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1.
Neurol Sci ; 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39088158

RESUMEN

OBJECTIVE: To investigate the efficacy of transcranial ultrasound stimulation (TUS) combined with Fastigial nucleus stimulation (FNS) on cerebral blood flow and limb function in patients in the acute phase of ischemic stroke. METHODS: A total of 90 patients in the acute phase of ischemic stroke were randomly divided into an FNS, TUS, and TUS + FNS group (30 patients each), and all patients also received conventional treatment. The FNS group was treated with FNS alone. The TUS group was treated with TUS alone. The TUS + FNS group was treated with both TUS and FNS. The three groups were treated once a day for 6 days a week. RESULTS: The simplified Fugl-Meyer Assessment (FMA) and Barthel index scores (BI), and the peak systolic blood flow velocity (Vs) and the mean blood flow velocity (Vm) of the anterior cerebral artery, middle cerebral artery, and posterior cerebral artery, were significantly higher in all three groups compared with before treatment (P < 0.05). The scores for the TUS group were higher than for the FNS group (P < 0.05), and the scores of the TUS + FNS group were higher than the TUS and FNS groups, respectively (P < 0.05). The total effective rate was 63.3%, 70.0%, and 90.0% in the FNS, TUS, and TUS + FNS groups, respectively, and the difference between the three groups was statistically significant (P < 0.05). CONCLUSION: The FNS and TUS treatments improved the function of and accelerated cerebral blood flow in patients with acute ischemic stroke to different degrees, and the combined use of both treatment types was overall more effective.

2.
Infect Drug Resist ; 17: 2923-2931, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39011345

RESUMEN

Purpose: Accurate differentiation between early and late latent syphilis stages is pivotal for patient management and treatment strategies. Nontreponemal IgM antibodies have shown potential in discriminating latent syphilis staging by differentiating syphilis activity. This study aimed to develop a predictive nomogram model for latent syphilis staging based on nontreponemal IgM antibodies. Patients and Methods: We explored the correlation between nontreponemal IgM antibodies and latent syphilis staging and developed a nomogram model to predict latent syphilis staging based on 352 latent syphilis patients. Model performance was assessed using AUC, calibration curve, Hosmer-Lemeshow χ2 statistics, C-index, Brier score, decision curve analysis, and clinical impact curve. Additionally, an external validation set was used to further assess the model's stability. Results: Nontreponemal IgM antibodies correlated with latent syphilis staging. The constructed model demonstrated a strong discriminative capability with an AUC of 0.743. The calibration curve displayed a strong fit, key statistics including Hosmer-Lemeshow χ² at 2.440 (P=0.486), a C-index score of 0.743, and a Brier score of 0.054, all suggesting favorable model calibration performance. Decision curve analysis and clinical impact curve highlighted the model's robust clinical applicability. The external validation set yielded an AUC of 0.776, Hosmer-Lemeshow χ² statistics of 2.440 (P=0.486), a C-index score of 0.767, and a Brier score of 0.054, further underscored the reliability of the model. Conclusion: The nontreponemal IgM antibody-based predicted model could equip clinicians with a valuable tool for the precise staging of latent syphilis and enhancing clinical decision-making.

3.
Int Immunopharmacol ; 126: 111204, 2024 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-38016343

RESUMEN

Glycolysis is a key pathway in cellular glucose metabolism for energy supply and regulates immune cell activation. Whether glycolysis is involved in the activation of NOD-like receptor family protein 3 (NLRP3) inflammasomes during Treponema pallidum (T. pallidum) infection is unclear. In this study, the effect of T. pallidum membrane protein Tp47 on NLRP3 inflammasome activation in rabbit peritoneal macrophages was analysed and the role of glycolysis in NLRP3 inflammasome activation was explored. The results showed that Tp47 promoted NLRP3, caspase-1, and IL-1ß mRNA expression in macrophages, enhanced glycolysis and glycolytic capacity of macrophage, and promoted the production of macrophage glycolytic metabolites citrate, phosphoenolpyruvate, and lactate. The M2 pyruvate kinase (PKM2) inhibitor shikonin down-regulated the Tp47-promoted NLRP3, caspase-1, and IL-1ß mRNA expression in macrophages, and suppressed the Tp47-enhanced glycolysis and glycolytic capacity. Similarly, si-PKM2 significantly inhibited Tp47-promoted NLRP3, caspase-1, and IL-1ß mRNA expression and the Tp47-enhanced glycolysis and glycolytic capacity in macrophages. In conclusion, Tp47 activated NLRP3 inflammasomes via PKM2-dependent glycolysis and provided a new perspective on the effect of T. pallidum infection on host macrophages, which would contribute to the understanding of the infection mechanism and host immune mechanism of T. pallidum.


