steroids

类固醇
  • 文章类型: Journal Article
    炎性肌纤维母细胞瘤(IMT)是一种罕见的间质肿瘤,由伴有炎症细胞的肌纤维母细胞梭形细胞定义,淋巴细胞和嗜酸性粒细胞。其症状学取决于受累部位,并倾向于在临床和放射学上模仿恶性肿瘤。头部和颈部区域占所有IMT的5%。这里,我们报告了一个35岁女性的病例,没有病史,他的开口限制为8毫米,持续三年,并在智齿拔除后六个月发生。她还经历了最近发生的左眼下垂和斜视会聚。在检查中,病人的体温为37℃,左下巴和眶下区域的下摆,没有任何其他异常。实验室检查未发现生物学炎症综合征或横纹肌溶解症。传染病调查都是阴性的,以及免疫学测试,特别是对于抗AChR和抗MuSK抗体呈阴性。在面部计算机断层扫描(CT)扫描中,我们注意到左下颌骨上升分支的活跃改组,同侧翼状肌和左颞膜组织增厚。皮质类固醇治疗后0.7mg/kg/j,我们获得了病人张口的改善,因此,在局部麻醉下对病变进行了活检,揭示IMT。患者继续进行皮质类固醇治疗,逐渐逐渐变细,导致张口限制和下垂的临床明显改善。
    结论:炎性肌纤维母细胞瘤(IMT)是一种具有挑战性的疾病。鉴于该疾病的可变临床和放射学表现,知道它是最重要的,迅速识别,以便迅速做出诊断。适应治疗应立即开始,以防止可能危及生命的结果。
    An inflammatory myofibroblastic tumour (IMT) is a rare neoplasm of mesenchymal origin, defined by myofibroblastic spindle cells accompanied by inflammatory cells, lymphocytes and eosinophils. Its symptomatology depends on the involved site and tends to mimic a malignant tumour clinically and radiologically. The head and neck region accounts for 5% of all IMTs. Here, we report a case of a 35-year-old woman, with no medical history, who presented with a mouth-opening limitation of 8 mm evolving for three years and occurring six months after of a wisdom tooth extraction. She also experienced a recent occurrence of left eye ptosis and a converging strabismus. On examination, the patient had a body temperature at 37°C, with hypoesthaesia of the left chin and infraorbital area, without any other abnormality. Laboratory examinations did not reveal a biological inflammatory syndrome or rhabdomyolysis. The infectious investigations were all negative, as well as the immunological tests, in particular negative for anti-AChR and anti-MuSK antibodies. On the facial computed tomography (CT) scan, we noted an active reshuffle in the left mandible ascending branch with a thickening of the ipsilateral pterygoid muscles and the left temporal meningeal tissue. After corticosteroid therapy 0.7 mg/kg/j, we obtained an improvement in the patient\'s mouth-opening, thus a biopsy of the lesion was performed under local anaesthesia, revealing IMT. The patient continued the corticosteroids therapy with a progressive tapering resulting in a marked clinical improvement of the mouth-opening limitation and her ptosis.
    CONCLUSIONS: An inflammatory myofibroblastic tumour (IMT) is a challenging disease.Given the variable clinical and radiological presentation of the disease, it is of paramount importance to know it, to be swiftly recognised so diagnosis can be promptly made.The adapted treatment should be immediately started to prevent possible life-threatening outcomes.
