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S. Kim M.J. Graham R.G. Lee L. Yang S. Kim V. Subramanian J.D. Layne L. Cai R.E. Temel D. Shih A.J. Lusis J.A. Berliner S. Lee 《Nutrition, metabolism, and cardiovascular diseases : NMCD》2019,29(3):306-315
Background and aims
Heparin-binding EGF-like growth factor (HB-EGF) is a representative EGF family member that interacts with EGFR under diverse stress environment. Previously, we reported that the HB-EGF-targeting using antisense oligonucleotide (ASO) effectively suppressed an aortic aneurysm in the vessel wall and circulatory lipid levels. In this study, we further examined the effects of the HB-EGF ASO administration on the development of hyperlipidemia-associated atherosclerosis using an atherogenic mouse model.Methods and results
The male and female LDLR deficient mice under Western diet containing 21% fat and 0.2% cholesterol content were cotreated with control and HB-EGF ASOs for 12 weeks. We observed that the HB-EGF ASO administration effectively downregulated circulatory VLDL- and LDL-associated lipid levels in circulation; concordantly, the HB-EGF targeting effectively suppressed the development of atherosclerosis in the aorta. An EGFR blocker BIBX1382 administration suppressed the hepatic TG secretion rate, suggesting a positive role of the HB-EGF signaling for the hepatic VLDL production. We newly observed that there was a significant improvement of the insulin sensitivity by the HB-EGF ASO administration in a mouse model under the Western diet as demonstrated by the improvement of the glucose and insulin tolerances.Conclusion
The HB-EGF ASO administration effectively downregulated circulatory lipid levels by suppressing hepatic VLDL production rate, which leads to effective protection against atherosclerosis in the vascular wall. 相似文献104.
Farah Ladak Jerry T. Dang Noah J. Switzer Valentin Mocanu Daniel W. Birch Shahzeer Karmali 《Surgery for obesity and related diseases》2019,15(3):431-440
BackgroundComplications arising from laparoscopic Roux-en-Y gastric bypass (LRYGB) and laparoscopic sleeve gastrectomy (LSG) are not insignificant and can necessitate additional invasive interventions or reoperations.ObjectivesIn this study, we identify early complications that result in nonoperative and operative interventions after LSG and LRYGB, the timeframe within which to expect them, and factors that influence the likelihood of their occurrence.SettingMulti-institutional database from across North America.MethodsData for this study were obtained from Metabolic and Bariatric Accreditation and Quality Improvement Program participant use files for 2015 and 2016. Statistical analysis was performed using STATA 15. Univariate analysis using Χ2 for categoric data and independent t test for continuous data was performed to determine between group differences. Multivariable logistic regression analysis was used to identify predictors of operative and nonoperative reinterventions.ResultsIn 2015 and 2016, 243,747 underwent LRYGB or LSG, of which 3013 (1.24%) required a second operative procedure and 1536 (0.63%) required an invasive but nonoperative intervention. Complications occurred in 5.48% of LRYGB patients and 2.28% of LSG patients, the most common of which was bleeding. LSG was associated with far fewer nonoperative and operative interventions (.85% versus 2.2%, respectively) than LRYGB (.67% versus 2.5%). Renal insufficiency, including dialysis dependency, was an important predictor of reoperations among bariatric surgery patients. This was also true of nonoperative interventions; however, history of pulmonary embolism, and use of therapeutic anticoagulation were marginally stronger predictors.ConclusionsIn a representative, multinational sample, operative and nonoperative interventions were half as likely among LSG patients compared with LRYGB; however, overall rates still remained low. These findings, in conjunction with new efficacy data demonstrating comparable long-term weight loss between LRYGB and LSG, provide further support for the safety, effectiveness, and cost efficiency of LSG. 相似文献