Asunto(s)
Inflamasomas , Treponema pallidum , Animales , Conejos , Inflamasomas/metabolismo , Treponema pallidum/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteínas NLR/metabolismo , Macrófagos , Proteínas Recombinantes/farmacología , Caspasa 1/metabolismo , ARN Mensajero/metabolismo , Glucólisis , Interleucina-1beta/metabolismo
4.
Comb Chem High Throughput Screen ; 26(15): 2738-2748, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37066775

RESUMEN

BACKGROUND: Acute Liver Failure (ALF) is a difficult problem to solve in clinical practice. The presence of non-SMC condensin I complex subunit G (NCAPG) has previously been linked to vascular invasion of digestive system tumors, foreshadowing poor prognosis. Its role in ALF biology, however, remains unknown. This article explores the role of NCAPG as a potential biomarker candidate for the accurate diagnosis and targeted treatment of ALF. METHODS: The study included transcription data (GSE14668, GSE38941, GSE62029, GSE96851, and GSE120652) of ALF, normal tissues, and clinical samples, where NCAPG was selected as the differential gene by the "DESeq2" R package to analyze the immune cell functions and signal pathways. Furthermore, RT-qPCR and Western blot analyses were used to confirm the RNA and protein levels of NCAPG in ALF cell models, respectively. RESULTS: Bioinformatics analysis revealed that NACPG was up-regulated in ALF tissues, and the functional signaling pathway was primarily associated with immune infiltration. Based on the results of clinical samples, we suggest that NCAPG was overexpressed in ALF tissues. We also found that the expression of NCAPG increased with the degree of liver injury in vitro. Enrichment analysis suggested that NCAPG influenced ALF as a PI3K/AKT pathway activator. CONCLUSION: Our study suggests that NCAPG is a preliminary tool for the diagnosis of ALF. It can affect ALF via the PI3K/AKT pathway and is a potential therapeutic target to improve prognosis.


Asunto(s)
Biomarcadores , Proteínas de Ciclo Celular , Fallo Hepático Agudo , Humanos , Proteínas de Ciclo Celular/genética , Fallo Hepático Agudo/diagnóstico , Fallo Hepático Agudo/genética , Fallo Hepático Agudo/terapia , Neoplasias Hepáticas/patología , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt
5.
J Infect Public Health ; 15(12): 1494-1496, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36413872

RESUMEN

To evaluate the application of cycle threshold (Ct) values of coronavirus disease 2019 (COVID-19) patients in predicting epidemic dynamics and monitoring surface contamination. The Ct value of reverse transcriptase-polymerase chain reaction for SARS­CoV-2 from COVID-19 patients inbound overseas in Xiamen, China was collected from October 2020 to December 2021, and the correlation of patients' Ct values with epidemic dynamics and surface contamination was evaluated. The results showed that there was an extreme inverse correlation of positivity rate in the current calendar month (ORF1ab, r = -0.692, P = 0.004; N,r = -0.629, P = 0.012) and the following calendar month (ORF1ab,r = -0.801, P = 0.001; N,r = -0.620, P = 0.018) with the median Ct values. Ct value showed better performance for monitoring surface contamination, with the area under the curve value 0.808(95 %CI: 0.748-0.869) for ORF1ab and 0.807(95 %CI:0.746-0.868) for the N gene. The patients' ORF1ab Ct value< 29.09 or N Ct value< 28.03 were 11.25 times and 10.48 times more likely to result in surface contamination than those with ORF1ab Ct value ≥ 29.09 or N Ct value≥ 28.03 (OR:11.25,95 % CI: 5.52-22.35; OR:10.48,95 % CI:5.29-20.70). Ct values were associated with the positivity rate in the current or following calendar month and predicted the epidemic dynamics. The Ct values can be used as a predictor for monitoring surface contamination to develop public health responses to COVID-19.


