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Drug-resistant epilepsy is frequent, persistent, and brings a heavy economic burden to patients and their families. Traditional epilepsy detection methods ignore the causal relationship of seizures and focus on a single time or spatial dimension, and the effect varies greatly in different patients. Therefore, it is necessary to research accurate automatic detection technology of epilepsy in different patients. We propose a causal-spatio-temporal graph attention network (CSTGAT), which uses transfer entropy (TE) to construct a causal graph between multiple channels, combining graph attention network (GAT) and bi-directional long short-term memory (BiLSTM) to capture temporal dynamic correlation and spatial topological structure information. The accuracy, specificity, and sensitivity of the SWEZ dataset were 97.24%, 97.92%, and 98.11%. The accuracy of the private dataset reached 98.55%. The effectiveness of each module was proven through ablation experiments and the impact of different network construction methods was compared. The experimental results indicate that the causal relationship network constructed by TE could accurately capture the information flow of epileptic seizures, and GAT and BiLSTM could capture spatiotemporal dynamic correlations. This model accurately captures causal relationships and spatiotemporal correlations on two datasets, and it overcomes the variability of epileptic seizures in different patients, which may contribute to clinical surgical planning.
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BACKGROUND: Valproic acid (VPA) has been widely used to prevent epileptic seizures after neurosurgery in China. We have found that the incidence of liver injury (LI) in patients using VPA after neurosurgery is higher than that in other patients. OBJECTIVE: The objective of this study was to investigate the risk factors of LI in patients using VPA after neurosurgery. METHODS: A nested case-control study was conducted in patients using VPA after neurosurgery between September 2019 and March 2021. Cases of LI were matched to controls by age and body mass index (BMI). Conditional logistic regression was used to estimate matched odds ratios representing the odds of LI. A receiver operating characteristic curve was used to analyze the optimal cutoff condition. RESULTS: A total of 248 people (62 LI and 186 control) were enrolled. Among patients with vs without LI, the matched odds ratio for trough concentration of VPA was significant (matched odds ratio [OR], 1.09; 95% confidence interval [CI]: 1.01-1.19). The course of treatment (OR: 1.17, 95% CI: 1.02-1.33), Glasgow score (OR: 0.26, 95% CI: 0.10-0.67), gene polymorphisms of CYP2C19 (OR: 2.09, 95% CI: 1.03-146.93), and UGT1A6 (OR: 34.61, 95% CI: 1.19-1003.23) were all related to the outcome. The optimal cutoff of the course of treatment was 10 days, while the trough concentration of VPA was determined to be 66.16 mg/L. CONCLUSION: Length of treatment, VPA trough concentration, and Glasgow score were associated with LI in patients after neurosurgery. A gene test may be necessary for people who are prescribed VPA for a long time.
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Neurocirurgia , Ácido Valproico , Anticonvulsivantes/efeitos adversos , Estudos de Casos e Controles , Humanos , Fígado , Estudos Prospectivos , Ácido Valproico/efeitos adversosRESUMO
BACKGROUND: The goal of this study was to compare the efficacy and safety of needle-knife fistulotomy (NKF) to that of conventional cannulation methods (CCMs) when used for primary biliary access in patients with duodenal papillary tumors. METHODS: Consecutive patients who had duodenal papillary tumors and who underwent endoscopic retrograde cholangiopancreatography (ERCP) were retrospectively enrolled. Successful cannulation rates, cannulation and procedure times, and the prevalence of adverse events were compared between the NKF and CCM groups. RESULTS: A total of 404 patients (NKF, n = 124; CCM, n = 280) with duodenal papillary tumors were included. The primary and overall cannulation rates were 92.1% (372/404) and 96.0% (388/404), respectively. Compared to CCMs, NKF was associated with a significantly higher successful cannulation rate (99.2% versus 88.9%, P < 0.001) and significantly lower cannulation times (2.1 ± 2.0 min versus 4.7 ± 5.2 min), procedure times (8.8 ± 3.8 min versus 12.9 ± 7.6 min), and unintentional pancreatic duct cannulation rates (1.6% versus 20%), with P < 0.001 for all. Overall adverse events occurred less frequently in the NKF group (3.2% versus 10.7%, P = 0.011). Of these adverse events, post-ERCP pancreatitis (PEP) was significantly lower in the NKF group than in the CCM group (1.6% versus 6.8%, P = 0.03). Bleeding and cholangitis rarely occurred with either cannulation method (0.8% versus 2.1%, P = 0.681, and 0.8% versus 1.7%, P = 0.671, respectively). CONCLUSION: NKF is a more effective and safer procedure than CCMs for patients with duodenal papillary tumors.
