismoRESUMO
Recently, there is a paucity of studies focus on the characteristics of myeloid cells which expressed γδTCR. The aim of this study was to observe the properties of γδTCR-expressing myeloid cells in the spleen of C57BL/6 mice infected by P. yoelii nigeriensis NSM. Haematoxylin-eosin (HE) staining was used to observe pathological changes in the spleens from infected mice. The differentially expressed genes (DEGs) between the infection and control groups were analyzed by RNA sequencing (RNA -seq). Flow cytometry (FCM) was used to evaluate the frequency of γδTCR+ cells and the characteristics of γδTCR+ cells in P. yoelii nigeriensis NSM-infected mice. Obvious infiltration of inflammatory were observed in the spleens from infected C57BL/6 mouse. The proportions of γδTCR+ cells and CD11b+ γδTCR+ cells from infected group were higher than that from normal group. CD11b+ γδTCR+ cells expressed high levels of activated-mediated genes and inflammatory-mediated genes. The heterogeneous pathway activities among CD11b+ γδTCR+ cells from normal and infected group were characterized. The oxidative phosphorylation, respiratory electron transport chain and leukocyte activation involved in immune response pathways were up-regulated, while the alpha-beta T cell activation and myeloid leukocyte migration pathways were down-regulated in infected mice. Importantly, Ly6c2 was higher expressed in CD11b+ γδTCR+ cells than Ly6g. Consistent with it, flow cytometry results revealed that a subset of Ly6C+ cells was higher than Ly6G+ cells in the spleen. Taken together, our data suggest the existence of a population of γδTCR-expressing myeloid cells and they might be multifunctional cells, which play a role in couse of Plasmodium infection.
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Malária , Células Mieloides , Plasmodium yoelii , Receptores de Antígenos de Linfócitos T gama-delta , Animais , Camundongos , Citometria de Fluxo , Camundongos Endogâmicos C57BL , Células Mieloides/metabolismo , Plasmodium yoelii/fisiologiaRESUMO
OBJECTIVE: Esophageal varix (EV) bleeding is a particularly serious complications of cirrhosis. Prediction of EV bleeding requires extensive endoscopy experience; it remains unreliable and inefficient. This retrospective cohort study evaluated the feasibility of using deep learning (DL) to predict the 12-month risk of EV bleeding based on endoscopic images. METHODS: Six DL models were trained to perform binary classification of endoscopic images of EV bleeding. The models were subsequently validated using an external test dataset, then compared with classifications performed by two endoscopists. RESULTS: In the validation dataset, EfficientNet had the highest accuracy (0.910), followed by ConvMixer (0.898) and Xception (0.875). In the test dataset, EfficientNet maintained the highest accuracy (0.893), which was better than the endoscopists (0.800 and 0.763). Notably, one endoscopist displayed higher recall (0.905), compared with EfficientNet (0.870). When their predictions were assisted by artificial intelligence, the accuracies of the two endoscopists increased by 17.3% and 19.0%. Moreover, statistical agreement among the models was dependent on model architecture. CONCLUSIONS: This study demonstrated the feasibility of using DL to predict the 12-month risk of EV bleeding based on endoscopic images. The findings suggest that artificial intelligence-aided diagnosis will be a useful addition to cirrhosis management.
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Aprendizado Profundo , Varizes Esofágicas e Gástricas , Humanos , Hemorragia Gastrointestinal/diagnóstico por imagem , Hemorragia Gastrointestinal/etiologia , Varizes Esofágicas e Gástricas/diagnóstico por imagem , Varizes Esofágicas e Gástricas/complicações , Inteligência Artificial , Estudos Retrospectivos , Endoscopia Gastrointestinal/efeitos adversos , Cirrose Hepática/diagnóstico , Cirrose Hepática/diagnóstico por imagemRESUMO
Interleukin 9 (IL-9) is an effective cytokine secreted by newly defined Th9 cells, which is involved in allergic and infectious diseases. In this study, lymphocytes were isolated from mesenteric lymph node (MLN), spleen, liver, lung, and Peyer's patches (PP) of C57BL/6 mice 5-6 weeks after S. japonicum infection, intracellular cytokine staining was done to detect the percentage of IL-9-producing CD4+ T cells. The qPCR and ELISA were used to verify the content of IL-9 in MLN. The population of IL-9-producing lymphocyte subset was identified by FACS. In addition, the dynamic changes and cytokine profiles of Th9 cells in the MLN of infected mice were detected by FACS. ELISA was used to detect IL-9 induced by soluble egg antigen (SEA) from isolated lymphocytes in mouse MLN. The results showed that the percentage of IL-9-secreting Th9 cells in the MLN of the infected mouse was higher than that in the spleen, liver, lung, or PP. Though CD8+ Tc cells, NKT cells, and γδT cells could secrete IL-9, CD4+ Th cells were the main source of IL-9 in S. japonicum-infected C57BL/6 mice (P < 0.05). The percentage of Th9 cells in MLN of infected mouse increased from week 3-4, and reached a peak at week 5-6, then began to decrease from week 7-8 (P < 0.05). Moreover, Th9 cells could also secrete a small amount of IL-4, IFN-γ, IL-5, and IL-10. Our results suggested a higher percentage of Th9 cells was induced in the MLN of S. japonicum-infected mice, which might play an important role in the early stage of S. japonicum-induced disease.
