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RATIONALE: Polyarteritis nodosa (PAN) is a necrotizing vasculitis that affects small- and medium-sized arteries, presenting with diverse clinical manifestations. It can impact tissues and organs throughout the body and may be life-threatening in severe cases. Common causes of death include cardiac, renal, and gastrointestinal complications or aneurysm rupture. While separate reports of renal aneurysm and intestinal perforation exist, the coexistence of these conditions is rarely documented. This study reports a severe case of PAN complicated by both renal aneurysm and intestinal perforation, aiming to deepen the understanding of this disease, aid in clinical diagnosis and treatment, and improve patient prognosis. PATIENT CONCERNS: The patient presented to the hospital with dorsal foot pain and abdominal pain persisting for more than 4 months, along with pain and discomfort in both lower extremities for over 1 month. INTERVENTIONS: The patient was diagnosed with PAN, renal aneurysm, intestinal perforation, and grade 3 hypertension (high risk). OUTCOMES: After treatment, the patient showed normal temperature and blood pressure, relief from abdominal pain, and disappearance of myalgia and numbness in the lower limbs. Additionally, the renal aneurysm shrank significantly, the intestinal perforation healed, the ileostomy was reduced, and the patient's condition stabilized. LESSONS: The clinical symptoms of PAN mostly lack specificity, and should be distinguished from microscopic polyangiitis and simulated vasculitis. For patients with intestinal perforation similar to this case, tocilizumab treatment may be effective, but further research is needed to confirm it.
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Perfuração Intestinal , Poliarterite Nodosa , Humanos , Poliarterite Nodosa/complicações , Poliarterite Nodosa/diagnóstico , Perfuração Intestinal/etiologia , Perfuração Intestinal/diagnóstico , Aneurisma/etiologia , Aneurisma/complicações , Aneurisma/diagnóstico , Artéria Renal , Masculino , Feminino , Pessoa de Meia-Idade , Dor Abdominal/etiologiaRESUMO
To investigate the endothelialization of covered and bare stents deployed in the canine carotid arteries and subclavian arteries for treating experimental aneurysms and arteriovenous fistulas, twenty aneurysms were created in 10 dogs, and 20 fistulas in another 10 dogs. The Willis balloon-expandable covered stent and a self-expandable covered stent were used to treat these lesions, and a self-expandable bare stent was deployed in the subclavian artery for comparison. Followed up for up to 12 months, the gross observation, pathological staining, and scanning electronic microscopic data were analyzed. Two weeks after creation of animal model, thirty self-expandable covered stents and ten balloon-expandable covered stents were deployed. Fifteen bare stents were deployed within the left subclavian arteries. Twenty days after stenting, the aneurysm significantly shrank. At 6 months, the thrombi within the aneurysm cavity were organized. Three to 12 months later, most covered and bare stents were covered by a thin transparent or white layer of endothelial intima. Layers of intima or pseudomembrane were formed on the stent 20-40 days after stent deployment. Over three months, the pseudomembrane became organized, thinner, and merged into the vascular wall. Under scanning electronic microscopy, the surface of covered and bare stents had only deposition of collagen fibers and rare endothelial cells 20-40 days after stenting. From three to ten months, the endothelial cells on the internal surface of stent became mature, with spindle, stripe-like or quasi round morphology along the blood flow direction. Over time, the endothelial cells became mature. In conclusion, three months after deployment in canines' arteries, the self-expandable bare and covered stents have mostly been covered by endothelial cells which become maturer over time, whereas the balloon-expandable covered stents do not have complete coverage of endothelial cells at three months, especially for protruding stent struts and areas. Over time, the endothelialization will become mature.