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Neoplasias Duodenais , Esfinterotomia Endoscópica , Cateterismo/efeitos adversos , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Neoplasias Duodenais/cirurgia , Humanos , Estudos RetrospectivosRESUMO
Glioblastoma (GBM) is one of the most common aggressive cancers of the central nervous system in adults with a high mortality rate. Bortezomib is a boronic acid-based potent proteasome inhibitor that has been actively studied for its anti-tumour effects through inhibition of the proteasome. The proteasome is a key component of the ubiquitin-proteasome pathway that is critical for protein homeostasis, regulation of cellular growth, and apoptosis. Overexpression of polo-like kinase 4 (PLK4) is commonly reported in tumour cells and increases their invasive and metastatic abilities. In this study, we established a cell model of PLK4 knockdown and overexpression in LN-18, A172 and LN-229 cells and found that knockdown of PLK4 expression enhanced the anti-tumour effect of bortezomib. We further found that this effect may be mediated by the PTEN/PI3K/AKT/mTOR signalling pathway and that the apoptotic and oxidative stress processes were activated, while the expression of matrix metalloproteinases (MMPs) was down-regulated. Similar phenomenon was observed using in vitro experiments. Thus, we speculate that PLK4 inhibition may be a new therapeutic strategy for GBM.
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Bortezomib/farmacologia , Proliferação de Células/efeitos dos fármacos , Glioblastoma/tratamento farmacológico , Proteínas Serina-Treonina Quinases/genética , Animais , Apoptose/efeitos dos fármacos , Ácidos Borônicos/farmacologia , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glioblastoma/genética , Glioblastoma/patologia , Xenoenxertos , Humanos , Camundongos , PTEN Fosfo-Hidrolase/genética , Fosfatidilinositol 3-Quinases/genética , Inibidores de Proteassoma/farmacologia , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/genéticaRESUMO
OBJECTIVES: We evaluate the efficacy of concomitant therapy for Helicobacter pylori infection and the associated factors that influence it in China, where it has not previously been investigated. METHODS: In this prospective study, 374 consecutive patients with H. pylori infection were randomly assigned to 10 day regimens of concomitant therapy with different proton pump inhibitors: esomeprazole (20 mg)/omeprazole (20 mg), amoxicillin (1000 mg), clarithromycin (500 mg) and metronidazole (400 mg). All drugs were administered twice daily. A [(13)C]urea breath test was performed at least 4 weeks after the completion of treatment. Gene polymorphisms and antimicrobial susceptibility were determined. RESULTS: A total of 374 patients with active, uncomplicated duodenal ulcer disease were enrolled in the study (187 cases in each group). The overall eradication rate resulting from concomitant therapy was 90.7% (PP) and 86.1% (ITT) and the eradication rate was significantly higher in the group that received an esomeprazole-based regimen compared with the group that received an omeprazole-based regimen [95.4% versus 86.0%, respectively, Pâ=â0.003 (PP) and 89.8% versus 82.4%, Pâ=â0.036 (ITT), respectively]. Moreover, the omeprazole-based regimen was an independent risk factor for treatment failure (Pâ=â0.039), as were CYP2C19 extensive metabolizer (Pâ=â0.005), clarithromycin (Pâ=â0.000) and metronidazole resistance (Pâ=â0.000). In addition, CYP2C19 polymorphisms and antibiotic resistance had a synergistic effect on eradication rates. The majority of side effects were mild and none was serious. CONCLUSIONS: The 10 day concomitant therapy yielded an eradication rate of nearly 90%. Antibiotic resistance, CYP2C19 polymorphisms and their interactions were closely associated with regimen efficacy.