Asunto(s)
COVID-19 , Epidemias , Humanos , SARS-CoV-2/genética , COVID-19/diagnóstico , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Salud Pública
6.
J Clin Lab Anal ; 36(1): e24185, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34919739

RESUMEN

BACKGROUND: Tuberculosis poses a severe threat to human health. At present, compared with the traditional diagnostic methods for tuberculosis pleural effusion, such as Löwenstein-Jensen culture, pleural biopsy, and Ziehl-Neelsen smear microscopy, Xpert MTB/RIF was regarded as an emerging technology for its efficiency. The Xpert MTB/RIF accuracy for tuberculous pleural effusion diagnosis was evaluated in this systematic study. MATERIALS AND METHODS: We searched the relevant literature published before January 2021 in PubMed, Cochrane, EMBASE, and Web of Science databases. Utilizing Review Manager 5.3 software, the quality of the included literature was evaluated based on the Quality Assessment of Diagnostic Accuracy Studies criteria. Sensitivity, specificity, and the summary receiver operating characteristic curves were plotted and analyzed with Metadisc 1.40 software. We used Stata 12.0 software to evaluate the publication bias of this study. RESULTS: Eighteen articles were identified in total. The sensitivity of Xpert MTB/RIF in the pleural effusion was 0.24, and specificity was 1.00, respectively. The area under the summary receiver operating characteristic curve was 0.9737, which indicated that the overall accuracy of the Xpert MTB/RIF was high. In addition, based on the Deeks funnel plot, no publication bias of the study was found. CONCLUSION: Xpert MTB/RIF is a rapid method with high specificity but relatively low sensitivity for detecting Mycobacterium tuberculosis in pleural effusion. Its less sensitivity made it difficult to be used clinically, but the high specificity suggests that it can be used as a specific diagnostic method for tuberculous pleural effusion.


Asunto(s)
Mycobacterium tuberculosis/aislamiento & purificación , Técnicas de Amplificación de Ácido Nucleico , Derrame Pleural/microbiología , Tuberculosis/diagnóstico , Humanos , Curva ROC , Estándares de Referencia , Sensibilidad y Especificidad
7.
Cancer Cell Int ; 21(1): 22, 2021 Jan 06.
Artículo en Inglés | MEDLINE | ID: mdl-33407468

RESUMEN

BACKGROUND: The role of methylcrotonoyl-CoA carboxylase 2 (MCCC2) in the development of tumors is well-established, and the involvement of leucine in the liver is well-known. However, the role of MCCC2 and the correlation between MCCC2 and leucine in the progression of hepatocellular carcinoma (HCC) have not yet been reported. METHODS: In this study, the Gepia database was used to evaluate the prognostic value of MCCC2 in HCC. The expression and localization of MCCC2 in HCC cells were determined by western blot and immunofluorescence assays. Flow cytometry and CCK-8 and transwell assays were carried out to explore the effect of MCCC2 on cell proliferation, migration, and invasion. In addition, mass spectrometry analysis was used to predict the potential cell function of MCCC2 in HCC. RESULTS: We found that the expression of MCCC2 increased in HCC tissues and that high expression of MCCC2 could predict poor outcomes in HCC patients. Knockdown expression of MCCC2 in HCC cells could reduce cell proliferation, migration, and invasion ability in vitro and could inhibit HCC cell proliferation in vivo. Interestingly, we found that HCC cells transfected with MCCC2-sgRNA failed to respond to leucine deprivation. Meanwhile, leucine deprivation inhibited cell proliferation, migration, and invasion in HCC cells where MCCC2 was present rather than in cells where MCCC2 was absent. In addition, knockdown of MCCC2 significantly reduced the glycolysis markers, glucose consumption, lactate secretion, and acetyl-CoA level, which is a product of leucine metabolism. Furthermore, we found that MCCC2 promotes the activation of ERK. Profiling the MCCC2 binding proteins revealed that MCCC2-associated proteins are enriched in biological processes, such as protein metabolism, energy pathway, and metabolism in HCC cells. CONCLUSIONS: Our findings revealed that MCCC2 plays a critical role in the development of HCC, and the leucine metabolism pathway might be a novel target in HCC treatment.