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Aneurisma , Fístula Arteriovenosa , Cães , Animais , Células Endoteliais , Aneurisma/cirurgia , Aneurisma/patologia , Stents/efeitos adversos , Artérias Carótidas/cirurgia , Artérias Carótidas/patologia , Fístula Arteriovenosa/patologia , PolitetrafluoretilenoRESUMO
The role of Galectin-9 (Gal-9) in the pathogenesis of rheumatoid arthritis (RA) remains unclear. This study aimed to investigate the mechanism of action and therapeutic potential of Gal-9 in RA. We detected Gal-9 expression in clinical samples, explored the mechanism of function of Gal-9 by knockdown and overexpression in fibroblast-like synoviocytes (FLSs), and further verified it in collagen-induced arthritis (CIA) model. We found that the levels of Gal-9 were considerably elevated in RA synovium than in osteoarthritis (OA) patients. A substantial decrease of Gal-9 was demonstrated after tumor necrosis factor (TNF-α) inhibitor treatment in the plasma of patients with RA. Additionally, transcriptome sequencing revealed that Gal-9 was involved in the regulation of the TNF-α pathway. Gal-9 was considerably upregulated after TNF-α stimulation in FLSs, and knockdown of Gal-9 substantially inhibited TNF-α activated proliferation, migration and inflammatory response. According to cell transcriptome sequencing results, we further confirmed that Gal-9 could achieve these effects by interacting with MAFB and affecting PI3K/AKT/mTOR pathway. Finally, we knocked down Gal-9 on the CIA model and found that it could alleviate the progression of arthritis. In conclusion, our study revealed that the knockdown of Gal-9 could inhibited TNF-α induced activation in RA through MAFB, PI3K/AKT/mTOR.
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Artrite Experimental , Artrite Reumatoide , Sinoviócitos , Animais , Humanos , Artrite Experimental/metabolismo , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/genética , Artrite Reumatoide/metabolismo , Proliferação de Células , Células Cultivadas , Fibroblastos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Sinoviócitos/patologia , Serina-Treonina Quinases TOR/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
RATIONALE: A chronic autoimmune liver disease known as primary biliary cholangitis (PBC) that selectively destructs small intrahepatic biliary epithelial cells and may result in biliary cirrhosis and eventually liver transplantation or death. PBC is associated with various other extrahepatic autoimmune diseases; however, the combination of PBC with ankylosing spondylitis has been rarely reported in the literature. Here, we reported a case of PBC with ankylosing spondylitis to improve our understanding of such coexistence and provide new ideas for the treatment of such patients. PATIENT CONCERNS: A 54-year-old man was presented to the Department of Rheumatology because of an abnormal liver function test for 7 years, chest and back pain for 1 year, and low back pain for 2 months. DIAGNOSES: Primary biliary cholangitis, ankylosing spondylitis, and old pulmonary tuberculosis. INTERVENTIONS: The patient refused to use nonsteroidal anti-inflammatory drugs, conventional synthetic disease-modifying antirheumatic drugs, and biologic disease-modifying antirheumatic drugs; thus, he was treated with methylenediphosphonate (99Tc-MDP) and ursodeoxycholic acid (UDCA). OUTCOMES: The patient achieved remission with UDCA and 99Tc-MDP therapy. LESSONS: In the treatment of PBC combined with other disorders, the characteristics of different diseases should be considered. The patient reported herein was treated with 99Tc-MDP and UDCA, and his condition improved; thus, we consider 99Tc-MDP to be an effective treatment. Furthermore, in line with the current understanding of the pathogenesis of PBC and ankylosing spondylitis, we hypothesize that interleukin-17 inhibitor is an effective treatment for such patients.
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Antirreumáticos , Doenças Autoimunes , Colangite , Cirrose Hepática Biliar , Espondilite Anquilosante , Masculino , Humanos , Pessoa de Meia-Idade , Espondilite Anquilosante/complicações , Espondilite Anquilosante/tratamento farmacológico , Ácido Ursodesoxicólico/uso terapêutico , Doenças Autoimunes/tratamento farmacológico , Antirreumáticos/uso terapêutico , Colangite/complicações , Colangite/tratamento farmacológico , Colagogos e Coleréticos/uso terapêuticoRESUMO
This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief. It includes data and figures from patients that were cared for by Dr. Malek at the Cerebrovascular Hemodynamics laboratory in the Department of Neurosurgery at Tufts Medical Center. The Editor-in-Chief has been informed by Tufts Medical Center that the authors of the paper did not have clinical privileges for these patients and played no clinical role in their care.