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Antibacterianos/uso terapêutico , Citocromo P-450 CYP2C19/genética , Farmacorresistência Bacteriana , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Polimorfismo Genético , Adulto , Testes Respiratórios , China , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Estudos Prospectivos , Inibidores da Bomba de Prótons/uso terapêutico , Resultado do Tratamento , Ureia/análiseRESUMO
OBJECTIVE: To explore the eradication efficacies of triple versus quadruple furazolidone-based regimens for Helicobacter pylori (H. pylori) infection. METHODS: A total of 357 outpatients with H. pylori infection were enrolled from June to December 2010. There were 200 males and 157 females with an average age of (42 ± 12) years. A diagnosis of duodenal ulcer was made according to their endoscopic examination results. They were randomly assigned into 4 treatment groups: 7-day triple (n = 89) and 10-day triple (n = 91), rabeprazole 10 mg, amoxicillin 1 000 mg and furazolidone 100 mg twice daily for 7 and 10 days respectively. 7-day quadruple (n = 88) and 10-day quadruple (n = 89), rabeprazole 10 mg, bismuth 220 mg, amoxicillin 1 000 mg and furazolidone 100 mg twice daily for 7 and 10 days respectively.H. pylori status was re-assessed with (14)C-urea breath test after 4-week therapy. RESULTS: Among them, 323 cases completed the study. According to the analysis of intention-to-treat (ITT), the H. pylori eradication rates were 71.91% (64/89) in 7-day triple, 81.32% (74/91) in 10-day triple, 78.41% (69/88) in 7-day quadruple and 83.15% (74/89) in 10-day quadruple groups. No significant deviation existed among all groups (P > 0.05). According the per-protocol (PP) analysis, H. pylori eradication rates were 78.05% (64/82) in 7-day triple, 88.10% (74/84) in 10-day triple, 87.34% (69/79) in 7-day quadruple and 94.87% (74/78) in 10-day quadruple groups. Significant deviation existed among all groups (P = 0.017). The H. pylori eradication rate in 10-day quadruple group was significantly higher than that in 7-day triple group (P = 0.002). The total adverse reaction rate was 7.00% (25/357). No significant difference existed among all groups (P > 0.05). CONCLUSIONS: Quadruple treatments provide higher H. pylori eradication rates than triple therapies. A 10-day treatment may improve H. pylori eradication rate. And 10-day quadruple regimen with furazolidone and bismuth may be effective for H. pylori infection.
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Antibacterianos/administração & dosagem , Furazolidona/administração & dosagem , Infecções por Helicobacter/tratamento farmacológico , Adolescente , Adulto , Idoso , Antibacterianos/uso terapêutico , Quimioterapia Combinada , Feminino , Furazolidona/uso terapêutico , Helicobacter pylori , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
The variability in the propagation pathway in epilepsy is a main factor contributing to surgical treatment failure. Ways to accurately capture the brain propagation network and quantitatively assess its evolution remain poorly described. This work aims to develop a dynamic step effective network (dSTE) to obtain the propagation path network of multiple seizures in the same patient and explore the degree of dissimilarity. Multichannel stereo-electroencephalography (sEEG) signals were acquired with ictal processes involving continuous changes in information propagation. We utilized high-order dynamic brain networks to obtain propagation networks through different levels of linking steps. We proposed a dissimilarity index based on singular value decomposition to quantitatively compare seizure pathways. Simulated data were generated through The Virtual Brain, and the reliability of this method was verified through ablation experiments. By applying the proposed method to two datasets consisting of 29 patients total, the evolution processes of each patient's seizure networks was obtained, and the within-patient dissimilarities were quantitatively compared. Finally, three types of brain network connectivity patterns were found. Type I patients have a good prognosis, while type III patients are prone to postoperative recurrence. This method captures the evolution of seizure propagation networks and assesses their dissimilarity more reliably than existing methods, demonstrating good robustness for studying the propagation path differences for multiple seizures in epilepsy patients. The three different patterns will be important considerations when planning epilepsy surgery under sEEG guidance.
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Epilepsia , Convulsões , Humanos , Reprodutibilidade dos Testes , Encéfalo , Eletroencefalografia/métodosRESUMO
Drug-resistant epilepsy with frequent seizures are considered to undergo surgery to become seizure-free, but seizure-free rates have not dramatically improved, partly due to imprecise intervention locations. To address this clinical need, we construct effective connectivity to reveal epilepsy brain dynamics. Based on the propagation path captured by the high order effective connectivity, calculate the control centrality evaluation scheme of the excised area. We used three datasets: simulation dataset, clinical dataset, and public dataset. The epileptogenic propagation network was quantified by calculating high-order effective connection to obtain accurate propagation path, based on this, combined with the outdegree index for virtual resection. By removing electrodes and recalculating control centrality, we quantify each electrode or region's control centrality to evaluate the virtual resection scheme. Three datasets obtained consistent results. We track the accurate propagation path and find the obvious inflection points occurring during the excision process. The minimum intervention targets were obtained by comparing different schemes without recurrence. The clinical data with multiple seizures found that after resection, the brain reaches a stable state and is less likely to continue spreading. By quantitative analysis of control centrality to evaluate the possible excision scheme, finally we obtain the best intervention area for epilepsy, which assist in developing surgical plans.
