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Structural damage detection is of significance for maintaining the structural health. Currently, data-driven deep learning approaches have emerged as a highly promising research field. However, little progress has been made in studying the relationship between the global and local information of structural response data. In this paper, we have presented an innovative Convolutional Enhancement and Graph Features Fusion in Transformer (CGsformer) network for structural damage detection. The proposed CGsformer network introduces an innovative approach for hierarchical learning from global to local information to extract acceleration response signal features for structural damage representation. The key advantage of this network is the integration of a graph convolutional network in the learning process, which enables the construction of a graph structure for global features. By incorporating node learning, the graph convolutional network filters out noise in the global features, thereby facilitating the extraction to more effective local features. In the verification based on the experimental data of four-story steel frame model experiment data and IASC-ASCE benchmark structure simulated data, the CGsformer network achieved damage identification accuracies of 92.44% and 96.71%, respectively. It surpassed the existing traditional damage detection methods based on deep learning. Notably, the model demonstrates good robustness under noisy conditions.
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Background: Aim to investigate bile acid profile changes and the Farnesoid X receptor (FXR) status after ileotransposition (IT), and reveal its possible hypoglycemic mechanism. Methods: Twenty male diabetic rats were randomly assigned into the IT group and the sham IT (SH) group. Bile acid profiles were measured using an ultra-performance liquid chromatography-tandem mass spectrometry. Glucose metabolism was monitored after oral administration of FXR inhibitor and agonist. And the expression of key FXR target genes were measured. Results: The levels of ß-muricholic acid (P = 0.047), tauro-α-muricholic acid and tauro-ß-muricholic acid (P < 0.001) in plasma in the IT group were higher than those in the SH group, and the levels of taurocholic acid (P = 0.049) and turoursodeoxycholic acid (P = 0.030) were lower than those in the SH group. After inhibition of intestinal FXR, the glucose metabolism in the SH group was improved. When FXR agonist was given, the blood glucose level was increased in both groups. After sacrifice, the levels of glycoursodeoxycholic acid, tauro-α-muricholic acid and tauro-ß-muricholic acid in liver and ileum tissues were higher than those in the SH group (P < 0.05), the level of α- muricholic acid (P < 0.001) in liver tissues were lower than that in the SH group. Moreover, the expression of CYP7A1 mRNA (P < 0.001) and FGF15 mRNA (P = 0.001) in the IT group was significantly higher, and the expression of PEPCK mRNA (P = 0.004), SREPB1c mRNA (P = 0.005) and SRB1 mRNA (P = 0.001) were significantly lower than that in the SH group. Conclusions: We demonstrate a remarkable heterogeneity of BA profiles after IT, FXR activation might has a detrimental effect on glucose metabolism.
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Diabetes Mellitus Experimental , Hipoglicemiantes , Ratos , Masculino , Animais , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/metabolismo , Íleo , Ácidos e Sais Biliares , Fígado , Glucose/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
BACKGROUND: Clinically useful predictors for fatal toxoplasmosis are lacking. We investigated the value of serological assays for antibodies to whole Toxoplasma antigens and to peptide antigens of the Toxoplasma cyst matrix antigen 1 (MAG1), for predicting incident toxoplasmic encephalitis (TE) in people living with human immunodeficiency virus (HIV; PLWH). METHODS: We performed a nested case control study, conducted within the Multicenter AIDS Cohort Study (MACS), using serum samples obtained 2 years prior to diagnosis of TE from 28 cases, and 37 HIV disease-matched Toxoplasma seropositive controls at matched time-points. Sera were tested for Toxoplasma antibodies using a commercial assay and for antibodies to MAG1_4.2 and MAG1_5.2 peptides in enzyme-linked immunosorbent assay (ELISA). RESULTS: Two years prior to clinical diagnosis, 68% of TE cases were MAG1_4.2 seropositive compared with 16% of controls (odds ratio [OR] 25.0, 95% confidence interval [CI] 3.14-199.18). Corresponding results for MAG1_5.2 seropositivity were 36% and 14% (OR 3.6, 95% CI .95-13.42). Higher levels of antibody to MAG1_4.2 (OR 18.5 per doubling of the optical density [OD] value, 95% CI 1.41-242) and to Toxoplasma (OR 2.91 for each OD unit increase, 95% CI 1.48-5.72) were also associated with the risk of TE. When seropositivity was defined as the presence of MAG1 antibody or relatively high levels of Toxoplasma antibody, the sensitivity was 89% and specificity was 68% for subsequent TE. CONCLUSIONS: Antibodies to MAG1 showed predictive value on the occurrence of TE in PLWH, and the predictive performance was further improved by adding the levels of Toxoplasma antibody. These measures could be clinically useful for predicting subsequent diseases in multiple at-risk populations.