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It is very important to treat adenomyosis which may cause infertility, menorrhagia, and dysmenorrhea for women at the reproductive age. High-intensity focused ultrasound (HIFU) is effective in destroying target tumor tissues without damaging the path of the ultrasound beam and surrounding normal tissues. The levonorgestrel-releasing intrauterine system (LN-IUS) is a medical system which is inserted into the uterine to provide medicinal treatment for temporary control of the symptoms caused by adenomyosis. This study was to investigate the effect of HIFU combined with the LN-IUS on adenomyosis. In the HIFU treatment, the parameters of the ultrasound were transmission frequency 0.8 MHz and input power 50-400 W (350 ± 30), and the temperature in the target tissue under these conditions would reach 60-100 °C (85 °C ± 6.3 °C). Size reduction and blood flow signal decrease were used to assess the effect of combined treatment. In this study, 131 patients with adenomyosis treated with HIFU combined with LN-IUS were retrospectively enrolled. The clinical and follow-up data were analyzed. After treatment, the volume of the uterine lesion was significantly decreased with an effective rate of 72.1%, and the adenomyosis blood flow signals were significantly reduced, with an effective rate of 71.3%. At six months, the menstrual cycle was significantly (P < 0.05) decreased from 31.4 ± 3.5 days before treatment to 28.6 ± 1.9 days, the menstrual period was significantly shortened from 7.9 ± 1.2 days before HIFU to 6.5 ± 1.3 days, and the menstrual volume was significantly (P < 0.05) decreased from 100 to 49% ± 13%. The serum hemoglobin significantly (P < 0.05) increased from 90.8 ± 6.2 g/L before treatment to 121.6 ± 10.8 g/L at six months for patients with anemia. Among seventy-two (92.3%) patients who finished the six-month follow-up, sixty-five (90.3%) patients had the dysmenorrhea completely relieved, and the other seven (9.7%) patients had only slight dysmenorrhea which did not affect their daily life. Adverse events occurred in 24 (18.3%) patients without causing severe consequences, including skin burns in two (1.5%) patients, skin swelling in four (3.1%), mild lower abdominal pain and low fever in 15 (11.5%), and subcutaneous induration in three (2.3%). Six months after treatment, no other serious side effects occurred in any patients with follow-up. In conclusions, the use of high-intensity focused ultrasound combined with the levonorgestrel-releasing intrauterine system for the treatment of adenomyosis is safe and effective even though the long-term effect remains to be confirmed.
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Adenomiose , Humanos , Feminino , Adenomiose/terapia , Adenomiose/patologia , Levanogestrel/farmacologia , Dismenorreia/terapia , Dismenorreia/etiologia , Estudos Retrospectivos , Útero/patologiaRESUMO
OBJECTIVE: Pyroptosis is crucial to rheumatoid arthritis (RA) by inducing and aggravating inflammation. TNF-α is abundant in fibroblast-like synoviocytes of RA (RA-FLSs) and plays a key role in pyroptosis by inducing nuclear factor (NF)-κB activation. Additionally, interleukin (IL)-37 is involved in autoimmune diseases as an anti-inflammatory cytokine and innate and acquired immune response inhibitor. However, the effect of IL-37 on pyroptosis in RA-FLSs remains unclear. Therefore, this study investigated the effects and mechanism of IL-37 on RA-FLS pyroptosis induced by TNF-α. METHODS: In this study, the serum cytokines in patients with RA and healthy controls were detected using ELISA. The RA-FLSs were then cultured with TNF-α, with or without various IL-37 concentrations, to test the cytokine levels in the cell supernatant. 5-Ethynyl-2'-Deoxyuridine (EdU) assay assessed the effects of IL-37 on RA FLS proliferation. RA-FLS apoptosis was assessed using flow cytometry and mitochondrial membrane potential (MMP) measurement. In addition, transmission electron microscopy (TEM) was used to examine cell pyroptosis. We selected the optimal concentration for the following experiments and detected the signal pathway of IL-37 on pyroptosis of RA FLSs by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and Western blotting. Finally, we validated the therapeutic effects of IL-37 on CIA rat model in vivo. RESULTS: IL-37 inhibited inflammation in vitro and in vivo and reduced pyroptosis-related protein expression in RA FLSs. Furthermore, we determined that nuclear factor κB (NF-κB) signaling is required for GSDMD-mediated pyroptosis in RA FLSs. CONCLUSION: IL-37 alleviates TNF-α-induced pyroptosis of RA FLSs by inhibiting NF-κB/GSDMD signaling. Additionally, our data revealed a novel mechanism for IL-37 in RA FLSs, suggesting a new potential therapy for IL-37 to treat RA.