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Epilepsia Resistente a Medicamentos , Humanos , Epilepsia Resistente a Medicamentos/cirurgia , Epilepsia Resistente a Medicamentos/fisiopatologia , Masculino , Feminino , Eletroencefalografia/métodos , Encéfalo/cirurgia , Encéfalo/fisiopatologia , Adulto , Adulto Jovem , Adolescente , CriançaRESUMO
Over the past decade, infections linked to duodenoscopes have become a significant concern, primarily due to the intricate design of the elevator mechanism. Currently, there is limited evidence regarding the bacterial contamination level of the elevator mechanism after clinical use and throughout its various reprocessing stages. This study utilized the swab culture technique to examine the bacterial contamination on the duodenoscope elevator mechanism after clinical use and after 3 reprocessing stages at a Center of tertiary hospital. Our findings revealed severe bacterial contamination after clinical usage, emphasizing that the effectiveness of manual cleaning greatly influences the subsequent high-level disinfection quality.
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Duodenoscópios , Contaminação de Equipamentos , Humanos , Duodenoscópios/microbiologia , Bactérias , Desinfecção/métodosRESUMO
As a cutting-edge technology of connecting biological brain and external devices, brain-computer interface (BCI) exhibits promising applications on extensive fields such as medical and military. As for the disable individuals with four limbs losing the motor functions, it is a potential treatment way to drive mechanical equipments by the means of non-invasive BCI, which is badly depended on the accuracy of the decoded electroencephalogram (EEG) singles. In this study, an explanatory convolutional neural network namely EEGNet based on SimAM attention module was proposed to enhance the accuracy of decoding the EEG singles of index and thumb fingers for both left and right hand using sensory motor rhythm (SMR). An average classification accuracy of 72.91% the data of eight healthy subjects was obtained, which were captured from the one second before finger movement to two seconds after action. Furthermore, the character of event-related desynchronization (ERD) and event related synchronization (ERS) of index and thumb fingers was also studied in this study. These findings have significant importance for controlling external devices or other rehabilitation equipment using BCI in a fine way.
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Interfaces Cérebro-Computador , Eletroencefalografia , Dedos , Redes Neurais de Computação , Humanos , Dedos/fisiologia , Eletroencefalografia/métodos , Adulto , Masculino , Feminino , Adulto Jovem , Movimento/fisiologia , Encéfalo/fisiologiaRESUMO
INTRODUCTION: This study aimed to investigate the relationship between gene polymorphisms and clinical factors with the concentrations of valproic acid (VPA) in adult patients who underwent neurosurgery in China. METHODS: A total of 531 serum concentration samples at steady state were collected from 313 patients to develop a population pharmacokinetic (PPK) model. Data analysis was performed using nonlinear mixed effects modeling. Covariates included demographic parameters, biological characteristics, and genetic polymorphism. Bootstrap evaluation showed that the final model was stable. Sensitive analysis was performed to verify the relationship between gene polymorphisms and concentrations of VPA. Linear regression was used to analyze the relationship between VPA concentration, ANKK1, and daily dosage. RESULTS: In the recruited patients, 17 of 25 single-nucleotide polymorphism distributions were consistent with the Hardy-Weinberg equilibrium. A one-compartment model with first-order absorption and elimination was developed for VPA injections. VPA clearance was significantly influenced by three variables: sex (17.41% higher in male than female patients), body weight, and the ANKK1 gene. Typical values for the elimination clearance and the volume of central compartment were 0.614 L/min and 23.5 L, respectively. The model evaluation indicated the stable and precise performance of the final model. After sensitive analysis using Kruskal-Wallis and Mann-Whitney U tests, we found that patients with AA alleles had higher VPA concentrations than those with GG and AG alleles. Linear regression models showed that gene polymorphisms of ANKK1 had little effects on VPA concentration. CONCLUSION: A PPK model of VPA in Chinese Han patients was successfully established; this can be helpful for model-informed precision-dosing approaches in clinical patient care, and for exploring the mechanism of VPA-induced weight gain.
