惊厥患儿镇静后谵妄发生的危险因素及风险列线图预测模型的建立

目的调查惊厥患儿镇静后谵妄发生的危险因素，建立惊厥患儿镇静后谵妄风险列线图预测模型。方法前瞻性选取2020年8月—2022年1月在空军军医大学第二附属医院住院治疗的373例惊厥患儿作为研究对象，其中建模组245例，验证组128例。通过多因素logistic回归分析筛选患儿镇静后谵妄发生的独立预测因子，并建立列线图模型，分别采用校准曲线、受试者工作特征曲线和决策曲线分析对模型的准确度、区分度和临床应用价值进行评估。结果惊厥患儿镇静后谵妄发生率为22.3%（83/373）。多因素logistic回归分析显示，年龄>5岁是惊厥患儿镇静后谵妄的保护因素（OR=0.401，P<0.05），合并感染、入住儿童重症监护病房、应用苯二氮䓬类药物、惊厥持续状态史、谵妄发作史是危险因素（OR分别为3.020、3.126、5.219、2.623、3.119，均P<0.05）。列线图预测模型H-L偏差度检验显示出较好的拟合度（ χ2 =9.494，P=0.302）。内部、外部验证显示，校准曲线实际值与预测值间的平均绝对误差分别为0.030和0.018，受试者工作特征曲线下面积分别为0.777和0.775。决策曲线分析显示，当预测风险阈值>0.01时模型提供显著临床净收益。结论年龄、合并感染、入住儿童重症监护病房、应用苯二氮䓬类药物、惊厥持续状态史、谵妄发作史与惊厥患儿镇静后谵妄发生密切相关；根据这些因素建立的惊厥患儿镇静后谵妄风险列线图预测模型具有较高的准确度、区分度和临床应用价值。     

The cell cycle inhibitor P21 promotes the development of pulmonary fibrosis by suppressing lung alveolar regeneration

The cell cycle inhibitor P21 has been implicated in cell senescence and plays an important role in the injury–repair process following lung injury. Pulmonary fibrosis (PF) is a fibrotic lung disorder characterized by cell senescence in lung alveolar epithelial cells. In this study, we report that P21 expression was increased in alveolar epithelial type 2 cells (AEC2s) in a time-dependent manner following multiple bleomycin-induced PF. Repeated injury of AEC2s resulted in telomere shortening and triggered P21-dependent cell senescence. AEC2s with elevated expression of P21 lost their self-renewal and differentiation abilities. In particular, elevated P21 not only induced cell cycle arrest in AEC2s but also bound to P300 and β-catenin and inhibited AEC2 differentiation by disturbing the P300–β-catenin interaction. Meanwhile, senescent AEC2s triggered myofibroblast activation by releasing profibrotic cytokines. Knockdown of P21 restored AEC2-mediated lung alveolar regeneration in mice with chronic PF. The results of our study reveal a mechanism of P21-mediated lung regeneration failure during PF development, which suggests a potential strategy for the treatment of fibrotic lung diseases.     

Activating Connexin43 gap junctions primes adipose tissue for therapeutic intervention

Adipose tissue is a promising target for treating obesity and metabolic diseases. However, pharmacological agents usually fail to effectively engage adipocytes due to their extraordinarily large size and insufficient vascularization, especially in obese subjects. We have previously shown that during cold exposure, connexin43 (Cx43) gap junctions are induced and activated to connect neighboring adipocytes to share limited sympathetic neuronal input amongst multiple cells. We reason the same mechanism may be leveraged to improve the efficacy of various pharmacological agents that target adipose tissue. Using an adipose tissue-specific Cx43 overexpression mouse model, we demonstrate effectiveness in connecting adipocytes to augment metabolic efficacy of the β₃-adrenergic receptor agonist Mirabegron and FGF21. Additionally, combing those molecules with the Cx43 gap junction channel activator danegaptide shows a similar enhanced efficacy. In light of these findings, we propose a model in which connecting adipocytes via Cx43 gap junction channels primes adipose tissue to pharmacological agents designed to engage it. Thus, Cx43 gap junction activators hold great potential for combination with additional agents targeting adipose tissue.     

Clinical Utility of Genomic Assay in Node-Positive Early-Stage Breast Cancer

Breast cancer (BC) is the most common malignancy among women in Canada. Adjuvant treatment in early BC can reduce the risk of BC recurrence. Historically, the decision for adjuvant chemotherapy for early BC was made only based on clinical and tumour characteristics. In recent years, there has been an effort toward developing genomic assays as a predictive and prognostic tool to improve precision in estimating disease recurrence, sensitivity to systemic treatment and ultimately with clinical utility for guidance regarding adjuvant systemic treatment(s). There are various commercial genomic tests available for early-stage ER+/HER-2 negative BC. This paper will review the Oncotype DX 21-gene Recurrence Score (RS), MammaPrint, EndoPredict, Prosigna^®, and Breast Cancer Index (BCI) genomic assays. We will also focus on these genomic assays’ clinical application and utility in node-positive early-stage BC based on the most recent evidence and guidance recommendations.     