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Artrite Reumatoide , Sinoviócitos , Ratos , Animais , NF-kappa B/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Piroptose , Transdução de Sinais , Artrite Reumatoide/metabolismo , Inflamação/metabolismo , Citocinas/metabolismo , Fibroblastos , Células Cultivadas , Proliferação de CélulasRESUMO
The effect and safety of endovascular treatment of basilar tip aneurysms associated with moyamoya disease are unknown. This study was to investigate the safety and effect of endovascular treatment of basilar tip aneurysms associated with moyamoya disease. Patients with moyamoya disease concurrent with basilar tip aneurysms were retrospectively enrolled and treated with endovascular embolization. The clinical and angiographic data were analyzed. Thirty patients with a basilar tip aneurysm were enrolled, including 8 (26.67%) male and 22 (73.33%) female patients aged 38 to 72 years (mean 54.4 ± 8.15). Endovascular treatment was successfully performed in 29 (96.67%) patients but failed in 1 (3.33%). Immediately after embolization, aneurysm occlusion degree was Raymond-Roy grade I in 26 (89.66%), grade II in 2 (6.90%), and grade III in 1 (3.45%). Intraprocedural complications occurred in 2 (10%) patients, including aneurysm rupture in 1 (3.33%), leading to death of the patient, and stent thrombosis in 2 (6.67%) which was successfully treated with thrombolysis. At discharge, good clinical outcome (modified Rankin Scale 0-2) was achieved in 29 (96.67%) and death in 1 (3.03%). Follow-up was performed 6 to 26 months (median 15) in 27 (93.1%) patients. Aneurysm occlusion degree was Raymond-Roy grade I in 21 (77.78%) patients, grade II in 4 (14.81%), and grade III in 2 (7.41%), not significantly (P = .67) different from those immediately after embolization. Aneurysm recurrence was found in 4 patients (14.81%). The clinical outcome was modified Rankin Scale 0 to 2 in all 27 patients, not significantly different from that at discharge. Endovascular embolization can be performed safely and effectively for basilar tip aneurysms associated with moyamoya disease even though more advanced embolization techniques are necessary.
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Embolização Terapêutica , Procedimentos Endovasculares , Aneurisma Intracraniano , Doença de Moyamoya , Humanos , Masculino , Feminino , Resultado do Tratamento , Estudos Retrospectivos , Aneurisma Intracraniano/terapia , Aneurisma Intracraniano/complicações , Doença de Moyamoya/complicações , Doença de Moyamoya/terapia , Embolização Terapêutica/efeitos adversos , Embolização Terapêutica/métodos , Angiografia Cerebral/métodos , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/métodos , StentsRESUMO
OBJECTIVE: Examine patterns of dual use of cigarettes and smokeless tobacco and complete switching over time among adult current cigarette smokers using data from the Population Assessment of Tobacco and Health Study Wave 3 (2015-2016), Wave 4 (2016-2018) and Wave 5 (2018-2019). METHODS: We examined four tobacco use states among 6834 exclusive smokers and 372 dual users at Wave 3 with two waves of follow-up data: exclusive cigarette use, exclusive smokeless tobacco use, dual use and use of neither product. RESULTS: Among exclusive smokers at Wave 3, only 1.6% (95% CI: 1.3% to 2.1%) transitioned to dual use at Wave 4, and 0.1% (95% CI: 0.07% to 0.2%) switched to exclusive smokeless tobacco use. Among exclusive smokers who switched to dual use, 53.1% (95% CI: 40.9% to 64.9%) returned to exclusive cigarette smoking, 34.3% (95% CI: 23.8% to 46.6%) maintained dual use and 12.6% (95% CI: 7.0% to 21.7%) did not smoke cigarettes after an additional wave of follow-up. Dual users at Wave 3 were likely to maintain their dual use status at Wave 4, 51.2% (95% CI: 46.1% to 56.3%) and Wave 5, 47.9% (95% CI: 40.1% to 55.8%). CONCLUSIONS: Very few cigarette smokers transition to smokeless tobacco use, and among those who do, dual use is more common than exclusive smokeless tobacco use. Further, the majority of exclusive cigarette smokers who transition to dual use at Wave 4 continue smoking cigarettes at Wave 5, either as dual users or as exclusive smokers.