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Schistosoma japonicum , Esquistossomose Japônica , Animais , Camundongos , Esquistossomose Japônica/patologia , Interleucina-9 , Camundongos Endogâmicos C57BL , Linfonodos/patologiaRESUMO
Splenomegaly is a prominent clinical manifestation of malaria and the causes remain incompletely clear. Anemia is induced in malaria and extramedullary splenic erythropoiesis is compensation for the loss of erythrocytes. However, the regulation of extramedullary splenic erythropoiesis in malaria is unknown. An inflammatory response could facilitate extramedullary splenic erythropoiesis in the settings of infection and inflammation. Here, when mice were infected with rodent parasites, Plasmodium yoelii NSM, TLR7 expression in splenocytes was increased. To explore the roles of TLR7 in splenic erythropoiesis, we infected wild-type and TLR7 -/- C57BL/6 mice with P. yoelii NSM and found that the development of splenic erythroid progenitor cells was impeded in TLR7 -/- mice. Contrarily, the treatment of the TLR7 agonist, R848, promoted extramedullary splenic erythropoiesis in wild-type infected mice, which highlights the implication of TLR7 on splenic erythropoiesis. Then, we found that TLR7 promoted the production of IFN-γ that could enhance phagocytosis of infected erythrocytes by RAW264.7. After phagocytosis of infected erythrocytes, the iron metabolism of RAW264.7 was upregulated, evidenced by higher iron content and expression of Hmox1 and Slc40a1. Additionally, the neutralization of IFN-γ impeded the extramedullary splenic erythropoiesis modestly and reduced the iron accumulation in the spleen of infected mice. In conclusion, TLR7 promoted extramedullary splenic erythropoiesis in P. yoelii NSM-infected mice. TLR7 enhanced the production of IFN-γ, and IFN-γ promoted phagocytosis of infected erythrocytes and the iron metabolism of macrophages in vitro, which may be related to the regulation of extramedullary splenic erythropoiesis by TLR7.
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Malária , Baço , Camundongos , Animais , Baço/metabolismo , Eritropoese , Receptor 7 Toll-Like , Camundongos Endogâmicos C57BL , Interferon gama/uso terapêutico , Macrófagos/metabolismo , Ferro/metabolismoRESUMO
We used semi-quantitative grading of musculoskeletal ultrasound to evaluate wrist and hand lesions of subclinical synovitis, in order to make earlier diagnosis of rheumatoid arthritis. A total of 164 patients were included in this study. Physical examination and ultrasound examination were used to evaluate 30 joints of the wrist and hand. According to the clinical symptoms, the patients were divided into subclinical synovitis (SS) group and clinical synovitis (CS) group. The wrist and hand joints of patients with rheumatoid arthritis between the two groups were evaluated by semi-quantitative grading of musculoskeletal ultrasound, including synovitis, Power Doppler signal, joint effusion and bone erosion. We found that the total score of semi-quantitative ultrasound, synovitis score and Power Doppler signal score in the SS group were lower than those in the CS group (P<0.05). There was no significant difference in joint effusion score and bone erosion score (P>0.05). In the analysis of laboratory examination, the value of anti-RA33 antibody and ESR of SS group were decreased than that of CS group, with statistically significant difference (P=0.004), while that of RF, AKA and CCP had no significant difference between the two groups (P>0.05). In this study, the author also compared the tenosynovitis between the two groups. There was statistically significant difference (P=0.033). In conclusions, semi-quantitative grading of musculoskeletal ultrasound has certain diagnostic value for the diagnosis of subclinical synovitis in wrist and hand lesion.