8.
Anal Biochem ; 611: 113950, 2020 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-32919941

RESUMEN

BACKGROUND: The aim of the study was to assess the analytical performance of the HISCL NT-proBNP assay, a newly developed chemiluminescence immunoassay, for the detection of NT-proBNP. METHODS: The within-run and total imprecision of the NT-proBNP assay were determined with HISCL cardiac marker controls. The linear ranges of the NT-proBNP assays were evaluated based on the CLSI EP6-A document using selected serum samples. Two hundred serum samples were evaluated to compare the HISCL NT-proBNP and Elecsys NT-proBNP assays. Five additional high NT-proBNP concentrations serum samples were evaluated to assess if there was high-dose hook effect in the HISCL NT-proBNP assay. RESULTS: The total and within-run imprecision values of the HISCL NT-proBNP assay were 5.85%, 0.81%, 2.56% and 0.54% and 6.07%, 0.73%, 2.61% and 0.59% at 6.1, 129.83, 3732.84and39737.33 pg/ml, respectively. The assay was verified to be linear for NT-proBNP levels ranging between 6.1 and 39737.33 pg/ml. The assay comparison showed that HISCL NT-proBNP = 0.9803 × Elecsys NT-proBNP -4.383. The sensitivity of HISCL NT-proBNP was 87.23%, and the specificity was 85.61%. The AUC of HISCL NT-proBNP (0.90 (95% CI, 0.86-0.93)) did not differ from that of Elecsys NT-proBNP(0.89 (95% CI, 0.85-0.93)) (P = 0.638). The results of five high NT-proBNP concentrations samples (44448, 54206, 55634, 55728 and 109406 pg/ml, measured with the Elecsys NT-proBNP assay) tested with HISCL NT-proBNP assay were all displayed with ">40000 pg/ml". CONCLUSIONS: The HISCL NT-proBNP chemiluminescence immunoassay showed good analytical and diagnostic performance for the detection of NT-proBNP and could be used in routine clinical practice.


Asunto(s)
Mediciones Luminiscentes , Péptido Natriurético Encefálico/análisis , Fragmentos de Péptidos/análisis , Humanos , Inmunoensayo
9.
Exp Ther Med ; 20(4): 3816-3822, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32855731

RESUMEN

Peripheral blood lymphocyte subsets have been reported to be useful as prognostic and/or diagnostic markers for patients with cancer. However, the clinical value of peripheral blood lymphocyte subsets in gastric cancer (GC) has remained elusive. In the present study, peripheral CD3+, CD4+ and CD8+ T lymphocytes, B cells (CD19+), regulatory T cells (Tregs; CD4+CD25+CD127-) and natural killer (NK) cells (CD3-CDl6+CD56+) were detected by flow cytometry in 122 patients with GC, 80 healthy donors (HDs) and 80 patients with gastric ulcer (GU). NK cells (CD56+) were detected by immunohistochemical (IHC) analysis in 20 GC and three GU tissue samples. A receiver-operating characteristic (ROC) curve was used to determine the threshold of the peripheral NK cell level and survival analysis was performed to assess its prognostic value in patients with GC. The results indicated that the peripheral NK cell proportion in patients with GC (18.77%) was significantly higher than that in the HD (12.19%) and GU (12.74%) groups. IHC analysis suggested that the NK level in GC tumor samples was correlated with that in paired serum samples. ROC curve analysis indicated that the peripheral NK cell level (15.16%) was able to effectively identify patients with GC, a diagnostic sensitivity of 75.41% and a specificity of 77.45% were determined. Multivariate logistic regression analysis revealed that the peripheral NK cell level was independently associated with the T stage and survival analysis demonstrated that high levels of peripheral NK cells were associated with poor prognosis of patients with GC. In conclusion, the peripheral NK cell level may be a diagnostic and prognostic marker for patients with GC.

10.
J Exp Clin Cancer Res ; 39(1): 123, 2020 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-32605589

RESUMEN

BACKGROUND: 3-Hydroxy butyrate dehydrogenase 2 (BDH2) is a short-chain dehydrogenase/reductase family member that plays a key role in the development and pathogenesis of human cancers. However, the role of BDH2 in gastric cancer (GC) remains largely unclear. Our study aimed to ascertain the regulatory mechanisms of BDH2 in GC, which could be used to develop new therapeutic strategies. METHODS: Western blotting, immunohistochemistry, and RT-PCR were used to investigate the expression of BDH2 in GC specimens and cell lines. Its correlation with the clinicopathological characteristics and prognosis of GC patients was analysed. Functional assays, such as CCK-8 and TUNEL assays, transmission electron microscopy, and an in vivo tumour growth assay, were performed to examine the proliferation, apoptosis, and autophagy of GC cells. Related molecular mechanisms were clarified by luciferase reporter, coimmunoprecipitation, and ubiquitination assays. RESULTS: BDH2 was markedly downregulated in GC tissues and cells, and the low expression of BDH2 was associated with poor survival of GC patients. Functionally, BDH2 overexpression significantly induced apoptosis and autophagy in vitro and in vivo. Mechanistically, BDH2 promoted Keap1 interaction with Nrf2 to increase the ubiquitination level of Nrf2. Ubiquitination/degradation of Nrf2 inhibited the activity of ARE to increase accumulation of reactive oxygen species (ROS), thereby inhibiting the phosphorylation levels of AktSer473 and mTORSer2448. CONCLUSIONS: Our study indicates that BDH2 is an important tumour suppressor in GC. BDH2 regulates intracellular ROS levels to mediate the PI3K/Akt/mTOR pathway through Keap1/Nrf2/ARE signalling, thereby inhibiting the growth of GC.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Regulación Neoplásica de la Expresión Génica , Hidroxibutirato Deshidrogenasa/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Neoplasias Gástricas/patología , Ubiquitina/metabolismo , Animales , Apoptosis , Autofagia , Biomarcadores de Tumor/genética , Movimiento Celular , Proliferación Celular , Femenino , Humanos , Hidroxibutirato Deshidrogenasa/genética , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Persona de Mediana Edad , Factor 2 Relacionado con NF-E2/genética , Pronóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Tasa de Supervivencia , Células Tumorales Cultivadas , Ubiquitinación , Ensayos Antitumor por Modelo de Xenoinjerto
11.
J Cell Mol Med ; 24(14): 7959-7967, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32510753

