多囊卵巢综合征患者口服炔雌醇环丙孕酮片致过敏反应

摘 要 目的：探讨临床药师在多囊卵巢综合征患者口服炔雌醇环丙孕酮片抗雄激素治疗中出现过敏反应的处理方法及药学监护。方法: 临床药师通过综合分析患者过敏史及用药史,结合患者用药时间和不良反应的发生时间,判断所用药物与过敏反应的相关性,并对其后续治疗替代药物提出用药建议。结果: 最终判定炔雌醇环丙孕酮片与此次不良反应的关联性评价为很可能,其中两种成分炔雌醇和醋酸环丙孕酮都不能排除为此次过敏反应的发生原因,建议选用屈螺酮炔雌醇片或含天然雌激素成分的口服避孕药进行后续替代治疗。结论:临床药师针对药物致过敏反应展开的病例分析及药学监护,有助于促进多囊卵巢综合征患者的个体化治疗,在保证用药安全,提高患者依从性方面发挥重要作用。     

柱前衍生HPLC法结合固相萃取测定血浆中卡托普利

目的:建立测定血浆中卡托普利浓度的方法,用于卡托普利人体药动学及相对生物利用度研究。方法:以对溴苯甲酸甲基溴为衍生化试剂,固相萃取法从生物样本中提取纯化衍生化产物,以反相高效液相色谱法测定衍生物含量而确定卡托普利血药浓度。结果:卡托普利血药浓度在10～1000ng·mL~(-1)范围内线性良好,相关系数为0.9987,测得平均回收率为98.65％,日内、日间RSD均小于10％。结论:本方法简便、准确、干扰小,适合用于卡托普利血药浓度监测及药动学研究。     

高效液相色谱法测定当归补血汤分煎液与合煎液中阿魏酸含量

目的；比较当归补血汤（当归，黄芪）分煎液与合煎液中阿魏酸含量。方法：采用HypersilC18，以甲醇-0.05%乙酸（45：55）为流动相，在324nm波长处测定。结果：分煎液阿魏液平均回收率为100.86%,RSD=2.33%。合煎液阿魏酸平均回收率为101.37%,RSD=1.52%。结论：合煎液中阿魏酸含量高于分煎液。     

A molecularly integrated grade for meningioma

BackgroundMeningiomas are the most common primary intracranial tumor in adults. Clinical care is currently guided by the World Health Organization (WHO) grade assigned to meningiomas, a 3-tiered grading system based on histopathology features, as well as extent of surgical resection. Clinical behavior, however, often fails to conform to the WHO grade. Additional prognostic information is needed to optimize patient management.MethodsWe evaluated whether chromosomal copy-number data improved prediction of time-to-recurrence for patients with meningioma who were treated with surgery, relative to the WHO schema. The models were developed using Cox proportional hazards, random survival forest, and gradient boosting in a discovery cohort of 527 meningioma patients and validated in 2 independent cohorts of 172 meningioma patients characterized by orthogonal genomic platforms.ResultsWe developed a 3-tiered grading scheme (Integrated Grades 1-3), which incorporated mitotic count and loss of chromosome 1p, 3p, 4, 6, 10, 14q, 18, 19, or CDKN2A. 32% of meningiomas reclassified to either a lower-risk or higher-risk Integrated Grade compared to their assigned WHO grade. The Integrated Grade more accurately identified meningioma patients at risk for recurrence, relative to the WHO grade, as determined by time-dependent area under the curve, average precision, and the Brier score.ConclusionWe propose a molecularly integrated grading scheme for meningiomas that significantly improves upon the current WHO grading system in prediction of progression-free survival. This framework can be broadly adopted by clinicians with relative ease using widely available genomic technologies and presents an advance in the care of meningioma patients.     