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The morbidity and mortality of malaria are still high. Programmed cell death-1(PD-1) is an important co-inhibitory factor and CD8 T cells with PD-1 were reported to be exhausted cells. It remains unknown what the role of CD4 T cells expressing PD-1 is and what the upstream regulating molecules of PD-1 in CD4 T cells are. The C57BL/6 mice were injected with Plasmodium yoelii (P. yoelii) in this study. Expressions of PD-1, activation markers, and cytokines were tested. The differentially expressed genes between PD-1+/- CD4 T cells were detected by microarray sequencing. Western blot, chromatin immunoprecipitation (ChIP), siRNA, hypoxia inducible factor-1α (HIF-1α) inducer and inhibitor were used to explore PD-1's upstream molecules, respectively. The proportions of PD-1+ CD4 T cells increased post P. yoelii infection. PD-1+ CD4 T cells expressed more activated surface markers and could produce more cytokines. Nuclear factor of activated T cells 1 (NFATc1) was found to be a key transcription factor to induce PD-1 expression after infection. Both the inducer and the inhibitor of HIF-1α could change the expressions of NFATc1 and PD-1 in vivo and in vitro, respectively. Taken together, P. yoelii infection induced NFATc1 expression by HIF-1α. The highly expressed NFATc1 entered the nucleus and initiated PD-1 expression. PD-1+ CD4 T cells appeared to be more activated and could secrete more cytokines to regulate the host's immune responses against malaria.
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Linfócitos T CD4-Positivos , Subunidade alfa do Fator 1 Induzível por Hipóxia , Malária , Fatores de Transcrição NFATC , Plasmodium yoelii , Receptor de Morte Celular Programada 1 , Animais , Linfócitos T CD4-Positivos/imunologia , Citocinas/imunologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/imunologia , Malária/genética , Malária/imunologia , Malária/parasitologia , Camundongos , Camundongos Endogâmicos C57BL , Fatores de Transcrição NFATC/genética , Fatores de Transcrição NFATC/imunologia , Receptor de Morte Celular Programada 1/genética , Receptor de Morte Celular Programada 1/imunologia , Transdução de SinaisRESUMO
OBJECTIVE: To investigate the relationships between constitutional types of traditional Chinese medicine (TCM) and motion sickness. METHODS: A survey of TCM constitutions in ocean sailors participating in a voyage was performed by using the TCM Constitution Questionnaire developed by Beijing University of Traditional Chinese Medicine, while the survey of motion sickness was operated by Graybiel's diagnostic criteria. The incidences of motion sickness among sailors with different types of constitutions were compared. RESULTS: Prior to the voyage, 50.3% of sailors exhibited a gentleness constitution, 14.5% were of dampness-heat constitution, 10.3% were of qi-stagnation constitution, whereas the percentages of qi-deficiency, yang-deficiency, yin-deficiency, blood-stasis and special diathesis constitutions were 6.2%, 7.6%, 6.2%, 4.1% and 0.7%, respectively. None exhibited a phlegm-dampness constitution. By the end of the 176-day voyage, the percentages of gentleness, dampness-heat, qi-depression, qi-deficiency, yang-deficiency, yin-deficiency, blood-stasis, special diathesis and phlegm-dampness constitutions were 33.8%, 13.8%, 13.1%, 11.0%, 6.9%, 9.7%, 4.1%, 0.7% and 6.9%, respectively. The incidence of motion sickness was 69.7% (101 sailors) during this voyage. The incidences of motion sickness among sailors with different types of constitutions before the voyage showed significant difference (P<0.001). The incidence of motion sickness was higher in the sailors with dampness-heat constitution than in those with gentleness constitution. CONCLUSION: Types of Chinese medical constitution can be related to susceptibility to motion sickness. Furthermore, ocean voyage may have an effect or influence on the type of Chinese medical constitution of sailors involved.