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BACKGROUND AND AIMS: Studies have indicated that endoscope reprocessing failure might be attributed to internal damage or residual liquid in endoscopes. However, large-sample survey data on the internal conditions of endoscopic channels after reprocessing are lacking. This study used a borescope to investigate the internal cleanliness and damage of 213 endoscopic biopsy channels after reprocessing at the endoscopy center of the First Affiliated Hospital of Nanchang University, provided in theoretical basis for the efficacy of endoscope reprocessing and maintenance. METHODS: A borescope was used to observe and analyze the inside of the endoscopic biopsy channel of 213 reprocessed endoscopes (in accordance with the Chinese health industry standard "Regulation for cleaning and disinfection technique of flexible endoscope (WS 507-2016). Each endoscope was observed for at least 10 minutes, and the results were recorded and evaluated by 5 researchers independently. RESULTS: In all, 2504 images and 109 videos were recorded, and abnormal findings were classified into 10 categories: scratches (91.5%, 195/213), scratches with adherent peel (46.0%, 98/213), discolored areas (49.3%, 105/213), transparent drops (28.2%, 60/213), milky drops (23.9%, 51/213), white particles (46.9%, 100/213), attached materials (37.6%, 80/213), wear on metal parts (41.3%, 88/213), rust (23.9%, 51/213), and black spots (35.7%, 76/213). Among scratches, those in Teflon from 0-10 cm at the apex of the biopsy channel outlet and in metal from 0-5 cm at the biopsy channel inlet accounted for 58.4% (114/195) and 96.4% (188/195), respectively. CONCLUSIONS: Scratches were the most common form of damage in the endoscopic biopsy channels investigated and were related to the use of endoscopic accessories and cleaning brush materials. The incidence of other abnormalities gradually increased with the duration of use and began to increase significantly after 18 months. All abnormalities have a certain impact on the quality of endoscope reprocessing. We recommend that a borescope be used to check the inside of endoscopic biopsy channels regularly to determine the damage and cleaning conditions and that these channels be reprocessed, repaired, or replaced in a timely manner.
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Desinfecção , Endoscópios , Humanos , Desinfecção/métodos , Endoscopia , Contaminação de Equipamentos/prevenção & controleRESUMO
Addressing pancreaticobiliary disorders concomitant with gastroesophageal varices remains challenging. The goal of this study was to evaluate and compare the efficacy and safety of endoscopic retrograde cholangiopancreatography (ERCP) in cirrhotic and noncirrhotic patients with gastroesophageal varices.We retrospectively analyzed the data of consecutive patients with gastroesophageal varices who underwent ERCP.Two hundred seventy ERCP procedures were performed on 208 patients. The overall technical success rate was 98.5%, and no difference was found between cirrhotic and noncirrhotic patients (98.7% vs 97.7%, Pâ=â.511); of these, endoscopic retrograde biliary drainage, endoscopic metal biliary endoprosthesis placement, endoscopic retrograde pancreatic drainage, and stone extraction were conducted in 173/270 (64.1%), 27/270 (10.0%), 26/270 (9.6%), and 116/270 (43.0%) cases, respectively. Endoscopic retrograde biliary drainage and stone extraction were more frequently performed in cirrhotic cases (67.7% versus 45.5%, Pâ=â.005; 46.5% versus 25.0%, Pâ=â.009, respectively), while the noncirrhotic group had significantly higher rates of endoscopic metal biliary endoprosthesis placement (31.8% versus 5.8%, Pâ=â.000) and endoscopic retrograde pancreatic drainage (18.2% versus 8.0%, Pâ=â.036) than the cirrhotic group. The overall rate of adverse events was 21.1%, including fever (6.7%), post-ERCP pancreatitis ( 3.0%), hyperamylasemia (6.3%), duodenal papilla bleeding (3.3%), cardiac mucosal laceration (1.1%), and perforation (0.4%). No differences in any of the adverse events were found between the 2 groups. Additionally, gastroesophageal variceal bleeding occurred in 1 patient with grade III varices 7 days after ERCP.ERCP may be effective and safe for patients with gastroesophageal varices, irrespective of the etiologies caused by liver cirrhosis.