血清铁死亡标记物与绝经后女性认知障碍的关系

目的 研究血清铁死亡标记物与绝经后女性认知障碍的关系。方法 选取2019年8月至2021年12月就诊的148例女性,其中生育期女性22例,围绝经期女性11例,绝经后女性115例。按照蒙特利尔认知评估量表(Montreal cognitive assessment, MoCA)将绝经后女性分为认知障碍组(n=77)和无认知障碍组(n=38),比较两组血清铁死亡标记物有无差异,应用Logistic进行多因素回归分析绝经后女性认知障碍的相关因素。通过受试者工作特征曲线(Receiver operating characteristic curve, ROC)评估相关因素对绝经后女性认知障碍的诊断价值。结果 与生育期和围绝经期女性相比,绝经后女性MoCA评分明显较低,血清ACSL4、System Xc-、GPX4、GSH、ROS、LPO及MDA水平均明显升高(均P<0.05)。与无认知障碍组相比,认知障碍组绝经后女性受教育年限短、患高血压的比例高,且血清ACSL4、System Xc_-^{、GPX4、GSH、ROS、LPO及MDA水平明显}升高 (均P<0.05)。多因素Logistic回归分析显示教育年限和血清谷胱甘肽(glutathione, GSH)与认知障碍独立相关(P<0.05),ROC曲线分析显示两者联合对预测女性是否患认知障碍具有中度诊断价值(AUC: 0.764, P<0.05)。结论 绝经后女性血清铁死亡标志物ACSL4、System Xc_-^{、GPX4、GSH、ROS、LPO及MDA水平}明显升高,其中GSH与女性认知障碍发生独立相关,与受教育年限联合有望成为绝经后女性认知障碍早期诊断的潜在标志物。     

Prevalence and related factors of hyperuricaemia in Chinese children and adolescents: a pooled analysis of 11 population-based studies

Background and aimsHyperuricaemia can lead to gout and is associated with an increased risk of cardiometabolic disease. We aimed to investigate the prevalence of hyperuricaemia and its related factors in Chinese children and adolescents.MethodsWe pooled data from 11 population-based studies comprising 54,580 participants aged 3–19 years. The sex- and age-standardized prevalence of hyperuricaemia was estimated overall and by sex, age, weight status, geographic region and survey year.ResultsSerum uric acid (SUA) increased gradually from 3 to 11 years with no significant sex difference, and then increased dramatically during 11–15 years. The estimated overall prevalence of hyperuricaemia was 23.3% (26.6% in boys and 19.8% in girls, p < .001). The prevalence increased with growing age (3.7, 9.8, 15.8, 35.5 and 31.7% among children aged 3–5, 6–8, 9–11, 12–15 and 16–19 years, respectively, p for trend < .001) and with increasing weight status (18.2, 37.6, 50.6 and 64.5% among children with non-overweight, overweight, obesity and extreme obesity, respectively, p for trend < .001). The prevalence was higher in North than in South (24.2 vs. 19.7%, p < .001), and increased markedly from 16.7% during 2009–2015 to 24.8% during 2016–2019. In multivariable regression analyses, sex, age, obesity, region and survey year were independently associated with odds of hyperuricaemia.ConclusionsThe prevalence of hyperuricaemia in Chinese children and adolescents is unexpectedly high. The findings suggest an urgent need to implement effective interventions to reduce risk of hyperuricaemia in Chinese youths.

KEY MESSAGES

• Question: What is the prevalence of hyperuricaemia in Chinese children and adolescents?
• Findings: In this large pooled cross-sectional study comprising >50,000 children and adolescents aged 3–19 years, we found that the prevalence of hyperuricaemia was high in overall population and subgroups of sex, age, obesity, region and survey year.
• Meaning: Our findings indicate that hyperuricaemia is an important health problem in Chinese children and adolescents, and effective intervention strategies are needed to reduce its burden.

     

Exploring the Barriers and Motivators to Dietary Adherence among Caregivers of Children with Disorders of Amino Acid Metabolism (AAMDs): A Qualitative Study

Dietary intervention is generally accepted as the mainstay of treatment for patients with disorders of amino acid metabolism (AAMDs). However, dietary adherence to a low-protein diet is always reported as a common challenge among these patients. This study explored the perception of barriers and motivators to dietary adherence among caregivers of AAMD patients in Malaysia. Twenty caregivers of children with AAMDs receiving ongoing treatment at the genetic clinic participated in an online focus group discussion from November to December 2021. Findings showed a total of five interrelated main themes identified from focus group discussion (FGD) exploring parents’ experiences related to the management of their child’s daily diet. The barriers to dietary adherence were burden of dietary treatment, diet and dietary behavior, parenting challenges, limited knowledge related to dietary treatment, and challenges in healthcare system delivery. Key factors facilitating good dietary adherence include good knowledge of dietary treatment, parental coping strategies, social coping, and dietary behavior. In conclusion, despite the existence of several barriers to the implementation of dietary treatment, caregivers managed to use a wide range of coping strategies to overcome some, if not all, of the challenges. The important next step is to develop, in conjunction with multidisciplinary healthcare professionals, feasible implementation strategies that could address these barriers and at the same time improve the quality of life of caregivers.     