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Constituição Corporal , Medicina Tradicional Chinesa , Enjoo devido ao Movimento/etiologia , Adulto , Humanos , Masculino , Militares , Enjoo devido ao Movimento/diagnóstico , Adulto JovemRESUMO
OBJECTIVE: To investigate the antimotion sickness effects of ginsenosides combined with dexamethasone in rats. METHODS: Fifty SD rats were randomly divided into 5 groups: normal saline, scopolamine-treated, ginsenosides-treated, dexamethasone-treated and ginsenosides plus dexamethasone-treated groups. There were 10 rats in each group. The rats in each group were fed with corresponding ingredients respectively, and then the rats were exposed to abnormal acceleration for one hour. The motion sickness index, the level of kaolin consumption and the course and time of spontaneous activity were observed. RESULTS: The motion sickness index and the level of kaolin consumption of acceleration-exposed rats in ginsenosides plus dexamethasone-treated group were significantly lower than those in normal saline group. And the course and time of spontaneous activity of acceleration-exposed rats in ginsenosides plus dexamethasone-treated group were significantly higher than those in normal saline group. The level of body weight increment of acceleration-exposed rats in ginsenosides plus dexamethasone-treated group was significantly higher than that in dexamethasone-treated group. CONCLUSION: Ginsenosides combined with dexamethasone can significantly increase tolerance to acceleration of rats, and the drug combination can decrease side effects of methylprednisolone, such as body weight loss.
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Dexametasona/farmacologia , Ginsenosídeos/farmacologia , Enjoo devido ao Movimento/tratamento farmacológico , Animais , Dexametasona/uso terapêutico , Quimioterapia Combinada , Ginsenosídeos/uso terapêutico , Masculino , Fitoterapia , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND: Cranioplasty is a common procedure in neurosurgery. It is usually performed following decompressive craniectomy (DC). However, complications may occur after the operation, such as massive brain swelling. Up to now, far too little attention has been given to this severe complication. We report one case of fatal cerebral swelling after cranioplasty and analyze the possible mechanism of this complication. CASE DESCRIPTION: The patient was a 40-year-old man who had a severe right basal ganglia cerebral hemorrhage and underwent DC â¼ 2 months before. One day before scheduled cranioplasty, a lumbar cerebrospinal fluid drainage was placed. The cranioplasty itself was uneventful. However, he gradually fell into a coma, and his right pupil was moderately dilated 20 hours after the surgery. A brain computed tomography (CT) scan indicated massive right cerebral edema with compressed right midbrain. The patient did not regain consciousness, and he remained quadriplegic. CONCLUSION: It is necessary to increase awareness of complications of cranioplasty in high-risk patients. The lessons learned from this case include avoiding excessive drainage of cerebrospinal fluid. Patients with low-density lesions in the brain need to be treated with caution. Once the CT scan shows massive cerebral swelling, the patient has a poor prognosis.
Assuntos
Hemorragia dos Gânglios da Base/cirurgia , Edema Encefálico/etiologia , Craniectomia Descompressiva/efeitos adversos , Procedimentos de Cirurgia Plástica/efeitos adversos , Adulto , Hemorragia dos Gânglios da Base/diagnóstico por imagem , Edema Encefálico/diagnóstico por imagem , Drenagem , Humanos , Masculino , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/etiologia , Tomografia Computadorizada por Raios XRESUMO
The line emission peak of Eu2+ ion in crystal KMgF3 is at 360 nm. The probability of stimulated emission on 4f7 (6 P7/2 )-->4f7 (8 S7/2 ) transition was predicted with a four-level decay model of Eu2+ 6P7/2 excited states proposed by the authors. Optic gain and net gain coefficient (g=11. 4+/-3. 2)cm(-1) of 360 nm emission in crystal KMgF3 : Eu2+ were measured by ASE method, and the predication was proved by experiment. The net gain coefficient can be increased by annealing or doping crystal KMgF3 : Eu2+ with Gd3+ or Ce+.
RESUMO
A new oil-in-water microemulsion containing 0.375% meloxicam was developed in order to improve the skin permeability of meloxicam. Among various surfactants and cosurfactants investigated in the microemulsion system, polyoxyethylene sorbitan trioleate (Tween 85) showed excellent solubility and ethanol expressed skin permeation enhancing effect for meloxicam. The microemulsion existence ranges were defined through the construction of the pseudo-ternary phase diagram. The effect of the content of isopropyl myristate (IPM) and the effect of the mass ratio of the surfactant/cosurfactant (Km) on skin permeation of meloxicam were evaluated with excised rat skins. The optimum formulation with the highest skin permeation rate (5.40 microg/cm2/h) consisted of 0.375% meloxicam, 5% IPM, 50% Tween 85/ethanol (1:1) and water.