新生儿疾病筛查人群中CYP21基因P30L和V281L突变携带者频率的研究

目的研究新生儿疾病筛查人群中CYP21基因P30L和V281L突变杂合子的频率分布。方法58份新生儿干血滤纸片测定17-OHP,同时提取新生儿脐带血DNA,应用PCR扩增和限制性内切酶分析P30L和V281L两种与21-OHD相关的CYP21基因突变,计算杂合子频率。结果在116个等位基因中有1个鉴定出P30L突变,未鉴定出V281L突变。本研究人群中P30L的携带者频率为0.9%,V281L的携带者频率为0。结论本研究新生儿筛查正常人群中可检出CYP21基因突变携带者,对人群中CYP21基因突变携带者的研究有助于对漏检21-OHD的基因突变分析。     

青阳参中C21甾体成分研究

该文用硅胶,ODS,MCI柱色谱和半制备型HPLC等方法对青阳参的氯仿萃取中含有的C₂₁甾体类成分进行了系统的分离纯化研究,并结合波谱数据对该类成分进行了结构确认。从青阳参氯仿萃取物分离到11个C₂₁甾体类化合物,分别为青阳参苷乙（1）,告达亭-3-O-β-D-加拿大麻吡喃糖基-（1→4）-β-D-夹竹桃吡喃糖基-（1→4）-β-D-加拿大麻吡喃糖基-（1→4）-β-D-加拿大麻吡喃糖苷（2）,告达亭-3-O-β-D-夹竹桃吡喃糖基-（1→4）-β-D-夹竹桃吡喃糖基-（1→4）-β-D-加拿大麻吡喃糖基-（1→4）-β-D-加拿大麻吡喃糖苷（3）,告达亭-3-O-β-D-夹竹桃吡喃糖基-（1→4）-β-D-毛地黄毒吡喃糖基-（1→4）-β-D-加拿大麻吡喃糖苷（4）,青阳参苷O（5）,加加明-3-O-β-D-夹竹桃吡喃糖基-（1→4）-β-D-加拿大麻吡喃糖基-（1→4）-β-D-加拿大麻吡喃糖苷（6）,sinomarinoside B（7）,mucronatosides C（8）,wallicoside J（9）,stephanoside H（10）,青阳参苷元-3-O-β-D-夹竹桃吡喃糖基-（1→4）-β-D-加拿大麻吡喃糖基-（1→4）-β-D-毛地黄毒吡喃糖苷（11）。除化合物 1,4和5外其他成分均为首次从该植物中分离得到的C₂₁甾体类化合物。     

FGF21在PCOS患者血清中的表达及意义

目的:评价多囊卵巢综合征(PCOS)患者血清中成纤维细胞因子21(FGF21)的表达,初步探讨FGF21在PCOS发病中的作用。方法:研究对象分为PCOS组和正常对照组。PCOS组分为肥胖患者和非肥胖患者。分别用酶联免疫法(ELISA)测定血清FGF21水平;采取磁酶免法测定黄体生成素(LH)、睾酮(T);应用化学发光法检测空腹血糖(FBG)、空腹胰岛素(Ins)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)水平。结果:PCOS组FGF21表达明显高于对照组(P<0.01),并且与体重指数(BMI)、Ins(r=0.423,P<0.01;r=0.341,P<0.05)成正相关;在PCOS组中,肥胖患者血清中的FGF21水平高于非肥胖患者(P<0.05),与IR、LH(r=0.440,P=0.046;r=0.44,P=0.044)成正相关。结论:PCOS患者血清中FGF21水平明显高于对照组,在PCOS组中肥胖患者血清中FGF21水平明显高于非肥胖患者。FGF21有望成为PCOS治疗中的新突破。     

Isolated Intracardiac Echogenic Focus on Routine Ultrasound: Implications for Practice

Ultrasound is widely used as a screening tool for fetal anomalies. An intracardiac echogenic focus (ICEF) is associated with fetal aneuploidy, particularly trisomy 21, when found with other minor abnormalities known as soft markers. However, when found in isolation, intracardiac echogenic foci are morphologic variations with little or no pathologic significance for the fetus. Ambiguity about the significance of ICEF and other soft markers and the lack of preparation prior to ultrasound can result in unnecessary worry for women and their partners. A variety of tools exist that providers can use to help pregnant women and their partners make informed decisions about ultrasound and fetal screening.     

Prenatal Diagnosis and Treatment of Steroid 21-Hydroxylase Deficiency

Steroid 21-hydroxylase deficiency (21-OHD) accounts for 90–95% of congenital adrenal hyperplasia (CAH) cases. It is classified into three distinct clinical phenotypes: the salt-wasting (SW), simple virilizing (SV) and nonclassical forms (NC). As girls with the SW and SV forms of 21-OHD are exposed to high systemic levels of adrenal androgens during fetal life, they show genital ambiguity. To ameliorate the degree of genital virilization, prenatal dexamethasone treatment has been performed for more than two decades, although mainly in the USA and Europe. This treatment has proven to be effective in preventing or reducing genital virilization. Some data also show that prenatal diagnosis and treatment are safe for the mother and fetus. However, prenatal treatment is still controversial for the following reasons. First, the risk of having an affected female fetus is only one in eight when both parents are known carriers of the autosomal recessive trait. Therefore, seven of eight fetuses will receive dexamethasone unnecessarily, and this raises ethical questions. Furthermore, maternal side effects such as excessive weight gain and hypertension have been observed. Finally, the long-term safety and outcome for dexamethasone-exposed children have not been established. In Japan, prenatal diagnosis and treatment has rarely been reported because of these reasons. Therefore, we must be cautious, and this treatment should be carried out in special centers with the approval of their ethical committees, that are capable of performing chorionic villus sampling (CVS) and subsequently determining the karyotype and genotype of 21-OHD.