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Sistemas Eletrônicos de Liberação de Nicotina , Produtos do Tabaco , Tabaco sem Fumaça , Adulto , Humanos , Estados Unidos , Fumantes , Nicotiana , Uso de Tabaco/epidemiologiaRESUMO
PURPOSE: To examine whether survey setting was associated with youth reporting of current (past 30-day) use of any tobacco product, e-cigarettes, cigarettes, and cigars. METHODS: Data from the 2021 National Youth Tobacco Survey (NYTS) were used to estimate the prevalence of current use of any tobacco product, e-cigarettes, cigarettes, and cigars by survey setting, sociodemographic characteristics, peer tobacco use, and other tobacco product use. Multivariable regression was used to test the impact of survey setting on current tobacco use. Tobacco access sources among current users were compared by survey setting. RESULTS: Among students who participated in the 2021 NYTS, 50.8% reported taking the survey on school campus and 49.2% at home/other place. The prevalence of current use of any tobacco product, e-cigarettes, cigarettes, and cigars was higher among students completing the survey on school campus than at home/other place. After adjusting for covariates, this association persisted only for current use of any tobacco product (adjusted odds ratio = 1.57; 95% confidence interval, 1.28-1.91) and e-cigarettes (adjusted odds ratio = 1.43; 95% confidence interval, 1.20-1.71). Current users reported similar sources of access to tobacco products, regardless of survey setting. DISCUSSION: The likelihood of youth reporting current use of any tobacco product and e-cigarettes differed by survey setting. Such differences could be due to lack of privacy at home, peer influence in school settings, and other unmeasured characteristics. Methodological changes were made due to COVID-19; caution is warranted in comparing results from the 2021 NYTS with those of previous or future NYTS conducted primarily on school campus.
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COVID-19 , Sistemas Eletrônicos de Liberação de Nicotina , Produtos do Tabaco , Tabagismo , Humanos , Adolescente , Estados Unidos/epidemiologia , Nicotiana , Fumar/epidemiologia , Uso de Tabaco/epidemiologiaRESUMO
PURPOSE: To retrospectively investigate the epicardial fat volume with multidetector computed tomography (MDCT) and other risk factors for the prevalence of three-vessel coronary lesion. MATERIALS AND METHODS: MDCT was performed on 424 subjects with or without three-vessel coronary lesion. Blood was tested for triglyceride, high-density lipoprotein (HDL), low-density lipoprotein (LDL), apolipoprotein A (ApoA), apolipoprotein B (ApoB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lipoprotein a, and fasting blood glucose. RESULTS: Among all the subjects, a significant (P < 0.05) negative linear correlation existed between age and ALT or ALT/AST. The epicardial fat had a significant (P < 0.05) negative linear correlation with HDL and Apo A but a positive correlation with age and ApoB/ApoA. The epicardial fat volume and the fasting blood glucose were significantly (P = 0.001) greater in the patients than in the control group, whereas HDL and Apo A were both significantly (P < 0.0001) smaller in the patients than in the control groups. A significant prediction value (P < 0.05) existed in age increase, male gender, epicardial fat increase, low HDL, high LDL, and elevated fasting blood glucose. CONCLUSION: Three-vessel coronary lesions are more prevalent in subjects with greater volume of epicardial fat and in male gender.