RESUMEN

Methyl-CpG-binding protein 2 (MeCP2) is an important epigenetic regulator for normal neuronal maturation and brain glial cell function. Additionally, MeCP2 is also involved in a variety of cancers, such as breast, prostate, lung, liver and colorectal. However, whether MeCP2 contributes to the progression of breast cancer remains unknown. In the present study, we investigated the role of MeCP2 in cell proliferation, migration and invasion in vitro. We found that knockdown of MeCP2 inhibited expression of epithelial-mesenchymal transition (EMT)-related markers in breast cancer cell lines. In conclusion, our study suggests that MeCP2 inhibits proliferation and invasion through suppression of the EMT pathway in breast cancer.


Asunto(s)
Neoplasias de la Mama/genética , Movimiento Celular/genética , Transición Epitelial-Mesenquimal/genética , Proteína 2 de Unión a Metil-CpG/genética , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Línea Celular Tumoral , Proliferación Celular , Supervivencia Celular/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Humanos , Inmunohistoquímica , Proteína 2 de Unión a Metil-CpG/metabolismo
12.
J Cell Mol Med ; 24(13): 7637-7651, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32436333

RESUMEN

The mechanism by which miR-605-3p regulates hepatocellular carcinoma (HCC) metastasis has not been clarified. In this study, we found that miR-605-3p was down-regulated in HCC and that low miR-605-3p expression was associated with tumour thrombus and tumour satellites. HCC patients with low miR-605-3p expression showed shorter overall survival and disease-free survival after surgery. Overexpression of miR-605-3p inhibited epithelial-mesenchymal transition and metastasis of HCC through NF-κB signalling by directly inhibiting expression of TRAF6, while silencing of miR-605-3p had the opposite effect. We also found that SNHG16 directly bound to miR-605-3p as a competing endogenous RNA. Mechanistically, high expression of SNHG16 promoted binding to miR-605-3p and inhibited its activity, which led to up-regulation of TRAF6 and sustained activation of the NF-κB pathway, which in turn promoted epithelial-mesenchymal transition and metastasis of HCC. TRAF6 increased SNHG16 promoter activity by activating NF-κB, thereby promoting the transcriptional expression of SNHG16 and forming a positive feedback loop that aggravated HCC malignancy. Our findings reveal a mechanism for the sustained activation of the SNHG16/miR-605-3p/TRAF6/NF-κB feedback loop in HCC and provide a potential target for a new HCC treatment strategy.


Asunto(s)
Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Retroalimentación Fisiológica , Neoplasias Hepáticas/genética , MicroARNs/metabolismo , FN-kappa B/metabolismo , ARN Largo no Codificante/metabolismo , Factor 6 Asociado a Receptor de TNF/metabolismo , Secuencia de Bases , Línea Celular Tumoral , Supervivencia Celular/genética , Supervivencia sin Enfermedad , Regulación hacia Abajo/genética , Transición Epitelial-Mesenquimal/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Hepáticas/patología , Masculino , MicroARNs/genética , Persona de Mediana Edad , Análisis Multivariante , Metástasis de la Neoplasia , Pronóstico , ARN Largo no Codificante/genética
13.
Sci Rep ; 9(1): 19691, 2019 Dec 23.
Artículo en Inglés | MEDLINE | ID: mdl-31873168