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  • 文章类型: Journal Article
    生物催化类固醇羟基化过程的实施在制药工业中起着至关重要的作用,这是由于羟基化类固醇衍生物的药物作用过多以及它们在药物审批过程中的关键作用。细胞色素P450单加氧酶(CYP450)通常构成催化这些反应的关键酶,但是通常会带来缺点,例如催化速率差以及从NAD(P)H到活性位点的电子转移对其他氧化还原蛋白的依赖性。最近,通过为大肠杆菌细胞配备自给自足的单组分CYP450BM3的高活性变体以及促进细胞类固醇摄取的疏水性外膜蛋白,克服了这些瓶颈。BM3变体KSA14m和外膜孔AlkL的组合可以使睾丸激素的羟化速率异常高,达到45UgCDW-1,用于静息(即,活着但不生长的)细胞。然而,比活性的快速损失严重损害了最终产品的滴度和整体时空产率。在这项研究中,几种稳定策略在酶上进行了评估-,cell-,和反应水平。然而,既不改变生物催化剂的配置,也不改变培养基,表达系统,或诱导剂浓度导致相当大的改善。这证明了迄今为止使用的遗传构建体pETM11-ksa14m-alkL,M9中等,和静止细胞状态是最佳选择,可以在生物转化之前实现相对有效的活动以及快速的生长。总之,我们报告了几种方法不能稳定高睾酮羟化率,为研究人员解决类似的CYP450稳定性问题提供重要指导。在等效设置中与更稳定的天然类固醇羟基化CYP106A2和CYP154C5的比较进一步强调了所研究的基于CYP450BM3的全细胞生物催化剂的高潜力。巨大且不断发展的酶工程策略库提供了稳定高活性生物催化剂的有希望的选择。
    The implementation of biocatalytic steroid hydroxylation processes plays a crucial role in the pharmaceutical industry due to a plethora of medicative effects of hydroxylated steroid derivatives and their crucial role in drug approval processes. Cytochrome P450 monooxygenases (CYP450s) typically constitute the key enzymes catalyzing these reactions, but commonly entail drawbacks such as poor catalytic rates and the dependency on additional redox proteins for electron transfer from NAD(P)H to the active site. Recently, these bottlenecks were overcome by equipping Escherichia coli cells with highly active variants of the self-sufficient single-component CYP450 BM3 together with hydrophobic outer membrane proteins facilitating cellular steroid uptake. The combination of the BM3 variant KSA14m and the outer membrane pore AlkL enabled exceptionally high testosterone hydroxylation rates of up to 45 U gCDW-1 for resting (i.e., living but non-growing) cells. However, a rapid loss of specific activity heavily compromised final product titers and overall space-time yields. In this study, several stabilization strategies were evaluated on enzyme-, cell-, and reaction level. However, neither changes in biocatalyst configuration nor variation of cultivation media, expression systems, or inducer concentrations led to considerable improvement. This qualified the so-far used genetic construct pETM11-ksa14m-alkL, M9 medium, and the resting-cell state as the best options enabling comparatively efficient activity along with fast growth prior to biotransformation. In summary, we report several approaches not enabling a stabilization of the high testosterone hydroxylation rates, providing vital guidance for researchers tackling similar CYP450 stability issues. A comparison with more stable natively steroid-hydroxylating CYP106A2 and CYP154C5 in equivalent setups further highlighted the high potential of the investigated CYP450 BM3-based whole-cell biocatalysts. The immense and continuously developing repertoire of enzyme engineering strategies provides promising options to stabilize the highly active biocatalysts.
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  • 文章类型: Journal Article
    确定疗效,有效性,和透视或超声引导下的尾硬膜外类固醇注射(ESI)有或没有导管放置治疗慢性腰背(CLBP)的安全性,神经根疼痛,和/或慢性手术后背痛(CPSBP)。
    系统评价。
    患有CLBP的成年人≥18岁,神经根疼痛,或CPSBP≥3个月。
    透视或超声引导的尾部ESI,无论是否使用导管,包括硬膜外神经成形术。
    Sham,安慰剂程序,积极的标准护理治疗,或者没有。
    主要结果是疼痛减轻≥50%的个体比例。次要结果包括功能改善,镇痛药的使用,随后的脊柱手术,医疗保健利用,意味着疼痛的改善。报告的不良事件也被编目。
    四位审稿人在2022年1月2日之前在PubMed独立评估出版物,OvidMEDLINE,还有Scopus.使用推荐标准对证据质量进行评估,评估,发展,和评估(等级)框架。
    筛选的364条记录中,23份出版物符合纳入标准。主要结局的成功率只能从一项研究中推断出来。另一项研究使用了包括疼痛和功能结果的复合改善量表。这两项研究报告的成功率在三个月时从40%到58%不等,六个月时25%-67%,一年的58%-61%。次要结果的数据有限;然而,通过Oswestry残疾指数(ODI)的平均改善来衡量的功能改善率范围为2%至55%。
    有中等质量的证据表明,使用留置导管两天的尾部ESI是治疗与椎间盘突出症和神经根疼痛相关的疼痛和功能障碍的有效方法,六,和12个月。有低质量的证据支持其他尾管ESI技术治疗中央腰椎管狭窄伴神经源性跛行的疼痛和功能障碍的有效性。盘源性CLBP,和CLBP无椎间盘突出或神经根炎。
    UNASSIGNED: Determine the efficacy, effectiveness, and safety of fluoroscopically- or ultrasound-guided caudal epidural steroid injections (ESIs) with or without catheter placement for the treatment of chronic low back (CLBP), radicular pain, and/or chronic post-surgical back pain (CPSBP).