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Glicemia , Tomografia Computadorizada Multidetectores , Humanos , Masculino , Estudos Retrospectivos , Prevalência , Fatores de Risco , Apolipoproteínas B , Apolipoproteínas ARESUMO
Tobacco use* is the leading cause of preventable disease, disability, and death among adults in the United States (1). Youth use of tobacco products in any form is unsafe, and nearly all tobacco use begins during youth and young adulthood (2). The Food and Drug Administration (FDA) and CDC analyzed data from the 2022 National Youth Tobacco Survey (NYTS) to estimate current (past 30-day) use of eight tobacco products among U.S. middle (grades 6-8) and high school (grades 9-12) students. In 2022, approximately 11.3% of all students (representing 3.08 million persons) reported currently using any tobacco product, including 16.5% of high school and 4.5% of middle school students (2.51 million and 530,000 persons, respectively). Electronic cigarettes (e-cigarettes) were the most commonly used tobacco product among high school (14.1%; 2.14 million) and middle school (3.3%; 380,000) students. Approximately 3.7% of all students (representing 1 million persons) reported currently smoking any combustible tobacco product. Current use of any tobacco product was higher among certain population groups, including 13.5% of non-Hispanic American Indian or Alaska Native (AI/AN) students; 16.0% of students identifying as lesbian, gay, or bisexual (LGB); 16.6% of students identifying as transgender; 18.3% of students reporting severe psychological distress; 12.5% of students with low family affluence; and 27.2% of students with low academic achievement. Implementation of comprehensive evidence-based tobacco control strategies, combined with FDA regulation, is important for preventing and reducing youth tobacco product use (1,2).
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Sistemas Eletrônicos de Liberação de Nicotina , Produtos do Tabaco , Tabagismo , Adolescente , Adulto , Feminino , Humanos , Estados Unidos/epidemiologia , Adulto Jovem , Inquéritos Epidemiológicos , Uso de Tabaco/epidemiologia , Tabagismo/epidemiologia , EstudantesRESUMO
Purpose: To explore the risk factors of recurrence after second endovascular embolization of recurrent aneurysms and the characteristics of recurrent refractory aneurysms to help clinical decision-making. Materials and methods: Forty-nine patients with recurrent aneurysms who underwent repeated embolization were retrospectively enrolled and divided into the recurrent and non-recurrent group. The risk factors of recurrence, complications and follow-up results of repeated embolization, and characteristics of recurrent refractory aneurysms were analyzed. Results: Among the 49 patients with the second embolization, 5 were lost to follow-up, 9 recurred, and 35 did not. Univariate analysis showed that aneurysm size (P = 0.022), aneurysm classification (P = 0.014), and Raymond-Roy grade after the second embolization (P = 0.001) were statistically different between the two groups. Multivariate analysis demonstrated the Raymond-Roy grade as an independent risk factor for the recurrence of aneurysms after the second embolization (P = 0.042). The complication rate after the second embolization was 4%. There were five recurrent refractory aneurysms with an average aneurysm size of 23.17 ± 10.45 mm, including three giant aneurysms and two large aneurysms. To achieve complete or near-complete embolization of the recurrent refractory aneurysms, multiple treatment approaches were needed with multiple stents or flow diverting devices. Conclusion: Aneurysm occlusion status after the second embolization is an independent risk factor for the recurrence of intracranial aneurysms. Compared with near-complete occlusion, complete occlusion can significantly reduce the risk of recurrence after second embolization. In order to achieve complete or near-complete occlusion, recurrent refractory aneurysms need multiple treatments with the use of multiple stents or flow diverting devices.
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PURPOSE: The purpose of this study was to investigate the neuroprotective effect of donepezil against ß-amyloid25-35 (Aß25-35)-induced neurotoxicity and the possible mechanism. METHODS: PC12 cells were conventionally cultured. Serial concentrations of Aß25-35 and donepezil (0, 0.5, 1, 5, 10, 20 and 50 µmol/L) were added to the PC12 cells, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) staining was performed to detect the effects of these treatments on PC 12 viability. The PC 12 cells were pretreated with 1, 5, 10, 20 or 50 µmol/L donepezil two hours before 20 µmol/L Aß25-35 was added to pretreatment groups A, B, C, D and E. Normal control group I and the 20 µmol/L Aß25-35-treated group were selected. An MTT assay was used to detect PC12 cell viability, and the level of lactate dehydrogenase (LDH) was determined. PC12 cells were pretreated with 10 µmol/L GF109203X (a protein kinase C [PKC] antagonist) 30 min before 10 µmol/L donepezil was added to pretreatment group F, and normal control group II, the 10 µmol/L GF109203X-treated group and the 10 µmol/L donepezil-treated group were chosen. The expression of