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背景 心血管疾病(CVD)是常见病和多发病,患病率和死亡率呈快速上升趋势。动脉粥样硬化(AS是缺血性CVD的病理基础,研究表明心外膜脂肪组织(EAT)通过分泌外泌体(EXO)和生物活性物质促进AS进展,但其作用机制仍需进一步研究。目的 通过生物信息学方法挖掘冠状动脉粥样硬化性心脏病(CAD)患者EAT中的关键基因,探讨免疫细胞浸润情况,联合CAD患者EXO间差异表达基因(DEGs)推测EAT来源EXO间DEGs并进行验证,从细胞及分子水平上探讨EAT在CAD疾病过程中的作用机制。方法 从基因表达综合数据库(GEO)中下载关于EAT的数据集GSE64554、GSE120774,根据临床信息将EAT的测序数据分为CAD组和健康对照组,使用R语言及相关软件包进行生物信息学分析。首先使用R语言筛选CAD组与健康对照组EAT间DEGs,并进行GO富集分析和KEGG通路富集分析,构建蛋白质-蛋白质相互作用(PPI)网络,评估所选基因的生物学功能及可能参与其调控的转录因子。构建GSE64554数据集中EAT的加权基因共表达网络(WGCNA),获取同CAD表型相关的基因模块,将所获EAT间DEGs与模... 相似文献
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Wang JG Liu L Zagato L Xie J Fagard R Jin K Wang J Li Y Bianchi G Staessen JA Liu L 《Journal of molecular medicine (Berlin, Germany)》2004,82(10):715-722
We recently found in a white population that the genes encoding angiotensin-converting enzyme (ACE, I/D polymorphism), -adducin (Gly460Trp), and aldosterone synthase (–344C/T) jointly influence renal function. We therefore investigated in a Chinese population the associations between the serum concentrations of creatinine and uric acid and these three genetic polymorphisms. We genotyped 471 ethnic Han Chinese subjects from 125 nuclear families recruited in northern China via random population sampling (75%) and at specialized hypertension clinics (25%). We performed population-based and family-based association analyses using generalized estimating equations (GEE) and quantitative transmission disequilibrium test (QTDT), respectively, while controlling for covariables. The participants were 39.7 years old and included 235 women (49.9%). The blood pressure measured at the subjects homes averaged 126/80 mmHg. Mean values were 71 µmol/l for serum creatinine, 111 ml min–1 1.73 m–2 for calculated creatinine clearance, and 236 µmol/l for serum uric acid. With adjustment for covariables, GEE analyses of single genes demonstrated that serum uric acid, but not serum creatinine, was positively associated with the ACE D allele. Serum uric acid concentrations were 15.8 µmol/l (95% confidence interval 3.3–28.2) and 25.7 µmol/l (11.1–40.2) higher in DD homozygotes than in ID and II subjects, respectively. Further GEE analyses of the three genes combined showed that the association between serum uric acid and the ACE polymorphism was confined to carriers of the -adducin Gly and/or aldosterone synthase C alleles. Sensitivity analyses in parents and offspring separately as well as QTDT analyses were confirmatory. Among 114 informative offspring carrying the -adducin Gly allele serum uric acid was significantly and positively associated with the transmission of the ACE D allele (=20.7 µmol/l). In conclusion, the present study extends our previous findings on the combined effects of the three candidate genes and supports the concept that these genetic polymorphisms jointly influence renal function. 相似文献
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《Autoimmunity reviews》2023,22(2):103264
Idiopathic inflammatory myopathies (IIM) are a group of different conditions typically affecting striate muscle, lung, joints, skin and gastrointestinal tract. Treatment typically relies on glucocorticoids and synthetic immunosuppressants, but the occurrence of refractory, difficult to treat, manifestations, may require more aggressive treatment, borrowed from other autoimmune diseases, including biologic disease modifying drugs (bDMARDs). In this regard, we conducted a systemic literature review in order to depict the current evidence about the use of bDMARDs in IIM. A total of 78 papers, published during the last 21 years, were retrieved. The majority of patients was treated with TNF-α inhibitors, whose effectiveness was assessed particularly in recalcitrant striate muscle, skin and joints involvement. Rituximab, whose evidence is supported by a large number of real-life studies and trials, seems to be an excellent option in case of ILD and anti-synthetase syndrome, while Tocilizumab, despite not meeting primary and secondary endpoints in a recently published clinical trial, proved its effectiveness in rapidly progressing ILD. Similarly, Abatacept, studied in a phase IIb clinical trial with conflicting evidence, was reported to be effective in some case reports of refractory dermatomyositis. Less data exist for anti-IL1 and anti-IL23 agents, which were employed particularly for inclusion body myositis and severe skin disease, respectively. This study provides an organ-focused assessment of bDMARDs in IIM, which display encouraging results in the treatment of refractory subsets of disease. 相似文献