RESUMEN

Self-heating effect is a major limitation in achieving the full performance potential of high power GaN power devices. In this work, we reported a micro-trench structure fabricated on the silicon substrate of an AlGaN/GaN high electron mobility transistor (HEMT) via deep reactive ion etching, which was subsequently filled with high thermal conductive material, copper using the electroplating process. From the current-voltage characteristics, the saturation drain current was improved by approximately 17% with the copper filled micro-trench structure due to efficient heat dissipation. The IDS difference between the pulse and DC bias measurement was about 21% at high bias VDS due to the self-heating effect. In contrast, the difference was reduced to approximately 8% for the devices with the implementation of the proposed structure. Using Micro-Raman thermometry, we showed that temperature near the drain edge of the channel can be lowered by approximately ~22 °C in a HEMT operating at ~10.6 Wmm-1 after the implementation of the trench structure. An effective method for the improvement of thermal management to enhance the performance of GaN-on-Silicon HEMTs was demonstrated.

14.
Eur Neurol ; 80(1-2): 82-86, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30343296

RESUMEN

BACKGROUND: The differential diagnosis of general paresis (GP) and non-neurosyphilis (NS) dementia is not clearly defined. The present study examined the differences in clinical and laboratory features of GP and non-NS dementia. MATERIALS AND METHODS: We retrospectively examined clinical and laboratory features of 85 GP patients and 196 non-NS dementia patients. Data were collected from Zhongshan Hospital between June 2005 and June 2014. RESULTS: The GP group had a higher percentage of males (83.53%, 71/85) and younger median age ([52 [interquartile range 47.0-61.0] vs. 76 [68.3-82.0] years) than the non-NS dementia group. GP have higher Mini-Mental State Examination (MMSE; Z = -5.809; p = 0.000) than non-NS dementia. Distribution of CDR scores were significantly higher in the non-NS group than GP group (χ2 = 29.153; p = 0.000). The laboratory findings showed significantly different total cholesterol (CH), low-density lipoprotein CH and homocysteine levels between the 2 groups. Serologic testing for syphilis revealed that the GP group had higher seropositive rapid plasma reagin (RPR) and Treponema pallidum particle agglutination (TPPA) rates than the non-NS dementia group (96.47% [82/85] vs. 0.51% [1/196], Z = -2.663, p = 0.008; 100% [85/85] vs. 1.02% [2/196], Z = -2.663, p = 0.008). Interestingly, cerebrospinal fluid (CSF) biochemical indices, including pleocytosis rates, increased protein levels, and positive RPR and TPPA rates in the GP group were higher than that in the non-NS dementia group. CONCLUSIONS: Based on these preliminary data, patients with clinically evident symptoms of dementia, especially middle-aged males, should undergo blood tests for syphilis. All patients with positive serology results should undergo CSF examinations to diagnose GP dementia before further pharmaceutical and behavioral interventions.


Asunto(s)
Demencia/diagnóstico , Neurosífilis/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Demencia/sangre , Demencia/líquido cefalorraquídeo , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Neurosífilis/sangre , Neurosífilis/líquido cefalorraquídeo , Estudios Retrospectivos , Pruebas Serológicas , Treponema pallidum
15.
BMC Immunol ; 19(1): 28, 2018 09 14.
Artículo en Inglés | MEDLINE | ID: mdl-30217146

RESUMEN

BACKGROUND: The involvement of inflammasome activation and macrophage polarization during the process of syphilis infection remains unknown. In this study, A series of experiments were performed using human macrophages to research the role of NLRP3 inflammasome regulation in interleukin (IL)-1ß production and its influence on macrophage polarization triggered by T. pallidum. RESULTS: The results showed that in M0 macrophages treated with T. pallidum, the M1-associated markers inducible nitric oxide synthase (iNOS), IL-1ß and TNF-α were upregulated, and the M2-associated markers CD206 and IL-10 were downregulated. In addition, we observed NLRP3 inflammasome activation and IL-1ß secretion in T. pallidum-treated macrophages, and the observed production of IL-1ß occurred in a dose- and time-dependent manner. Moreover, the secretion of IL-1ß by macrophages after T. pallidum treatment was notably reduced by anti-NLRP3 siRNA and caspase-1 inhibitor treatment. NAC, KCl, and CA074-ME treatment also suppressed IL-1ß release from T. pallidum-treated macrophages. CONCLUSIONS: These findings showed that T. pallidum induces M0 macrophages to undergo M1 macrophage polarization and elevate IL-1ß secretion through NLRP3. Moreover, the process of NLRP3 inflammasome activation and IL-1ß production in macrophages in response to T. pallidum infection involves K+ efflux, mitochondrial ROS production and cathepsin release. This study provides a new insight into the innate immune response to T. pallidum infection.