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Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Varizes Esofágicas e Gástricas/cirurgia , Cirrose Hepática/complicações , Adulto , Idoso , Varizes Esofágicas e Gástricas/etiologia , Feminino , Humanos , Hipertensão Portal/complicações , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Estudos RetrospectivosRESUMO
It remains challenging for endoscopists to manage pancreaticobiliary diseases in patients with ectopic papilla of Vater by endoscopic retrograde cholangiopancreatography (ERCP). The present study sought to evaluate the efficacy and safety of ERCP for this issue.Consecutive patients with ectopic papilla of Vater who underwent initial ERCP due to pancreaticobiliary diseases were retrospectively analyzed.One hundred seven patients with ectopic papilla of Vater were included. The success rate of cannulation was 83.2%. Endoscopic sphincterotomy, endoscopic papillary balloon dilation, and mechanical lithotripsy were performed in 12 (11.2%), 25 (23.4%), and 1 (0.9%) patients, respectively. The technical success rate was 83.2%; of these, endoscopic nasobiliary drainage, endoscopic retrograde biliary drainage, endoscopic retrograde pancreatic drainage, and stone extraction was conducted in 61 (57.0%), 17 (15.9%), 5 (4.7%), and 45 (42.1%) patients, respectively. Bile duct stone size ≥1âcm, number ≥2, and duodenum stenosis were risk factors for stone extraction inability. Adverse events occurred in 20 (18.7%) patients, including post-ERCP pancreatitis (3.7%), hyperamylasemia (12.1%), and infection of biliary tract (2.8%); all of the adverse events were mild and alleviated by conventional therapies.ERCP is an appropriate choice for pancreaticobiliary diseases in patients with ectopic papilla of Vater due to its high efficacy and safety. Bile duct stone size ≥1âcm, number ≥2, and duodenum stenosis increase difficulties for stone extraction.
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Ampola Hepatopancreática , Doenças Biliares/cirurgia , Colangiopancreatografia Retrógrada Endoscópica/métodos , Coristoma/cirurgia , Duodenopatias/cirurgia , Pancreatopatias/cirurgia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
Glioma is the most frequent and aggressive primary tumor of the brain in humans. Over the last few decades, significant progress has been made in early detection and multi-mode treatments, but the prognosis of gliomas is still extremely poor. MicroRNAs are endogenously expressed non-coding, single strand and short RNA molecules. Increasing number of studies demonstrated that microRNAs are dysregulated in a variety of human cancers, and play significant roles in tumorigenesis and tumor development, including glioma. In the present study, we for the first time found that microRNA-302a (miR-302a) was significantly downregulated in both glioma tissues and cell lines. In glioma patients, low miR-302a expression was correlated with KPS score and WHO grade. Restoration of miR-302a expression inhibited cell proliferation, migration and invasion of glioma in vitro. In addition, GAB2 was identified as a direct target of miR-320a. In clinical glioma tissues, GAB2 was upregulated and in-versely correlated with miR-302a expression. GAB2 underexpression had similar biological roles with miR-302a overexpression in glio-ma cells, further confirming that GAB2 was a functional downstream target of miR-302a. Moreover, rescue experiments showed that upregulation of GAB2 effectively reversed the inhibition effects of miR-302a on glioma cells proliferation, migration and invasion. These findings suggested that miR-302a is an important tumor suppressor of glioma progression by directly targeting GAB2, thus providing new insight into the molecular mechanisms underlying glioma occurrence, development and evolution of glioma.
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Proteínas Adaptadoras de Transdução de Sinal/genética , Neoplasias Encefálicas/patologia , Glioma/patologia , MicroRNAs/genética , Regiões 3' não Traduzidas , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Idoso , Neoplasias Encefálicas/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Glioma/genética , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Glioma is the most common form of malignant brain cancer with high mortality rate in human. Therefore, finding effective therapeutic strategy and revealing the underlying molecular mechanism is necessary. Plant-extracted flavonoid glycosides have been suggested to be bioactive compounds with pleiotropic functions, such as anti-cancer, anti-inflammatory, antioxidant and effects. Our study was attempted to explore the anti-cancer role of linarin (acacetin-7-O-ß-d-rutinoside) in glioma in vitro and in vivo. Nuclear factor kappa-B (NF-κB) activity is a common phenomenon in various cancers, resulting in abnormal cell proliferation, malignant transformation, or resistance to cell death. P53, an essential tumor suppressor, plays an important role in preventing tumor progression. Our data indicated that linarin suppressed glioma cell proliferation and migration by inducing apoptosis, which was through reducing cell cycle-related signals, including Survivin, p-Rb, and Cyclin D1, while promoting p21, Bax, Caspase-3 and poly (ADP-ribose) polymerase (PARP) activation. Also, we found that linarin-reduced cellular proliferation of glioma was dependent on p53 up-regulation and Nuclear factor kappa-B (NF-κB)/p65-down-regulation, thereby inhibiting glioma cell growth. We further conformed the inhibitory effect of linarin in vivo using xenograft tumor model. Linarin significantly triggered apoptosis as well as the tumor growth in animals, accompanied with p53 increase and p65 decrease. Our data illustrated that linarin could be used as a promising candidate against glioma progression.