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Noemie Luong-Gardiol Imran Siddiqui Irene Pizzitola Beena Jeevan-Raj Mélanie Charmoy Yun Huang Anja Irmisch Sara Curtet Georgi S. Angelov Maxime Danilo Mélanie Juilland Beat Bornhauser Margot Thome Oliver Hantschel Yves Chalandon Gianni Cazzaniga Jean-Pierre Bourquin Joerg Huelsken Werner Held 《Cancer cell》2019,35(4):649-663.e10
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目的:探讨加味甘草干姜汤联合维生素B12治疗复发性口腔溃疡(ROU)的临床效果。方法:选取2016年8月至2018年8月重庆市人民医院收治的ROU患者124例作为研究对象,随机分成观察组和对照组,每组62例。对照组口服维生素B12治疗,观察组在此基础上内服加味甘草干姜汤治疗,疗程均为14 d。比较2组疗效及安全性。结果:观察组总有效率达96.8%(60/62),显著高于对照组85.5%(53/62),差异有统计学意义(P<0.05)。与治疗前比较,2组治疗后疼痛指数、溃疡面积和平均溃疡期均显著改善,差异有统计学意义(P<0.05),外周血CD3+、CD4+水平和CD4+/CD8+比值及唾液中链球菌、韦荣菌数量均显著上升,差异有统计学意义(P<0.05),外周血CD8+水平均显著下降,差异有统计学意义(P<0.05);且观察组比对照组对以上指标的改善更显著,差异有统计学意义(P<0.05)。2组均未见明显不良反应。随访6个月,观察组复发率为11.3%(7/62),较对照组的25.8%(16/62)显著降低,差异有统计学意义(P<0.05)。结论:加味甘草干姜汤联合维生素B12治疗ROU的整体疗效确切,可能与其显著纠正外周血T淋巴细胞亚群免疫失衡、维持口腔微环境稳态有关。 相似文献
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Visar Vela Darius Juskevicius Magdalena M. Gerlach Peter Meyer Anne Graber Gieri Cathomas Stefan Dirnhofer Alexandar Tzankov 《Hematological oncology》2020,38(3):284-292
The majority of ocular adnexal (OA) lymphomas (OAL) are extranodal marginal zone lymphomas (MZL). First high throughput sequencing (HTS) studies on OA-MZL showed inconsistent results and the distribution of mutations in reactive lymphoid lesions of this anatomic region has not yet been sufficiently addressed. We characterized OAL and lymphoid lesions of the OA by targeted HTS. The study included 34 OA-MZL, 11 chronic conjunctivitis, five mature small cell B-cell lymphomas spreading to the OA, five diseases with increase of IgG4+ plasma cells, three Burkitt lymphomas (BL), three diffuse large B-cell lymphomas (DLBCL), three mantle cell lymphomas, three idiopathic orbital inflammations/orbital pseudo tumors (PT), and three OA lymphoid hyperplasia. All cases were negative for Chlamydia. The mutational number was highest in BL and lowest in PT. The most commonly (and exclusively) mutated gene in OA-MZL was TNFAIP3 (10 of 34 cases). Altogether, 20 out of 34 patients harbored mutually exclusive mutations of either TNFAIP3, BCL10, MYD88, ATM, BRAF, or NFKBIE, or nonexclusive mutations of IRF8, TNFRSF14, KLHL6, and TBL1XR1, all encoding for NK-κB pathway compounds or regulators. Thirteen patients (38%) had, to a great part, mutually exclusive mutations of chromatin modifier-encoding genes: KMT2D, CREBBP, BCL7A, DNMT3A, EP300, or HIST1H1E. Only four patients harbored co-occurring mutations of genes encoding for NK-κB compounds and chromatin modifiers. Finally, PTEN, KMT2D, PRDM1, and HIST1H2BK mutations were observable in reactive lymphoid lesions too, while such instances were devoid of NF-κB compound mutations and/or mutations of acetyltransferase-encoding genes. In conclusion, 80% of OA-MZL display mutations of either NK-κB compounds or chromatin modifiers. Lymphoid lesions of the OA bearing NF-κB compound mutations and/or mutations of acetyltransferase-encoding genes highly likely represent lymphomas. 相似文献