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Encefalite , Infecções por HIV , Toxoplasma , Toxoplasmose Cerebral , Anticorpos Antiprotozoários , Estudos de Casos e Controles , Estudos de Coortes , Ensaio de Imunoadsorção Enzimática , HIV , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Humanos , Imunoglobulina G , Toxoplasmose Cerebral/epidemiologiaRESUMO
Mania is a serious neuropsychiatric condition associated with significant morbidity and mortality. Previous studies have suggested that environmental exposures can contribute to mania pathogenesis. We measured dietary exposures in a cohort of individuals with mania and other psychiatric disorders as well as in control individuals without a psychiatric disorder. We found that a history of eating nitrated dry cured meat but not other meat or fish products was strongly and independently associated with current mania (adjusted odds ratio 3.49, 95% confidence interval (CI) 2.24-5.45, p < 8.97 × 10-8). Lower odds of association were found between eating nitrated dry cured meat and other psychiatric disorders. We further found that the feeding of meat preparations with added nitrate to rats resulted in hyperactivity reminiscent of human mania, alterations in brain pathways that have been implicated in human bipolar disorder, and changes in intestinal microbiota. These findings may lead to new methods for preventing mania and for developing novel therapeutic interventions.
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Mania/fisiopatologia , Produtos da Carne/efeitos adversos , Nitratos/efeitos adversos , Adulto , Animais , Transtorno Bipolar/etiologia , Transtorno Bipolar/metabolismo , Transtorno Bipolar/fisiopatologia , Encéfalo/fisiopatologia , Feminino , Humanos , Hipercinese/metabolismo , Masculino , Mania/etiologia , Mania/metabolismo , Produtos da Carne/análise , Ratos , Ratos Sprague-DawleyRESUMO
Objective To investigate the incidence of surgical site infection(SSI)following conversion from laparoscopic to open cholecystectomy and to analyze the related risk factors. Methods The clinical data of 179 patients who had experienced conversion from laparoscopic to open cholecystectomy in Peking Union Medical College Hospital from January 2014 to August 2019 were analyzed retrospectively.Univariate and multivariate logistic regression analyses were performed to evaluate the associations between clinical variables and SSI. Results The incidence of SSI was 19.0%(34/179)after conversion from laparoscopic to open cholecystectomy.The multivariable analysis demonstrated that preoperative endoscopic retrograde cholangiopancreatography(ERCP)(OR=4.208,95% CI:1.590-11.135,P=0.004)was the only independent risk factor of SSI. Conclusions The incidence of SSI after conversion from laparoscopic to open cholecystectomy increased remarkably,especially in those who had preoperative ERCP.Preventive interventions should be taken to reduce the incidence of SSI.