phosphorylation-PKC (P-PKC) and its major substrate phosphorylated myristoylated alanine-rich protein C kinase substrate (P-MARCKS) was measured by Western blotting. The effects of donepezil on the subcellular distribution of the PKCα and PKCε isoforms were detected by immunofluorescence staining. RESULTS: Treatment with Aß25-35 (5, 10, 20 or 50 µmol/L) for 24 h significantly (P < 0.05) decreased PC 12 cell viability in a dose-dependent manner. Compared with the PC12 cells in the control group, those in the 20 µmol/L Aß25-35-treated group exhibited lower viability but higher LDH release. Compared with the 20 µmol/L Aß25-35-treated group, pretreatment groups B, C, D and E exhibited significantly (P < 0.05) increased cell viability but significantly (P < 0.05) decreased LDH release. Western blotting demonstrated that compared with control, 10 µmol/L donepezil promoted PKC and MARCKS phosphorylation and that the expression of P-PKC and P-MARCKS in pretreatment group F was significantly (P < 0.05) lower than that in the donepezil-treated group. Immunofluorescence staining revealed that the PKCα and PKCε isoforms were located mainly in the cytoplasm of PC12 control cells, whereas donepezil increased the expression of the PKCα and PKCε isoforms in the membrane fraction. The Western blot results showed that donepezil altered the subcellular distribution of the PKCα and PKCε isoforms by decreasing their expression in the cytosolic fraction but increasing their expression in the membrane fraction. CONCLUSION: Donepezil can antagonize Aß25-350-induced neurotoxicity in PC 12 cells, and PKC activation may account for the neuroprotective effect of donepezil.
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Fármacos Neuroprotetores , Humanos , Animais , Ratos , Fármacos Neuroprotetores/farmacologia , Donepezila/farmacologia , Fragmentos de Peptídeos/toxicidade , Fragmentos de Peptídeos/metabolismo , Proteína Quinase C-alfa/farmacologia , ApoptoseRESUMO
Substantial evidence suggests that non-coding RNA plays a vital role in human cancer, especially long non-coding RNA (lncRNA) with a length greater than 200nt. Herein, we found a lncRNA facilitating human colorectal cancer (CRC) progression. DLGAP1-AS2 was significantly increased in CRC tissues and cell lines. Knockdown of DLGAP1-AS2 inhibited CRC cell proliferation, migration, invasion in vitro, and tumor growth in vivo. The subcellular localization of DLGAP1-AS2 was translocated from the cytoplasm of normal cells to the nucleus of CRC cells due to reduced levels of N6-methyladenosine (m6A) modification. Further, through the screening of a series of signal pathways, we found that Myc pathway was involved in the effect of DLGAP1-AS2. Silencing of DLGAP1-AS2 markedly reduced Myc mRNA and protein levels. Blockade of Myc effectively abolished the enhanced aggressive behaviors of CRC cells caused by DLGAP1-AS2 overexpression. Mechanistically, DLGAP1-AS2 directly bound CTCF, a well-known transcriptional repressor of Myc, resulting in reduced binding of CTCF on Myc promoter and activating Myc transcription. The second hairpin structure of DLGAP1-AS2 was critical for the interaction between DLGAP1-AS2 and CTCF in the nucleus. Taken together, our study reveals the oncogenic regulatory axis of DLGAP1-AS2/CTCF/Myc in CRC, implying a promising targeted therapy for clinical application.
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Neoplasias Colorretais , MicroRNAs , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , MicroRNAs/genética , Regulação Neoplásica da Expressão Gênica , Linhagem Celular Tumoral , Carcinogênese/genética , Neoplasias Colorretais/genética , Movimento Celular/genéticaRESUMO
Objectives: To explore the associations between posterior communicating artery (PComA) aneurysms and morphological characteristics of arteries upstream of and around the PComA bifurcation site. Methods: In this study, fifty-seven patients with PComA aneurysms and sixty-two control subjects without aneurysms were enrolled. The centerlines of the internal carotid artery (ICA) and important branches were generated for the measurement and analysis of morphological parameters, such as carotid siphon types, diameters of two fitting circles, and the angle formed by them (D1, D2, and Ï), length (L) and tortuosity (TL) of ICA segment between an ophthalmic artery and PComA bifurcations, bifurcation angle (θ), tortuosity (TICA and TPComA), and flow direction changes (θICA and θPComA) around the PComA bifurcation site. Results: No significant difference (p > 0.05) was found in the siphon types (p = 0.467) or L (p = 0.114). Significant differences (p < 0.05) were detected in D1 (p = 0.036), TL (p < 0.001), D2 (p = 0.004), Ï (p = 0.008), θ (p = 0.001), TICA (p < 0.001), TPComA (p = 0.012), θICA (p < 0.001), and θPComA (p < 0.001) between the two groups. TICA had the largest area under the curve (AUC) (0.843) in the receiver operating characteristic (ROC) analysis in diagnosing the probability of PComA aneurysms presence and was identified as the only potent morphological parameter (OR = 11.909) associated with PComA aneurysms presence. Conclusions: The high tortuosity of the ICA segment around the PComA bifurcation is associated with PComA aneurysm presence.