Numerical Investigation of the Influence of Ultimate-Strength Heterogeneity on Crack Propagation and Fracture Toughness in Welded Joints

The mechanical properties of dissimilar metal-welded joint materials are heterogeneous, which is an obstacle to the safety evaluation of key welded structures. The variation of stress–strain conditions at the crack tip caused by mismatch of material mechanical properties in dissimilar metal-welded joints is an important factor affecting crack propagation behavior. To understand the influence of uneven distribution of ultimate strength of the base metal and the welded metal on the crack propagation path, fracture toughness, as well as the mechanical field at the crack tip in the small-scale yield range, the user-defined field variable subroutine method is used to express continuous variation characteristics of welded joint ultimate strength in finite element software. In addition, the J-integral during crack propagation is calculated, and the effect of the ultimate strength on the J-integral and the stress field at the crack tip are analyzed. The results show that as the crack propagation direction is perpendicular to the direction of ultimate strength, the gradient of ultimate strength increases from |G_y|= 50 to |G_y|= 100 MPa/mm, the crack deflection angle increases by 0.018%, and the crack length increases by 1.46%. The fracture toughness of the material decreased slightly during crack propagation. Under the condition that the crack propagation direction is the same as the direction of ultimate strength, the crack propagation path is a straight line. As the gradient of ultimate strength increases from G_x = 50 to G_x = 100 MPa/mm, the crack propagation length decreases by 5.17%, and the slope of fracture toughness curve increases by 51.63%. On the contrary, as the crack propagates to the low ultimate strength side, the crack propagation resistance decreases, the ultimate strength gradient increases from G_x = −100 to G_x = −50 MPa/mm, and the slope of the fracture toughness curve decreases by 51.01%. It is suggested to consider the relationship between crack growth behavior and ultimate strength when designing and evaluating the structural integrity of cracks at the material interface of dissimilar metal-welded joints.     

Exosomes Derived from Glioma Cells under Hypoxia Promote Angiogenesis through Up-regulated Exosomal Connexin 43

Glioblastoma multiform (GBM) is a highly aggressive primary brain tumor. Exosomes derived from glioma cells under a hypoxic microenvironment play an important role in tumor biology including metastasis, angiogenesis and chemoresistance. However, the underlying mechanisms remain to be elucidated. In this study, we aimed to explore the role of connexin 43 on exosomal uptake and angiogenesis in glioma under hypoxia. U251 cells were exposed to 3% oxygen to achieve hypoxia, and the expression levels of HIF-1α and Cx43, involved in the colony formation and proliferation of cells were assessed. Exosomes were isolated by differential velocity centrifugation from U251 cells under normoxia and hypoxia (Nor-Exos and Hypo-Exos), respectively. Immunofluorescence staining, along with assays for CCK-8, tube formation and wound healing along with a transwell assay were conducted to profile exosomal uptake, proliferation, tube formation, migration and invasion of HUVECs, respectively. Our results revealed that Hypoxia significantly up-regulated the expression of HIF-1α in U251 cells as well as promoting proliferation and colony number. Hypoxia also increased the level of Cx43 in U251 cells and in the exosomes secreted. The uptake of Dio-stained Hypo-Exos by HUVECs was greater than that of Nor-Exos, and inhibition of Cx43 by ^37,43gap27 or lenti-Cx43-shRNA efficiently prevented the uptake of Hypo-Exos by recipient endothelial cells. In addition, the proliferation and total loops of HUVECs were remarkably increased at 24 h, 48 h, and 10 h after Hypo-Exos, respectively. Notably, ^37,43gap27, a specific Cx-mimetic peptide blocker of Cx37 and Cx43, efficiently alleviated Hypo-Exos-induced proliferation and tube formation by HUVECs. Finally, ^37,43gap27 also significantly attenuated Hypo-Exos-induced migration and invasion of HUVECs. These findings demonstrate that exosomal Cx43 contributes to glioma angiogenesis mediated by Hypo-Exos, and suggests that exosomal Cx43 might serve as a potential therapeutic target for glioblastoma.     

白塞综合征20例临床特征及心血管影像学分析

回顾性分析2018年1月—2020年8月首都医科大学附属北京安贞医院风湿免疫科治疗的白塞综合征患者20例的临床及影像学检查资料.20例患者中,男4例,女16例,平均年龄41.2岁,平均病程17.0年.超声、CT及MR检查发现心血管系统受累13例,主要表现为主动脉瓣脱垂并重度关闭不全,主动脉瘤、主动脉假性动脉瘤、主动脉溃...