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Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/metabolismo , Glioma/tratamento farmacológico , Glioma/metabolismo , Glicosídeos/uso terapêutico , Fator de Transcrição RelA/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Regulação para Cima , Animais , Apoptose/efeitos dos fármacos , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/ultraestrutura , Caspase 3/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Glioma/patologia , Glioma/ultraestrutura , Glicosídeos/farmacologia , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Transdução de Sinais/efeitos dos fármacos , Ensaio Tumoral de Célula-Tronco , Regulação para Cima/efeitos dos fármacosRESUMO
AIM: To evaluate the efficacy of furazolidone-based triple and quadruple therapy in eradicating Helicobacter pylori (H. pylori) in a multi-center randomized controlled trial. METHODS: A total of 720 H. pylori positive patients with duodenal ulcer disease were enrolled at 10 different hospitals in Jiangxi province in China. The patients were randomly assigned to four treatment groups as follows: patients in Groups 1 and 3 received rabeprazole (10 mg), amoxicillin (1000 mg) and furazolidone (100 mg) twice daily for 7 and 10 d, respectively; patients in Groups 2 and 4 received rabeprazole (10 mg), bismuth (220 mg), amoxicillin (1000 mg) and furazolidone (100 mg) twice daily for 7 and 10 d, respectively. The primary outcome measure was H. pylori eradication rate 4 wk after treatment by intention-to-treat and per protocol analysis, while the secondary outcome measures were symptom and sign changes at the end of treatment and 4 wk after the end of treatment, as well as the proportion of patients who developed adverse events. RESULTS: The demographic data of the four groups were not significantly different. Overall, 666 patients completed the scheme and were re-assessed with the (13)C-urea breath test. The intention-to-treat analysis of the H. pylori eradication rates in Groups 1, 2, 3 and 4 were 74.44%, 82.78%, 78.89% and 86.11%, respectively. The H. pylori eradication rate in Group 4 was significantly higher than that in Group 1. According to the per protocol analysis, the H. pylori eradication rates in Groups 1, 2, 3 and 4 were 81.21%, 89.22%, 85.54% and 92.26%, respectively. The H. pylori eradication rate in Group 4 was significantly higher than that in Group 1. The number of adverse events was 15 (8.3%), 16 (8.9%), 15 (8.3%) and 17 (9.4%) in Groups 1, 2, 3 and 4, respectively, including dizziness, vomiting, diarrhea, nausea, skin rash, itchy skin, and malaise. The symptoms were relieved without special treatment in all of the patients. CONCLUSION: Both 7- and 10-d quadruple furazolidone-based therapies achieve satisfactory H. pylori eradication rates.
Assuntos
Antibacterianos/uso terapêutico , Úlcera Duodenal/tratamento farmacológico , Furazolidona/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Adulto , Amoxicilina/uso terapêutico , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , China , Esquema de Medicação , Quimioterapia Combinada , Úlcera Duodenal/diagnóstico , Úlcera Duodenal/microbiologia , Feminino , Furazolidona/administração & dosagem , Furazolidona/efeitos adversos , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/microbiologia , Helicobacter pylori/patogenicidade , Humanos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Compostos Organometálicos/uso terapêutico , Inibidores da Bomba de Prótons/uso terapêutico , Rabeprazol/uso terapêutico , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND AND OBJECTIVE: In cases of ascites of unknown etiology, tuberculosis peritonitis (TBP) is a possible cause but a diagnostic challenge. This retrospective case series assessed the effectiveness and safety of diagnostic natural orifice translumenal endoscopic surgery (NOTES(®); American Society for Gastrointestinal Endoscopy [Oak Brook, IL] and the Society of American Gastrointestinal and Endoscopic Surgeons [Los Angeles, CA]) in 7 consecutive patients with suspected TBP. SUBJECTS AND METHODS: Between September 2011 and August 2012, peritoneal biopsy was performed using transgastric NOTES for subsequent histology in 7 consecutive hospitalized patients who presented with ascites and were diagnosed with suspected TBP. The outcome measures included diagnostic accuracy and procedure-related morbidities. RESULTS: Diagnostic NOTES was successfully completed in all 7 patients. Peritoneoscopy with NOTES went uneventfully and lasted 5-10 minutes. Typical peritoneal nodules characteristic of TBP were identified in all patients and confirmed pathologically as TBP. No clinically significant adverse events occurred in any patients following NOTES, except for 1 patient who experienced mild and transient pyrexia. Postoperative blood culture detected no microbial growth. Follow-up upper gastrointestinal endoscopy showed that the gastric wall wound healed well with minimal scarring. All patients were prescribed a standard four-drug antituberculosis chemotherapy regimen. The treatment outcomes were determined to be effective or curative, and no relapse was detected within the follow-up period. CONCLUSIONS: NOTES is an effective and safe diagnostic technique in patients with suspected TBP presenting as ascites of unknown etiology.