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Laparoscopia , Infecção da Ferida Cirúrgica , Colecistectomia , Humanos , Estudos Retrospectivos , Fatores de Risco , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/etiologiaRESUMO
BACKGROUND: Cystic lymphangioma is a rare, benign developmental disease, mostly affecting the cervical and axial regions. The clinical features of abdominal cystic lymphangioma (ACL) are reported among pediatric patients but are less well known in adults. The purpose of this study was to demonstrate the clinical characteristics of ACL in Chinese adults and describe our experience in treating this disease. METHODS: We conducted a single-center, non-interventional, retrospective study of 12 adult patients with ACL admitted to Peking Union Medical College Hospital in Beijing, China from November 1984 through August 2017. The demographic, clinical, laboratory, imaging, histopathologic, and therapeutic data were collected. RESULTS: Detailed information on seven males and five females was available. The mean age at diagnosis was 39.1 (SD 17.3) years. The mean duration of follow-up was 6.9 years. Six (50%) patients were asymptomatic, and abdominal pain was the leading symptom for three (25%) patients. The cysts were evaluated by ultrasound (n = 8, 67%), CT (n = 10, 83%), and MRI (n = 4, 33%). Therapeutic modalities include laparotomy (n = 6, 50%), laparoscopy (n = 4, 33%), and aspiration (n = 2, 17%), with variable outcomes. The mean postsurgical hospital stay was 6.8 days. Complete excision was accomplished in eight patients, and one recurrence was observed during follow-up. Of patients who underwent partial resection, one experienced disease relapse. CONCLUSIONS: This is the first report on an Asian cohort of adult patients with ACL. Typical imaging features could lead to timely diagnosis and treatment of ACL. Radical resection is recommended with a longer period of follow-up. The analysis of this cohort deepens our understanding of adult ACL.
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Linfangioma Cístico , Adulto , Criança , China , Feminino , Humanos , Linfangioma Cístico/diagnóstico por imagem , Linfangioma Cístico/cirurgia , Masculino , Recidiva Local de Neoplasia , Neoplasias Retroperitoneais , Estudos RetrospectivosRESUMO
BACKGROUND: We herein report a rare case of an ectopic bronchogenic cyst of the gastric cardia. The initial diagnosis was a gastrointestinal stromal tumor (GIST); however, postoperative pathologic examination confirmed that it was a bronchogenic cyst. CASE PRESENTATION: A 62-year-old woman visited our hospital for abdominal pain. The diagnosis prior to surgery was a GIST. Computed tomography imaging showed that the mass was located in the gastric cardia on the side of the lesser curvature. During the surgical exploration, it was noted that the tactility of the mass was not consistent with a GIST. Thus, we decided to perform local resection of the mass and part of the gastric wall without wedge resection. The pathological examination revealed a bronchogenic cyst. CONCLUSIONS: This case suggests that a bronchogenic cyst should be considered as a differential diagnosis of a GIST. It is also a unusual but necessary situation should be considered when explaining the etiology of a bronchogenic cyst.
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Cisto Broncogênico/diagnóstico , Tumores do Estroma Gastrointestinal/diagnóstico , Neoplasias Gástricas/diagnóstico , Dor Abdominal/etiologia , Cárdia/patologia , Diagnóstico Diferencial , Feminino , Tumores do Estroma Gastrointestinal/patologia , Humanos , Pessoa de Meia-Idade , Neoplasias Gástricas/cirurgia , Tomografia Computadorizada por Raios XRESUMO
Toxoplasma gondii, a common neurotropic parasite, is increasingly being linked to neuropsychiatric disorders, including schizophrenia, Alzheimer's disease, and Parkinson's disease. However, the pathogenic mechanisms underlying these associations are not clear. Toxoplasma can reside in the brain for extensive periods in the form of tissue cysts, and this process requires a continuous immune response to prevent the parasite's reactivation. Because neuroinflammation may promote the onset and progression of neurodegenerative diseases, we investigated neurodegeneration-associated pathological changes in a mouse model of chronic Toxoplasma infection. Under conditions of high-grade chronic infection, we documented the presence of neurodegeneration in specific regions of the prefrontal cortex, namely, the anterior cingulate cortex (ACC) and somatomotor cortex (SC). Neurodegeneration occurred in both glutamatergic and GABAergic neurons. Neurons that showed signs of degeneration expressed high levels of CX3CL1, were marked by profoundly upregulated complement proteins (e.g., C1q and C3), and were surrounded by activated microglia. Our findings suggest that chronic Toxoplasma infection leads to cortical neurodegeneration and results in CX3CL1, complement, and microglial interactions, which are known to mediate the phagocytic clearance of degenerating neurons. Our study provides a mechanistic explanation for the link between Toxoplasma infection and psychiatric disorders.