    UNASSIGNED: Systematic review.
    UNASSIGNED: Adults ≥18 years with CLBP, radicular pain, or CPSBP ≥3 months.
    UNASSIGNED: Fluoroscopically- or ultrasound-guided caudal ESI with or without a catheter including epidural neuroplasty.
    UNASSIGNED: Sham, placebo procedure, active standard care treatment, or none.
    UNASSIGNED: The primary outcome was the proportion of individuals with reduction of pain by ​≥ ​50%. Secondary outcomes included functional improvement, analgesic use, subsequent spinal surgery, healthcare utilization, and mean improvement in pain. Reported adverse events were also cataloged.
    UNASSIGNED: Four reviewers independently assessed publications before January 2, 2022 in PubMed, Ovid MEDLINE, and Scopus. Quality of evidence was evaluated using the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) framework.
    UNASSIGNED: Of 364 records screened, 23 publications met inclusion criteria. The success rates for the primary outcome could only be extrapolated from one study. Another study used a composite improvement scale that included pain and functional outcomes. The reported success rates in these two studies ranged from 40 to 58% at three months, 25%-67% at six months, and 58%-61% at one year. Data on secondary outcomes were limited; however, rates of functional improvement as measured by mean improvement in Oswestry Disability Index (ODI) ranged from 2% to 55%.
    UNASSIGNED: There is moderate-quality evidence that caudal ESIs using an in-dwelling catheter for two days is an effective treatment for pain and dysfunction associated with disc herniation with radicular pain and for CPSBP at three, six, and 12 months. There is low-quality evidence supporting the effectiveness of other caudal ESI techniques for pain and dysfunction associated with central lumbar spinal stenosis with neurogenic claudication, discogenic CLBP, and CLBP without disc herniation or radiculitis.
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  • 文章类型: Journal Article
    超声引导下屈肌支持带内皮质类固醇注射与腕管内类固醇注射的疗效比较,用于治疗老年腕管综合征(CTS)。
    在这个前景中,双盲,随机试验,将患有CTS的老年患者1:1分为两个治疗组.受试者和评估者在整个试验过程中对组分配保持盲态。所有患者接受40毫克曲安奈德(1毫升)加1毫升2%利多卡因,在屈肌支持带中开窗(第1组)或在屈肌支持带和正中神经之间的腕管内注射(第2组)。指示患者在治疗后使用腕带夹板两周。症状严重程度,握把,电诊断指标,在基线和6周后测量超声特征.主要结果是正中神经远端运动和感觉潜伏期,次要结果是波士顿腕管问卷(BCTQ)得分,视觉模拟量表(VAS)疼痛评分,和正中神经入口横截面积(CSA)。
    在接受筛查的92个人中,50名符合条件的参与者被随机分配,所有患者均完成研究并纳入分析.接受屈肌内支持带注射的患者在其总BCTQ评分方面表现出显著更大的改善(p=0.023)。VAS评分(p=0.026),和进口CSA(p=0.004),而电诊断指标和握力量表在组间没有差异。
    屈肌支持带内皮质类固醇注射液可以为患有CTS的老年患者提供更好的功能恢复和症状减轻,与腕管内注射皮质类固醇相比。
    UNASSIGNED: The efficacy of ultrasonography-guided intra-flexor retinaculum corticosteroid injection is compared to within-carpal tunnel steroid injection, for the treatment of elderly patients with carpal tunnel syndrome (CTS).