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《Autoimmunity reviews》2023,22(3):103270
BackgroundIt is now accepted that immune tolerance disorders caused by inadequate Treg cell function or number are important factors in the development and progression of rheumatic diseases. There is increasing evidence that ld IL-2 treatment increases the proportion of Treg cells in patients' peripheral blood, but this conclusion is still controversial. Here, we performed a meta-analysis of reports documenting the proportion of Treg cells and the rate of adverse events in patients with rheumatic disease before and after the administration of ld IL-2 to better understand its effect and safety on Treg cells in the field of rheumatic diseases.MethodsWe systematically searched PubMed, Embase, Scopus, Cochrane Library, and Web of science databases up to 15th November 2022 and identified studies that reported the proportion of peripheral blood Treg cells before and after ld IL-2 treatment in patients with rheumatic disease. Random-effects model was used to perform a meta-analysis of Treg cell proportions before and after ld IL-2 administration, and a meta-regression analysis was performed to explore heterogeneity. Inconsistency was evaluated using the I-squared index (I2), and publication bias was assessed by examining funnel plot asymmetry using the Egger tests.ResultsEighteen studies involving 1608 patients were included in the meta-analysis. The proportion of Treg cells in peripheral blood of these patients increased significantly after receiving ld IL-2 treatment [1.07 (95% CI 0.86,1.27), p < 0.001, I2 = 67.3%]. Next, Meta-regression was performed for 5 variables including publish year, disease type, trail type and dosage and duration of the medication. The results suggest that these variables do not lead to high heterogeneity. (p = 0.698, 0.267, 0.502, 0.843, 0.560, respectively). And finally, statistical analysis showed no difference in adverse reactions between ld IL-2 group and control group in treatment [1.06 (95% CI 0.86,1.31), p = 0.586, I2 = 53.8%], which is unreliable because the data is so small.ConclusionsLd IL-2 does increase the proportion of peripheral blood Treg cells in patients with rheumatism, and single and cumulative doses must be considered when using ld IL-2. In addition, more studies on the safety of ld IL-2 are urgently needed. 相似文献
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ObjectiveThe frontal basal interhemispheric approach (FBIA) is preferable for resection of craniopharyngioma (CP), achieving desirable total resection rates in early reports of lesions located in the suprasellar region to the third ventricle. For tumours that have created a larger obstruction of the tuberculum sellae and planum sphenoidale, aggressive resection in the intrasellar region and medial wall of the cavernous sinus is not feasible compared to improving tumour visualization by drilling the tuberculum sellae and planum sphenoidale. In a report of drilling the sellar tuberculum and sphenoid planum, drilling allowed the direct visualization of tumours invading the intrasellar region and medial wall of the cavernous sinus. Reconstructing the opening of the sellar-sphenoid cavity is achieved by microsuturing a piece of the pericranium/dura around the dural edge of the defective dura of the open sphenoid sinus and sellar cavity to prevent cerebrospinal fluid (CSF) leakage.Patients and methodsThe FBIA with drilling of the tuberculum sellae and planum sphenoidale was performed to remove the tumours that invaded the intrasellar region and cavernous sinus in 55 patients from January 2014 to October 2019 at our institution. The pre- and postoperative pituitary hormone levels and vision were evaluated as effective