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Encéfalo/parasitologia , Ativação do Complemento/fisiologia , Microglia/fisiologia , Doenças Neurodegenerativas/etiologia , Toxoplasmose/complicações , Animais , Quimiocina CX3CL1/fisiologia , Doença Crônica , Modelos Animais de Doenças , Feminino , Camundongos , Ácido gama-Aminobutírico/fisiologiaRESUMO
Anti-NMDA receptor (NMDAR) autoantibodies have been postulated to play a role in the pathogenesis of NMDAR hypofunction, which contributes to the etiology of psychotic symptoms. Toxoplasma gondii is a pathogen implicated in psychiatric disorders and associated with elevation of NMDAR autoantibodies. However, it remains unclear whether parasite infection is the cause of NMDAR autoantibodies. By using mouse models, we found that NMDAR autoantibody generation had a strong temporal association with tissue cyst formation, as determined by MAG1 antibody seroreactivity (r = 0.96; P < 0.0001), which is a serologic marker for the cyst burden. The presence of MAG1 antibody response, but not T. gondii IgG response, was required for NMDAR autoantibody production. The pathogenic relevance of NMDAR autoantibodies to behavioral abnormalities (blunted response to amphetamine-triggered activity and decreased locomotor activity and exploration) and reduced expression of synaptic proteins (the GLUN2B subtype of NMDAR and PSD-95) has been demonstrated in infected mice. Our study suggests that NMDAR autoantibodies are specifically induced by persistent T. gondii infection and are most likely triggered by tissue cysts. NMDAR autoantibody seroreactivity may be a novel pathological hallmark of chronic toxoplasmosis, which raises questions about NMDAR hypofunction and neurodegeneration in the infected brain.
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Autoanticorpos/imunologia , Encéfalo/patologia , Receptores de N-Metil-D-Aspartato/imunologia , Toxoplasma/fisiologia , Toxoplasmose/parasitologia , Toxoplasmose/psicologia , Animais , Comportamento Animal , Encéfalo/imunologia , Encéfalo/parasitologia , Encéfalo/fisiopatologia , Doença Crônica , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Atividade Motora , Neuropatologia , Toxoplasmose/imunologia , Toxoplasmose/patologiaRESUMO
Exposure to the neurotropic parasite, Toxoplasma gondii, causes significant brain and behavioral anomalies in humans and other mammals. Understanding the cellular mechanisms of T. gondii-generated brain pathologies would aid the advancement of novel strategies to reduce disease. Complement factor C1q is part of a classic immune pathway that functions peripherally to tag and remove infectious agents and cellular debris from circulation. In the developing and adult brain, C1q modifies neuronal architecture through synapse marking and pruning. T. gondii exposure and complement activation have both been implicated in the development of complex brain disorders such as schizophrenia. Thus, it seems logical that mechanistically, the physiological pathways associated with these two factors are connected. We employed a rodent model of chronic infection to investigate the extent to which cyst presence in the brain triggers activation of cerebral C1q. Compared to uninfected mice, cortical C1q was highly expressed at both the RNA and protein levels in infected animals bearing a high cyst burden. In these mice, C1q protein localized to cytoplasm, adjacent to GFAP-labeled astrocytes, near degenerating cysts, and in punctate patterns along processes. In summary, our results demonstrated an upregulation of cerebral C1q in response to latent T. gondii infection. Our data preliminarily suggest that this complement activity may aid in the clearance of this parasite from the CNS and in so doing, have consequences for the connectivity of neighboring cells and synapses.