Asunto(s)
Polaridad Celular/inmunología , Inflamasomas/inmunología , Interleucina-1beta/biosíntesis , Activación de Macrófagos , Macrófagos/inmunología , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Sífilis/inmunología , Treponema pallidum/inmunología , Catepsinas/metabolismo , Línea Celular Tumoral , Humanos , Inmunidad Innata , Especies Reactivas de Oxígeno/metabolismo , Células THP-1
16.
BMC Infect Dis ; 18(1): 101, 2018 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-29490620

RESUMEN

BACKGROUND: The inflammasome responses in Treponema pallidum infection have been poorly understood to date. This study aimed to investigate the expression of the nucleotide-binding leucine-rich receptor protein 3 (NLRP3) inflammasome in the development of tissue inflammation in rabbits infected with T. pallidum. METHODS: Forty-five rabbits were randomly assigned to a blank group or an infection group, and the latter was divided into no benzathine penicillin G (BPG) and BPG treatment subgroups. Rabbits in the infection group were injected intradermally with 0.1 mL of a 107/mL T. pallidum suspension at 10 marked sites along the back, and the blank group was treated with normal saline. The BPG treatment subgroup received 200,000 U of BPG administered intramuscularly twice, at 14 d and 21 d post-infection. The development of lesions was observed, and biopsies of the injection site and various organs, including the kidney, liver, spleen, lung, and testis, were obtained for NLRP3, caspase-1, and interleukin-1ß (IL-1ß) mRNA analysis during infection. Blood was also collected for the determination of IL-1ß concentration. RESULTS: Rabbits infected with T. pallidum (both the BPG treatment and no BPG treatment subgroups), exhibited NLRP3 inflammasome activation and IL-1ß secretion in cutaneous lesions, showing a trend in elevation to decline; NLRP3 mRNA expression reached a peak at 18 d in the BPG treatment subgroup and 21 d in the no BPG treatment subgroup and returned to "normal" levels [vs. the blank group (P > 0.05)] at 42 d post-infection. The trend was similar to the change in cutaneous lesions in the infected rabbits, which reached a peak at 16 d in the BPG treatment subgroup and 18 d in the no BPG treatment subgroup. NLRP3, caspase-1, and IL-1ß mRNA expression levels were slightly different in different organs. NLRP3 inflammasome activation was also observed in the kidney, liver, lung, spleen and testis. IL-1ß expression was observed in the kidney, liver, lung and spleen; however, there was no detectable level of IL-1ß in the testes of the infected rabbits. CONCLUSIONS: This study established a clear link between NLRP3 inflammasome activation and the development of tissue inflammation in rabbits infected with T. pallidum. BPG therapy imperceptibly adjusted syphilitic inflammation.


Asunto(s)
Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Sífilis/patología , Animales , Caspasa 1/genética , Caspasa 1/metabolismo , Inflamación/metabolismo , Inflamación/patología , Interleucina-1beta/análisis , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Riñón/metabolismo , Hígado/metabolismo , Masculino , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Penicilina G Benzatina/uso terapéutico , ARN Mensajero/metabolismo , Conejos , Sífilis/tratamiento farmacológico , Sífilis/microbiología , Sífilis/veterinaria , Treponema pallidum/genética , Treponema pallidum/aislamiento & purificación
17.
J Child Psychol Psychiatry ; 57(1): 74-83, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26072932

RESUMEN

BACKGROUND: Tourette syndrome (TS) is a common tic disorder in children and adolescents. There is preliminary evidence that herbal medicine may possess the potential to treat tics. The purpose of this study was to formally evaluate the efficacy and safety of 5-Ling Granule (5-LGr), a proprietary polyherbal product, for the treatment of patients with TS in comparison with tiapride and placebo. METHODS: In this multisite, double-blind, double-dummy, randomized, placebo-controlled trial, 603 patients with TS aged 5-18 years were randomly assigned to treatment with placebo (n = 117), tiapride (n = 123, 200-400 mg/day) or 5-LGr (n = 363, 15-22.5 g/day) for 8 weeks. The primary outcome was measured using the Yale Global Tic Severity Scale (YGTSS) and its subscales, total tic Score (TTS) and tic-related impairment. Incidence of adverse events was compared among the three groups. RESULTS: While tics of all patients were reduced over time, 5-LGr and tiapride treatment produced significantly greater improvement on the YGTSS overall scale and subscale for TTS and impairment at endpoint than the placebo. Seventy-four percentage of patients in the 5-LGr arm and 68.3% in the tiapride arm had clinical response and these rates of response were significantly higher than those on placebo (44.0%, p < .001). The incidence of overall adverse events was significantly fewer for patients on placebo and 5-LGr compared to tiapride (11.2% and 13.8% vs. 26.0%, p = .002); in particular physical tiredness, dizziness and sleep disturbance. CONCLUSIONS: The clinical efficacy of 5-LGr is comparable to tiapride in reducing tics. Its safety profile is better than tiapride. 5-LGr can be considered a safe and effective therapy for TS (Trial registration: www.clinicaltrials.gov: NCT01501695).