standards after surgery and compared using paired t-tests. The different rates of CSF leakage between the packing and microsuture groups were compared by χ2 test, p < 0.05.ResultsIn all patients with a mean 37-month follow-up (range, 3–2 months), 43 (78.2%) patients returned to their normal life or school independently, 7 (12.7%) patients were able to perform normal activities with minor complaints or effort, and 4 (7.3%) patients could care for themselves or only required occasional assistance. One (1.8%) death occurred, attributed to CSF leak-related meningitis at 5 months after surgery. Postoperative CSF leakage occurred in eight (19.0%) of 42 patients with packed bone wax or pieces of muscle to the sphenoid sinus. Of 13 patients with a piece of the periosteum/dura microsutured around the defective dura of the sellar region and open sphenoid sinus, one (7.7%) of 13 patients experienced CSF leakage in the perioperative period. With statistical analysis, there was a potential risk for postoperative CSF leakage in the bone wax and muscle piece in the open sphenoid sinus, whereas microsuture manoeuvres were effective for avoiding the risk of postoperative CSF leakage (χ2 = 8.865, p < 0.005). The microsutures closed the open sphenoid sinus such that it was water-tight. Postoperative visual acuity and the visual field were not affected by the increased intrasellar exposure or the open sphenoid sinus achieved by drilling the tuberculum sellae and planum sphenoidale.ConclusionTuberculum sellae/planum sphenoidale drilling via FBIA is feasible to enhance the direct visualization of CP resection, which expands the intrasellar region with a direct resection of recurrent tumours in the sellar cavity and adhering to the medial wall of the cavernous sinus. The potential risk of a CSF leakage seemed to be mitigated when using water-tight microsutures on a piece of the pericranium/dura around the edge of the defective dura in the sellar region and the open sphenoid sinus cavity. 相似文献
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ObjectiveTo investigate whether the dance therapy was more beneficial than non-dance therapy on cognitive and mood symptoms in patients with Parkinson's disease (PD).MethodsMEDLINE, CINAHL, Embase and the Cochrane Central Register of Controlled Trials were searched from inception to December 11, 2018. Risk of bias for the included trials was assessed using criteria in the Cochrane Handbook for Systematic Reviews of Interventions.ResultsSeven randomized controlled trials were identified on cognitive and mood symptoms in patients with PD. There were significant differences in favor of dance in executive function (WMD = 1.17, 95% CI:0.39 to 1.95, P = 0.003; I2 = 0%, P = 0.45), but not in outcomes of global cognitive function, depression and apathy.ConclusionsDance therapy is beneficial in improving executive function for adults with PD. However, there are no positive effects were founded on global cognitive function, depression and apathy for PD. 相似文献
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《European journal of surgical oncology》2021,47(5):1140-1144
BackgroundAchieving negative margins for melanoma in situ, lentigo maligna type can be challenging, particularly on cosmetically sensitive areas.ObjectiveTo assess the utility of intraoperative frozen section margin assessment using a teledermatopathology system in the treatment of head and neck lentigo maligna.Methods and materialsOver a 6 year period, 96 patients with lentigo maligna had surgical excisions. The margins were assessed intraoperatively with frozen sections prepared in the manner used in Mohs surgery. The surgeon guided the frozen section slides around the margin while a dermatopathologist assessed the margin remotely.ResultsIn 2/96 (2.1%) cases, the safety margin was positive (frozen sections were false negative). In 1 further case (1%) there was a recurrence of the melanoma 13 months following the excision.ConclusionThe described method is effective in treating melanoma in situ, lentigo maligna type with clearance rates similar to previous studies for Mohs surgery. 相似文献
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