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Córtex Cerebral/imunologia , Córtex Cerebral/parasitologia , Complemento C1q/metabolismo , Toxoplasmose/imunologia , Animais , Doença Crônica , Cistos/imunologia , Feminino , CamundongosRESUMO
OBJECTIVE: To summarize experience in the diagnosis and treatment of pancreatic cystic neoplasms. METHODS: This is a retrospective study of 207 patients who were diagnosed with pancreatic cystic tumors at Peking Union Medical College Hospital between Jan 2009 and Mar 2014. Clinical data, such as clinical manifestations, radiological and pathological images and surgical recordings, were collected. RESULTS: Of the 207 included patients, females accounted for 76.81%, and the mean patient age was 52.04 years. Malignancy was more common in older patients who presented with marasmus and jaundice. Other risk factors included solid components in the tumor, a large tumor size, and elevated levels of tumor markers. Surgical treatment was required when a malignant tumor was suspected. The operation approach was selected based on the location, size and characteristics of the tumor. The position of the tumor relative to the pancreatic duct also played a significant role. CONCLUSIONS: No specific symptoms were observed for the patients with pancreatic cystic tumors. Imaging played an important role in making a differential diagnosis. Furthermore, surgical treatment should be proposed for patients with significant symptoms and potentially malignant tumors. The tumor resection rate is high, suggestive of good prognosis.
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MicroRNA-132 (miR-132) has been demonstrated to affect multiple neuronal functions and its dysregulation is linked to several neurological disorders. We previously showed that acute Toxoplasma gondii infection induces miR-132 expression both in vitro and in vivo. To investigate the impact of chronic infection on miR-132, we infected mice with T. gondii PRU strain and performed assessment 5 months later in six brain regions (cortex, hypothalamus, striatum, cerebellum, olfactory bulb and hippocampus) by qPCR. We found that while acute infection of T. gondii increases the expression of miR-132, chronic infection has the opposite effect. The effect varied amongst different regions of the brain and presented in a sex-dependent manner, with females exhibiting more susceptibility than males. MiR-132 and brain-derived neurotrophic factor (BDNF, an inducer of miR-132) were not co-varies in the brain areas of infected mice. T. gondii DNA/RNA was found in all tested brain regions and a selective tropism towards the hippocampus, based on bradyzoite density, was observed in both males and females. However, the expressions of miR-132 or BDNF were poorly reflected by the density of T. gondii in brain areas. Our findings highlight the importance of investigating the miR-132-mediated neuronal function in mice infected with T. gondii.
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Encéfalo/parasitologia , MicroRNAs/metabolismo , Toxoplasmose Animal/metabolismo , Toxoplasmose Cerebral/metabolismo , Animais , Encéfalo/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Regulação para Baixo , Feminino , Fibroblastos/parasitologia , Regulação da Expressão Gênica , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , MicroRNAs/genética , Carga Parasitária , Reação em Cadeia da Polimerase em Tempo Real , Transcrição Reversa , Fatores Sexuais , ToxoplasmaRESUMO
Brain infection by the parasite Toxoplasma gondii is thought to impair learning and memory, although the underlying mechanisms remain largely unknown. Recent studies suggest that perineuronal nets (PNNs) and their key regulator, matrix metalloproteinase-9 (MMP-9), have essential roles in synaptic plasticity associated with learning and memory. We investigated their roles in a chronic toxoplasmosis model using female mice. In mice with a high parasite burden of chronic infection, we found that MMP-9 expression was increased in the peripheral circulation and the brain. A correlation was found between the serum levels of MMP-9 and antibodies to the Toxoplasma matrix antigen MAG1, a surrogate marker for Toxoplasma tissue cysts in the brain. MMP-9 elevation was accompanied by increased expression of its endogenous regulators, TIMP-1 and NGAL. An increase in the levels of GSK-3α/ß was observed, alongside a decrease in inhibitory GSK-3α/ß (Ser-21/Ser-9) phosphorylation. MMP-9 expression was notably associated with the loss of PNNs but increased expression of the synaptic vesicle protein synaptophysin. There was a trend toward a negative correlation between MMP-9 and aggrecan expression, a critical PNN component. Together, these results suggest that chronic Toxoplasma infection can cause an increase in MMP-9 expression, resulting in the degradation of PNNs, which provides a possible mechanism for Toxoplasma-associated deficits in learning and memory.