    UNASSIGNED: In this prospective, double-blind, randomized trial, the elderly patients with CTS are allocated 1:1 into the two treatment groups. Subjects and assessors remained blinded to group allocation throughout the trial. All patients received 40 ​mg triamcinolone (1 ​mL) plus 1 ​mL of 2% lidocaine, either fenestrated in the flexor retinaculum (group 1) or injected within the carpal tunnel between the flexor retinaculum and median nerve (group 2). Patients were instructed to use a wrist splint for two weeks post-treatment. Symptom severity, grip, electrodiagnostic indices, and ultrasonographic features were measured at baseline and 6-weeks thereafter. The primary outcomes were median nerve distal motor and sensory latencies, and those secondary outcomes were Boston Carpal Tunnel Questionnaire (BCTQ) scores, visual analog scale (VAS) pain scores, and the median nerve inlet cross-sectional area (CSA).
    UNASSIGNED: Of 92 individuals screened, 50 eligible participants were randomized, all of whom completed the study and were included in the analysis. Patients receiving the intra-flexor retinaculum injection demonstrated significantly greater improvements in their total BCTQ score (p ​= ​0.023), VAS score (p ​= ​0.026), and inlet CSA (p ​= ​0.004), while the electrodiagnostic indices and the grip scale did not differ between groups.
    UNASSIGNED: The intra-flexor retinaculum corticosteroid injection can provide better functional recovery and symptom reduction for elderly patients with CTS, compared to the within-carpal tunnel corticosteroid injection.
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  • 文章类型: Journal Article
    为了确定中性粒细胞与淋巴细胞比率(NLR)作为POC标记物的诊断潜力,以区分结核性和非结核性CAP,并在北阿坎德邦的三级护理中心确定局限性,印度。
    从普通医学诊所招募了225名出现呼吸道不适的患者并进行了调查。在发病时注意到NLR,并与最终诊断相关。
    两组的NLR没有统计学上的显著差异。曲线下面积(AUC)在鉴别结核性和非结核性CAP方面的准确率为49.1%,并且注意到先前类固醇暴露对NLR的异常影响是一种局限性。
    我们的结果与先前研究的差异值得对NLR的显著限制的文献进行回顾。NLR受儿茶酚胺的影响,这使得外源性类固醇暴露患者的标记不可靠。在以前的研究中没有注意到这一点。我们认为在大流行中滥用类固醇会混淆我们的发现。我们建议在未来的研究中考虑这一限制,以便可以确定NLR的真正效用。
    UNASSIGNED: To determine the diagnostic potential of neutrophil-to-lymphocyte ratio (NLR) as a POC marker to discriminate tuberculous from non-tuberculous CAP and identify limitations if any at a tertiary care centre in Uttarakhand, India.
    UNASSIGNED: 225 patients presenting with respiratory complaints were recruited from the General Medicine clinics and investigated. NLR was noted at onset and correlated with final diagnosis.
    UNASSIGNED: NLR from both groups did not exhibit a statistically significant difference. The area under curve (AUC) exhibited an accuracy of 49.1% in differentiating tuberculous from non-tubercular CAP, and an anomalous effect of prior steroid exposure on NLR was noted as a limitation.
    UNASSIGNED: The disparity of our results from previous studies warranted a review of literature which rendered a significant limitation of NLR. The NLR is affected by catecholamines, which makes the marker unreliable in patients with exogenous steroid exposure. This was not noted in the previous studies. We presume indiscriminate steroid usage in the pandemic confounded our findings. We propose that this limitation be accounted for in future studies so that NLR\'s true utility may be identified.