18.
Zhongguo Zhong Yao Za Zhi ; 41(16): 3100-3106, 2016 Aug.
Artículo en Chino | MEDLINE | ID: mdl-28920356

RESUMEN

To evaluate the efficacy and safety of Choudongning (CDN)capsule in children with Tourette's syndrome of spleen deficiency and phlegm accumulation through a randomized double-blind three-arm controlled phase Ⅲ study in 588 patients from 8 hospitals. The included patients were randomly divided into test group, positive control group and placebo group at the ratio of 3∶1∶1. Patients in the test group orally took CDN capsules and simulated Tiapridal tablets; the patients in positive control group took Tiapridal tablets and simulated CDN capsules; whereas the patients in placebo group orally took the simulated agents of the above two drugs. The treatment course was 6 weeks for three groups. The global grading rates, YGTSS scores and its factor scores, the degree of social function damage, as well as traditional Chinese medicine syndrome efficacy were evaluated as the outcome measures on efficacy. The AEs/ADRs, vital signs and laboratory testing were observed as outcome measures on safety. The total effective rate of YGTSS was 75.92% in the test group, 72.65% in the positive control group, and 37.29% in the placebo group. Non inferiority test stands between the test group and the positive control group, and they were superior to placebo group in efficacy with statistical difference. Significant difference had also been found among the 3 groups in YGTSS tics score, motor tics score, vocal tics, degree of social function damage and traditional Chinese medicine syndrome efficacy. During the study, there were 5 (1.42%)ADRs in the test group, 10 (8.55%)in the positive control group and 3 (2.54%)in the placebo group. The incidence of ADRs in the test group was lower than that in the positive control group, with statistical difference. It is clear to say that CDN capsule can effectively treat the Tourette's syndrome of spleen deficiency and phlegm accumulation. Its efficacy is not inferior to the commonly used Tiapridal tablets, with even less adverse reactions, so it has clinical application value.


Asunto(s)
Medicamentos Herbarios Chinos/uso terapéutico , Síndrome de Tourette/tratamiento farmacológico , Cápsulas , Niño , Método Doble Ciego , Humanos , Medicina Tradicional China , Bazo/fisiopatología , Resultado del Tratamiento
20.
J Neurol Sci ; 350(1-2): 79-83, 2015 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-25703276

RESUMEN

BACKGROUND: No gold standard currently exists for the diagnosis of general paresis (GP), thus often resulting in unnecessarily delayed therapeutic decision. METHODS: A retrospective chart review was performed for 85 inpatients with GP in Zhongshan Hospital, Medical College of Xiamen University, and the characteristics of their clinical profiles, serum and cerebrospinal fluid (CSF) examinations, neuroimaging examination, and electroencephalogram (EEG) data were analyzed. RESULTS: Among the 85 GP patients, the clinical symptoms that were frequently observed upon admission included a variety of psychiatric-behavioral symptoms and varying degrees of cognitive impairment. All of the patients had positive serum Treponema pallidum particle agglutination (TPPA) assays, 96.47% of the patients had positive CSF TPPA assays, and 41.18% of the patients had both CSF pleocytosis and elevated CSF protein levels. Focal atrophy in one cerebral region or in multiple regions was evident in neuroimages. The EEG data primarily showed slightly abnormal EEG activity. CONCLUSION: These results demonstrate the complexity of the clinical characteristics of GP and highlight the importance of early diagnosis.


Asunto(s)
Neurosífilis/sangre , Neurosífilis/diagnóstico , Treponema pallidum/aislamiento & purificación , Adulto , Anciano , Electroencefalografía/tendencias , Femenino , Humanos , Imagen por Resonancia Magnética/tendencias , Masculino , Persona de Mediana Edad , Neurosífilis/fisiopatología , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/tendencias
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