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BACKGROUND: Bile acids can stimulate the secretion of glucagon-like peptide-1 (GLP-1) and be mostly reabsorbed in the ileum. OBJECTIVES: We aimed to investigate whether ileum excision could reverse the glucose improvement after biliopancreatic diversion with duodenal switch (BPD/DS). SETTING: Peking Union Medical College Hospital. METHODS: Thirty diabetic rats were randomly divided into the BPD/DS group, BPD/DS plus ileectomy (BDI) group, and control group. The fasting blood glucose, bile acids, and glucagon-like peptide-1(GLP-1) levels in plasma samples were analyzed. RESULTS: In postoperative week 20, the fasting blood glucose level in the BDI group was significantly higher than that in the BPD/DS group (11.5 ± 1.4 mmol/L versus 7.6 ± 1.0 mmol/L, P < .001), and the AUCOGTT value was also significantly higher than that in the BPD/DS group (2186.1 ± 237.2 mmol/L·min versus 1551.2 ± 136.9 mmol/L·min, P < .001). The plasma level of bile acids in the BDI group was lower than that in the BPD/DS group (P = .012) and was not significantly different from that in the control group (P = .629). The plasma level of GLP-1 in the BDI group was lower than that in the BPD/DS group (P = .009) and was not significantly different from that in the control group (P = .530). Moreover, the intestinal TGR5 expression in the BDI group was significantly lower than that in the BPD/DS group (P < .001). CONCLUSIONS: The results show that excision of the ileum can partially reverse the improvement in glucose metabolism after BPD/DS.
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Aim: This article aimed to find appropriate pancreatic cancer (PC) patients to treat with Gemcitabine with better survival outcomes by detecting hENT1 levels. Methods: We collected surgical pathological tissues from PC patients who received radical surgery in our hospital from September 2004 to December 2014. A total of 375 PC tissues and paired adjacent nontumor tissues were employed for the construction of 4 tissue microarrays (TMAs). The quality of the 4 TMAs was examined by HE staining. We performed immunohistochemistry analysis to evaluate hENT1 expression in the TMAs. Moreover, we detected hENT1 expression level and proved the role of hENT1 in cell proliferation, drug resistance, migration and invasion in vivo and vitro. Results: The results indicated that low hENT1 expression indicated a significantly poor outcome in PC patients, including shortened DFS (21.6±2.8 months versus 36.9±4.0 months, p<0.001) and OS (33.6±3.9 versus 39.6±3.9, p=0.004). Meanwhile, patients in stage I/II of TNM stage had a longer OS (40.2±3.4 versus 15.4±1.7, p=0.002) and DFS (31.0±3.1 versus 12.4±1.9, p=0.016) than patients in stage III/IV. Patients in M0 stage had a longer OS (39.7±3.4 versus 16.2±1.9, p=0.026) and DFS(30.7±3.0 versus 11.8±2.2, p=0.031) than patients in M1 stage, and patients with tumors not invading the capsule had a better DFS than those with tumor invasion into the capsule (30.8±3.0 versus 12.6±2.3, p=0.053). Patients with preoperative CA19-9 values ≤467 U/mL have longer DFS than that of patients who had preoperative CA19-9 values >467 U/mL (37.9±4.1 versus 22.9±4.0, p=0.04). In the subgroup analysis, a high hENT1 expression level was related to a longer OS(39.4±4.0 versus 31.5±3.9, p=0.001) and DFS(35.7±4.0 versus 20.6±2.7; p<0.0001) in the Gemcitabine subgroup. Conclusion: PC patients with high hENT1 expression have a better survival outcomes when receiving Gemcitabine. hENT1 expression can be a great prognostic indicator for PC patients to receive Gemcitabine treatment.