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  • 文章类型: Journal Article
    先前关于全氟烷基和多氟烷基物质(PFAS)与自闭症谱系障碍(ASD)之间关联的研究得出的结果不一致,潜在的机制仍然未知。在这项研究中,我们对396例新生儿脐带血标本中的13例PFAS进行了量化,并在4岁时对这些患儿进行了随访,以评估ASD相关症状.我们的发现揭示了某些PFAS和ASD相关症状之间的关联,全氟壬酸(PFNA)加倍,全氟癸酸(PFDA),和全氟十一烷酸(PFUnDA)浓度与语言相关症状中分别增加1.79、1.62和1.45个单位相关,而PFDA与感觉刺激得分较高相关。在6:2氯化多氟化醚磺酸盐(Cl-PFAES)和8:2Cl-PFAES与ASD相关症状的关联中观察到非线性关联。采用加权分位数和(WQS)回归,我们观察到多种PFAS对ASD相关症状的所有领域的显着混合效应,PFNA成为最重要的贡献者。假设因果关系,我们发现,长链PFAS(PFUnDA和PFDoDA)暴露对感觉刺激的估计效应中有39-40%是由雄烯二酮介导的.这项研究提供了有关产前PFAS混合物暴露和ASD相关症状的新流行病学数据。
    Previous studies regarding the associations between perfluoroalkyl and polyfluoroalkyl substances (PFAS) and autism spectrum disorder (ASD) have yielded inconsistent results, with the underlying mechanisms remaining unknown. In this study, we quantified 13 PFAS in cord serum samples from 396 neonates and followed the children at age 4 to assess ASD-related symptoms. Our findings revealed associations between certain PFAS and ASD-related symptoms, with a doubling of perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA) concentrations associated with respective increases of 1.79, 1.62, and 1.45 units in language-related symptoms and PFDA exhibiting an association with higher score of sensory stimuli. Nonlinear associations were observed in the associations of 6:2 chlorinated polyfluorinated ether sulfonate (Cl-PFAES) and 8:2 Cl-PFAES with ASD-related symptoms. Employing weighted quantile sum (WQS) regression, we observed significant mixture effects of multiple PFAS on all domains of ASD-related symptoms, with PFNA emerging as the most substantial contributor. Assuming causality, we found that 39-40% of the estimated effect of long-chain PFAS (PFUnDA and PFDoDA) exposure on sensory stimuli was mediated by androstenedione. This study provides novel epidemiological data about prenatal PFAS mixture exposure and ASD-related symptoms.
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  • 文章类型: Journal Article
    燕麦稻草,一种AvenasativaL.的残留物,以其丰富的纤维素而闻名,半纤维素,和木质素。然而,在生物炼制概念的框架内,其作为亲脂性化合物来源的潜力仍未开发。在这项研究中,我们对两种不同燕麦品种的燕麦秸秆的丙酮提取物中存在的亲脂性化合物的含量和化学组成进行了广泛的调查,即,Karen和Isaura.此外,我们研究了春季和冬季种植的燕麦秸秆样品中含量和成分的季节性变化。提取的亲脂性化合物主要由高分子量酯(26.0-38.1%)组成,类固醇(16.6-24.0%),正脂肪醇(10.9-20.7%),正脂肪酸(10.9-16.0%),和正醛(10.7-15.8%),正构烷烃含量较低(1.1-3.0%),酰基甘油酯(2.3-3.8%),植醇和植酯(0.6-2.9%),β-二酮(0.1-2.5%),三萜类化合物(0.9-1.2%),生育酚和生育酚酯(0.2-0.7%),2-羟基脂肪酸(0.1-0.2%),和正烷基间苯二酚(0.1%)。值得注意的是,这些不同类别的化合物显示出其含量的差异,这取决于燕麦品种和特定的种植季节。特别感兴趣的是凯伦品种,存在大量的高分子量酯,游离脂肪酸,和酰基甘油,尤其是在冬季种植的时候。这些发现强调了燕麦秸秆作为生物炼制背景下脂质提取的宝贵资源的潜力,并强调了选择合适的品种和季节以获得最佳脂质产量的重要性。
    Oat straw, a residue of Avena sativa L., is recognized for its abundance in cellulose, hemicelluloses, and lignin. However, its potential as a source of lipophilic compounds within the framework of a biorefinery concept still remains unexplored. In this study, we conducted an extensive investigation into the content and chemical composition of the lipophilic compounds present in acetone extracts from oat straws of two distinct oat varieties, namely, Karen and Isaura. Furthermore, we examined their seasonal variability in content and composition in straw samples from oats planted in both spring and winter seasons. The extracted lipophilic compounds were predominantly composed of high molecular weight esters (26.0-38.1%), steroids (16.6-24.0%), n-fatty alcohols (10.9-20.7%), n-fatty acids (10.9-16.0%), and n-aldehydes (10.7-15.8%), with lower amounts of n-alkanes (1.1-3.0%), acylglycerides (2.3-3.8%), phytol and phytyl esters (0.6-2.9%), β-diketones (0.1-2.5%), triterpenoids (0.9-1.2%), tocopherols and tocopheryl esters (0.2-0.7%), 2-hydroxy fatty acids (0.1-0.2%), and n-alkylresorcinols (0.1%). Notably, these different classes of compounds exhibited variations in their contents depending on the oat variety and the specific planting season. Of particular interest was the Karen variety, which presented significant amounts of high molecular weight esters, free fatty acids, and acylglycerols, especially when it was cultivated during the winter season. These findings underline the potential of oat straw as a valuable resource for lipid extraction within a biorefinery context and emphasize the importance of selecting the appropriate variety and season for optimal lipid yield.