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THIS STUDY AIMED: to investigate the efficacy and long-term outcomes of endovascular embolization and surgical clipping for patients with posterior communicating artery unruptured aneurysms (PcomAs) concomitant with oculomotor nerve palsy (ONP). No significant (Pâ >â .05) difference existed in the age, gender, proportion of complete ONP, and size of eye fissure and pupil before treatment between 2 groups. After compared with before treatment, the eye fissure was widened significantly (Pâ <â .05) and the pupil narrowed significantly (Pâ <â .05), but no significant (Pâ >â .05) differences existed between the 2 groups. Complete ONP recovery was observed in 32 (80%) patients in the embolization group and 31 (77.5%) in the microsurgical group, partial ONP recovery occurred in 6 (15%) in the embolization group and 8 (20%) in the microsurgical group. The recovery rate was 95% in the embolization group and 97.5% in the microsurgical group, with no significant (Pâ >â .05) difference between 2 groups. The recovery rate of the ONP was significantly (Pâ <â .01) greater in the microsurgical group than that in the embolization group at follow-up of 1 month, 3 months, six and 12 months, respectively. At 18 months, the ONP recovery rate was not significantly different between 2 groups (95% vs 97.5%) Surgical clipping may have a faster effect on the recovery of oculomotor nerve palsy than endovascular embolization for patients with posterior communicating artery unruptured aneurysms complicated with oculomotor nerve palsy, but both approaches may result in a similar effect on the nerve recovery in the long run.Eighty patients treated with endovascular embolization or surgical clipping were retrospectively enrolled into the endovascular embolization group or surgical clipping and analyzed.
Assuntos
Embolização Terapêutica , Procedimentos Endovasculares , Aneurisma Intracraniano , Doenças do Nervo Oculomotor , Artérias , Embolização Terapêutica/métodos , Procedimentos Endovasculares/métodos , Humanos , Aneurisma Intracraniano/complicações , Aneurisma Intracraniano/cirurgia , Doenças do Nervo Oculomotor/complicações , Doenças do Nervo Oculomotor/cirurgia , Recuperação de Função Fisiológica/fisiologia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
INTRODUCTION: While risk factors for cigarette smoking among youth and young adults are well-documented, less is known about the correlates of initiation of other tobacco products. This study aims to provide estimates and correlates of initiation among U.S. youth and young adults. METHODS: Data on youth aged 12-17 (n = 10,072) and young adults aged 18-24 (N = 5,727) who provided information on cigarettes, electronic nicotine delivery systems (ENDS), cigars, pipe, hookah and smokeless tobacco use in Wave 1 (W1: 2013-2014)-Wave 4 (W4: 2016-2018) of the nationally-representative PATH Study were used to calculate ever use initiation and correlates of initiation by W4. RESULTS: Nearly 6 million youth and 2.5 million young adults used tobacco for the first time between W1-W4. Approximately one quarter of youth and young adult ENDS never users initiated ENDS between W1-W4 of the PATH Study. Among youth, use of other tobacco products, ever substance use, and high externalizing problems were associated with initiation of most products. Among young adults, use of other tobacco products and ever substance use were associated with initiation of most products. In both youth and young adults, Hispanics were more likely to initiate hookah use than their non-Hispanic White counterparts. While male sex was a risk factor for most tobacco product initiation across both age groups, it was not associated with hookah initiation. CONCLUSIONS: Cigarette and non-cigarette products shared many correlates of initiation, although there are noteworthy demographic differences. Findings can help tailor product specific interventions to reach populations at risk during preliminary stages of use.