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Since Toxoplasma gondii can establish a persistent infection in the central nervous system in humans, we studied its effects on a host's neurotransmitter and neuropeptide systems (NNS). Using microarray technology, we have screened the expression of genes coding for NNS in human neuroepithelioma cells in response to representative strains of Toxoplasma to identify potential target genes. Transcripts that displayed expression levels distinct from uninfected controls were examined by RT-PCR and Western blot. Our results indicate the presence of disturbed NNS upon Toxoplasma infection and the extent of this disturbance varies considerably among the three strains. In cells infected by type I strain, three neurotransmitter systems (dopamine, glutamate and serotonin) and two neuropeptides (PROK2 and TAC1) displayed abnormalities relative to controls. Type III infection led to the change of a critical enzyme, TDO2, in the kynurenine pathway. No significant effects of type II infection were found in the NNS. These data may have implications for understanding the pathogenesis and heterogeneity of neurologic disturbances in toxoplasmosis.
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Células Neuroepiteliais/metabolismo , Células Neuroepiteliais/microbiologia , Neuropeptídeos/metabolismo , Neurotransmissores/metabolismo , Toxoplasma/genética , Toxoplasmose/genética , Análise de Variância , Linhagem Celular Tumoral , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Neuroblastoma/patologia , Neuropeptídeos/genética , Neurotransmissores/genética , Análise de Sequência com Séries de Oligonucleotídeos , RNA Mensageiro/metabolismo , Receptores de Neurotransmissores/genética , Receptores de Neurotransmissores/metabolismo , Toxoplasma/classificaçãoRESUMO
BACKGROUND/AIMS: Individualized chemotherapy is important in the treatment of pancreatic cancer. Therefore, markers for predicting a patient response to treatment must be identified. We studied the relationship between human equilibrative nucleoside transporter 1 (hENT1) expression in tumor cells and the Asian patient response to gemcitabine-based chemotherapy. The aim of the study was to identify markers for individualized chemotherapy in Asian patients with pancreatic cancer. METHODOLOGY: Specimens from 44 Asian patients diagnosed with pancreatic adenocarcinoma were analyzed by immunohistochemistry for hENT1 expression in tumor cells. The correlations between hENT1 expression and various clinicopathological factors, including survival status, were studied. RESULTS: The overall survival (OS) and disease-free survival (DFS) in the hENT1 high-expression group were significantly longer than those of the hENT1 low or no-expression group: OS 21.75 months (95%CI=18.45-25.04 months) vs. 12.48 months (95%CI=10.12-14.85 months); DFS 15.44 months (95%CI=11.26-19.62 months) vs. 8.24 months (95%CI=8.69-9.78 months), respectively. CONCLUSIONS: Our studies suggest that hENT1 expression is related to the patient response to gemcitabine-based chemotherapy in Asian patients with pancreatic cancer. Therefore, hENT1 may be a valuable prognostic marker for individualized chemotherapy in pancreatic cancer.
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Antimetabólitos Antineoplásicos/administração & dosagem , Desoxicitidina/análogos & derivados , Transportador Equilibrativo 1 de Nucleosídeo/análise , Neoplasias Pancreáticas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Povo Asiático , Desoxicitidina/administração & dosagem , Intervalo Livre de Doença , Transportador Equilibrativo 1 de Nucleosídeo/genética , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Pancreáticas/química , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Prognóstico , RNA Mensageiro/análise , GencitabinaRESUMO
Chronic infection with Toxoplasma gondii, a neurotropic parasite, has been linked to multiple behavioral changes in rodents and humans. The pathogenic mechanisms underlying these correlations are not known. I discuss here from animal studies the distribution of tissue cysts, the constant immune surveillance, the critical role of cyst burden, and the time-dependent consequences, which I believe are crucial to explaining the behavioral changes. In line with the brain-wide distribution of tissue cysts and chronic neuroinflammation, infected mice displayed a broad range of behavioral phenotypes. Many studies suggest that behavioral changes in mice are directly associated with tissue cyst presence or cyst burden and the host immune response. Cyst burden may not exert direct effects; however, the mechanisms causing behavioral and neuropathological changes are potentially the consequence of cyst burden over time, such as the neuroinflammation required to control the reactivation of tissue cysts. The reduction of neuroinflammation has proven that neuropathogenesis and behavioral abnormalities can be reversed, at least partially, in infected mice. Overall, Toxoplasma-induced behavioral changes are likely to be an indirect consequence of the host immune response in a parasite burden-dependent manner.