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  • 文章类型: Case Reports
    深部夹层血肿(DDH)是一种轻微创伤导致广泛血肿形成的疾病。如果不及时治疗,这会导致明显的皮肤坏死。因此,准确诊断后的早期治疗至关重要.然而,该疾病的复杂性可能需要将其与软组织感染区分开来。一名58岁的患有2019年严重冠状病毒病(COVID-19)肺炎的男子在接受静脉-静脉体外膜氧合(VV-ECMO)时,右上肢出现了紫癜和水疱等皮肤并发症。我们最初怀疑由VV-ECMO套管引起的软组织感染或静脉灌注缺损;然而,这些条件没有观察到。做了探索性切口后,我们诊断为DDH患者,并进行了血肿清除和植皮。DDH的最初症状包括红斑,肿胀,和痛苦。区分DDH和软组织感染很重要,尤其是坏死性筋膜炎,这是一个更紧迫的条件。因为手术切口对于DDH的诊断和治疗是必要的,我们毫不犹豫地进行探索性切口以防止皮肤坏死,有助于早期愈合。
    Deep dissecting hematoma (DDH) is a disease in which minor trauma leads to the formation of an extensive hematoma. If left untreated, this can result in significant skin necrosis. Therefore, early treatment following a precise diagnosis is essential. However, the complexity of the disease may require differentiating it from soft tissue infections. A 58-year-old man with severe coronavirus disease 2019 (COVID-19) pneumonia developed skin complications such as purpura and blisters on his right upper extremity while undergoing veno-venous extracorporeal membrane oxygenation (VV-ECMO). We initially suspected a soft tissue infection or venous perfusion defect caused by the VV-ECMO cannula; however, these conditions were not observed. After making an exploratory incision, we diagnosed the patient with DDH and performed hematoma removal and skin grafting. The initial symptoms of DDH include erythema, swelling, and pain. It is important to differentiate DDH from soft tissue infections, especially necrotizing fasciitis, which is a more urgent condition. Because a surgical incision is necessary for the diagnosis and treatment of DDH, we do not hesitate to perform an exploratory incision to prevent skin necrosis, thereby contributing to early healing.
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  • 文章类型: Journal Article
    背景:急性肝衰竭(ALF)可能是威尔逊病(WD)的第一个也是最引人注目的表现。由于WD引起的ALF(WD-ALF)难以与肝病的其他原因区分开,并且是肝移植的明确指征。关于这种情况的具体和支持性医学治疗没有明确的建议。
    目的:严格评估WD-ALF患者的诊断和治疗管理,以提高其天然肝脏的生存率。
    方法:回顾性分析2018年至2023年在两个儿科肝脏单元中患有WD-ALF的患者。
    结果:在研究期间,16名儿童(9名男性)被诊断为WD,其中2名患有ALF。第一种是用低剂量的D-青霉胺和锌加类固醇的非常规组合成功治疗,没有肝移植就存活了下来.第二个,完全用支持疗法治疗,需要肝移植手术来克服ALF。
    结论:小剂量D-青霉胺和锌加类固醇对1例WD-ALF患者的成功治疗可能为这种情况的治疗提供新的视角,目前只能接受肝移植治疗。
    BACKGROUND: Acute liver failure (ALF) may be the first and most dramatic presentation of Wilson\'s disease (WD). ALF due to WD (WD-ALF) is difficult to distinguish from other causes of liver disease and is a clear indication for liver transplantation. There is no firm recommendation on specific and supportive medical treatment for this condition.