Assuntos
Cirurgia Endoscópica por Orifício Natural , Peritonite Tuberculosa/diagnóstico , Peritonite Tuberculosa/cirurgia , Adolescente , Adulto , Ascite/diagnóstico , Ascite/cirurgia , Biópsia , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumoperitônio Artificial , Estudos Retrospectivos , Resultado do TratamentoRESUMO
In present study, in vivo electrophysiological techniques were applied to examine the effects of anterior cingulate cortex (ACC) activation on mechanical and electrical stimuli-evoked responses in rat spinal cord wide-dynamic-range (WDR) neurons. We found that bilateral ACC electrical stimulation (100Hz, 20V, 20s) had different effects on neuronal responses to brush, pressure and pinch stimuli (10s). The brush-evoked neuronal responses at baseline, post 1min and post 5min were 60.8±15.0, 59.2±15.4 and 60.0±19.3 spikes/10s, respectively (n=10, P>0.05 vs. baseline). The pressure-evoked neuronal responses at baseline, post 1min and post 5min were 77.8±11.9, 38.0±7.8 and 45.8±7.6 spikes/10s, respectively (n=10, P<0.05 vs. baseline). The pinch-evoked neuronal responses at baseline, post 1min and post 5min were 137.6±16.7, 62.6±17.5 and 68.8±15.0 spikes/10s, respectively (n=10, P<0.05 vs. baseline). Furthermore, ACC stimulation generated distinct effects on the different components of wind-up response. The total numbers of late response (LR) and after-discharge (AD), but not early response (ER), significantly decreased. Collectively, the present study demonstrated that short-term ACC activation could generate long-term inhibitory effects on the responses of WDR neurons to noxious mechanical (pressure and pinch) and electrical stimuli. The results indicated that ACC activation could negatively regulate noxious information ascending from spinal cord with long-term effect, providing potential neuronal substrate for the modulation of ACC activation on nociception.
Assuntos
Giro do Cíngulo/fisiologia , Neurônios/fisiologia , Medula Espinal/fisiologia , Animais , Masculino , Nociceptores/fisiologia , Estimulação Física , Ratos , Ratos Sprague-DawleyRESUMO
We studied the effect of stereotactic surgery in cases of alcohol dependence. Twelve patients with a psychological dependence on alcohol (treated systematically with medication for detoxification 3-8 times in various rehabilitation centers before, but had relapsed within 2 weeks after withdrawal) were treated by ablating the nucleus accumbens (NA(C)) bilaterally using stereotactic surgery. The therapeutic effect and safety evaluation index of the surgery were analyzed. The timing of the conducted evaluations was preoperatively and in the sixth postoperative month. Currently, relapse has not occurred in 9 cases. Relapse occurred in 3 cases after surgery. The prevalence of relapse was 16.7% within 6 months, and 25% within 12 months. Non-specific complications of this type of surgery (e.g., intracranial hematoma, infection) were not observed. One case in 12 patients suffered dysosmia, but he recovered completely 4 months later after surgery. The full-scale intelligence quotient (FSIQ) and memory quotient (MQ) of these patients were significantly improved 6 months postoperatively compared with preoperatively. The severity of alcohol dependence scale and a scale measuring alcohol craving in these patients were significantly decreased. There were also significant changes over time in the Minnesota multiphasic personality inventory (MMPI) profile, suggesting a decrease in depression, irritability, and psychopathy. Ablating specified targets (NA(C)) using stereotactic surgery is a safe method to alleviate alcohol craving, reduce relapse rates and improve quality-of-life in patients with psychological dependence on alcohol.