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Toxoplasma , Toxoplasmose , Humanos , Camundongos , Animais , Doenças Neuroinflamatórias , Toxoplasmose/complicações , Toxoplasma/genética , Encéfalo/patologia , Inflamação/complicações , Inflamação/patologiaRESUMO
BACKGROUND AND PURPOSE: Diagnosis of retroperitoneal schwannoma (RS), especially cystic RS, is frequently missed or delayed owing to its rarity, location, nonspecific symptoms, and similarities with other tumors on various imaging modalities. This study aimed to determine associations between clinical, radiological, and histopathologic features and outcome. MATERIALS AND METHODS: Seventy-nine patients with pathologically confirmed RS who underwent tumor resection between June 2010 and June 2020 were retrospectively reviewed and analyzed. Patients were stratified into three groups according to degree of tumoral cystic degeneration. RESULTS: Cystic degeneration was significantly associated with multiple foci (p = 0.025), calcification (p = 0.012), and hemorrhage (p = 0.000), but not size (p = 0.08), high Ki-67 (p = 0.094), malignancy (p = 0.115; prevalence of cystic degeneration in the benign and malignant groups were 53.9% vs 100%), rough margin (p = 0.162), or irregular shape (p = 0.369). Malignant RS was significantly associated with multiple lymph nodes enlargement (p = 0.034). Tumor size, margins, shape, or/and multiplicity did not significantly differ between benign and malignant tumors. No recurrence occurred in patients with benign RS (mean follow-up, 45 months). All malignant tumors recurred; mean time to recurrence was 11.4 months (mean follow-up, 33 months). CONCLUSION: Since RS is misdiagnosed mostly as malignancy and diagnosis is often delayed, a suspicion is necessary for diagnosis when atypical features are present. In RS, cystic degeneration was not associated with tumor size, Ki-67, or malignancy; however, it was significantly associated with multiple foci, calcification, and hemorrhage. Cystic degeneration and related factors are useful for the diagnosis of RS. Malignant RS should be considered when a mass involves multiple lymph nodes. Margins, morphology, and size are not associated with malignancy. Pathological tumor type, tumor location, and adjacent anatomic structures are associated with outcome.
Assuntos
Calcinose , Neurilemoma , Neoplasias Retroperitoneais , Humanos , Estudos Retrospectivos , Neoplasias Retroperitoneais/diagnóstico , Neoplasias Retroperitoneais/cirurgia , Antígeno Ki-67 , Prognóstico , Neurilemoma/diagnóstico , Neurilemoma/cirurgia , Neurilemoma/patologia , HemorragiaRESUMO
Toxoplasma gondii can infect the host brain and trigger neuroinflammation. Such neuroinflammation might persist for years if the infection is not resolved, resulting in harmful outcomes for the brain. We have previously demonstrated the efficacy of immunotherapy targeting the programmed cell death protein 1 (PD-1) pathway on clearance of Toxoplasma tissue cysts. We aimed to test whether parasite clearance would lead to the resolution of neuroinflammation in infected brains. We established chronic Toxoplasma infection in BALB/c mice using the cyst-forming Prugniaud strain. Mice then received αPD-L1 or isotype control antibodies. After completion of the therapy, mice were euthanized six weeks later. The number of brain tissue cysts, Toxoplasma-specific CD8 + T cell proliferation and IFN-γ secretion, serum cytokine and chemokine levels, and CNS inflammation were measured. In αPD-L1-treated mice, we observed reduced brain tissue cysts, increased spleen weight, elevated IFN-γ production by antigen-specific CD8 + T cells, and a general increase in multiple serum cytokines and chemokines. Importantly, αPD-L1-treated mice displayed attenuation of meningeal lymphocytes, reactive astrocytes, and C1q expression. The reduction in inflammation-related proteins is correlated with reduced parasite burden. These results suggest that promoting systemic immunity results in parasite clearance, which in turn alleviates neuroinflammation. Our study may have implications for some brain infections where neuroinflammation is a critical component.