    OBJECTIVE: To critically evaluate the diagnostic and therapeutic management of WD-ALF patients in order to improve their survival with native liver.
    METHODS: A retrospective analysis of patients with WD-ALF was conducted in two pediatric liver units from 2018 to 2023.
    RESULTS: During the study period, 16 children (9 males) received a diagnosis of WD and 2 of them presented with ALF. The first was successfully treated with an unconventional combination of low doses of D-penicillamine and zinc plus steroids, and survived without liver transplant. The second, exclusively treated with supportive therapy, needed a hepatotransplant to overcome ALF.
    CONCLUSIONS: Successful treatment of 1 WD-ALF patient with low-dose D-penicillamine and zinc plus steroids may provide new perspectives for management of this condition, which is currently only treated with liver transplantation.
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  • 文章类型: Journal Article
    背景:气相色谱同位素比质谱(GC-C-IRMS)长期以来一直在常规实验室中用于确定尿液中合成代谢类固醇的δ13C值,区分,例如,运动兴奋剂控制中的内源性和合成睾酮(T)。直到现在,液相色谱(LC-IRMS)尚未使用。LC-IRMS设置不允许流动相中的有机溶剂或改性剂用于δ13C测定。可以在加热到高温的水中分析中到非极性分析物,例如类固醇(HT,高达200°C),因为在200°C下具有与环境温度下的80/20甲醇/水相似的极性。在这项工作中,我们开发了一种尿液中类固醇的方法,将LC-IRMS的应用扩展到复杂基质中的非极性分析物。
    结果:一种能够确定四种类固醇的δ13C值的HT-LC-IRMS方法(即,睾酮(T),5α-雄甾烷-3α,17β-二醇(ααβ),5β-雄甾烷-3α,开发并验证了尿液中的17β-二醇(βαβ)和孕三醇(PT)。精度范围从0.23‰(ααβ和βαβ)到0.49‰(T),检测限设置为10ngmL-1(T,ααβ+βαβ)。验证数据和用HT-LC-IRMS和GC-C-IRMS分析的真实尿液样品的比较表明HT-LC-IRMS和GC-C-IRMS之间的相当性能。
    结论:HT-LC-IRMS可用于测定合成代谢类固醇的δ13C值,将HT-LC和LC-IRMS的适用性扩展到常规实验室实践中在复杂基质中确定的非极性物质。
    BACKGROUND: Gas Chromatography Isotope Ratio Mass Spectrometry (GC-C-IRMS) has long been used in routine laboratories to determine the δ13C values of anabolic steroids in urine, differentiating between, e.g., endogenous and synthetic testosterone (T) in sports doping control. Until now, liquid chromatography (LC-IRMS) has not been used. The LC-IRMS setup doesn\'t allow organic solvents or modifiers in the mobile phase for δ13C determinations. Mid-to non-polar analytes such as steroids can be analysed in water heated to High Temperatures (HT, up to 200 °C) because at 200 °C has a similar polarity as 80/20 methanol/water at ambient temperature. In this work, we developed a method for steroids in urine, extending the application of the LC-IRMS to non-polar analytes in complex matrices.
    RESULTS: An HT-LC-IRMS method capable of determining the δ13C values of four steroids (i.e., testosterone (T), 5α-androstane-3α,17β-diol (ααβ), 5β-androstane-3α,17β-diol (βαβ) and pregnanetriol (PT)) in urine was developed and validated. Accuracy ranged from 0.23 ‰ (ααβ and βαβ) to 0.49 ‰ (T), and the detection limit was set at 10 ng mL-1 (T, ααβ+βαβ). The validation data and a comparison of authentic urine samples analysed with HT-LC-IRMS and GC-C-IRMS indicated a comparable performance between HT-LC-IRMS and GC-C-IRMS.
    CONCLUSIONS: HT-LC-IRMS can be used to determine δ13C values of anabolic steroids, extending the applicability of both HT-LC and LC-IRMS to non-polar substances determined in a complex matrix in routine laboratory practice.
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