The mammary gland is a sensitive pubertal target in CD-1 and C57Bl/6 mice following perinatal perfluorooctanoic acid (PFOA) exposure

Perfluorooctanoic acid (PFOA) is a developmental toxicant in mice, with varied strain outcomes depending on dose and period of exposure. The impact of PFOA on female mouse pubertal development at low doses (≤1 mg/kg) has yet to be determined. Therefore, female offspring from CD-1 and C57Bl/6 dams exposed to PFOA, creating serum concentrations similar to humans, were examined for pubertal onset, including mammary gland development. Pups demonstrated a shorter PFOA elimination half-life than that reported for adult mice. Prenatal exposure to PFOA caused significant mammary developmental delays in female offspring in both strains. Delays started during puberty and persisted into young adulthood; severity was dose-dependent. Also an evaluation of female serum hormone levels and pubertal timing onset revealed no effects of PFOA compared to controls in either strain. These data suggest that the mammary gland is more sensitive to early low level PFOA exposures compared to other pubertal endpoints, regardless of strain.     

高效液相色谱法测定血中伊立替康及活性代谢物SN-38浓度

目的：建立高效液相色谱法同时测定结直肠癌患者血中的伊立替康（CPT-11）及其活性代谢物7-乙基-10-羟基喜树碱（SN-38）的浓度,并对我院基因型指导给药方案进行评价。方法：以2μg·mL-110-羟基喜树碱作为内标,先用100μL 10%高氯酸沉淀蛋白,再用50μL 10%高氯酸酸化血浆。采用Agilent ZORBAX Eclipse C8色谱柱（4.6 mm×150 mm,5μm）对CPT-11和SN-38进行分离;以0.05 mol·L-1的磷酸二氢钠-乙腈-三乙胺（75∶25∶0.1,v∶v,磷酸调pH 3.0）为流动相;荧光检测波长：激发波长380 nm,发射波长550 nm。结果：人血浆中CPT-11和SN-38线性范围均为3~1000 ng·mL-1,定量下限为3 ng·mL-1;准确度分别是98.5%和100.0%;回收率分别是83.8%和84.3%。结论：本方法可靠、简便、快速,可为伊立替康个体化给药提供参考。     

老年人β2肾上腺素能受体单倍型／多态性与支气管哮喘关系的研究

目的研究老年人群β2肾上腺素能受体（β2AR）基因的单核苷酸单倍型／多态性与支气管哮喘的关系。方法用直接DNA测序法测定了70例哮喘患者和112例健康体检者β2AR5个位点（-47，-20，46，79，252）的单核苷酸多态性（SNPs），并确定单倍型。结果哮喘组及对照组5个位点的基因型分布频率的差异无显著性（P〉0．05）；所有测定对象中发现3个常见的纯合型单倍型，分别为TTACG、TTGCA和CCGGG；46与79位所组成的单倍型与其他3个位点的之间存在着明显的连锁不平衡。结论β2AR单倍型／多态性不是老年人哮喘发病的遗传决定因素，β2AR基因5个位点之间的连锁不平衡性可能影响哮喘的临床表现。     

Progressive implantable cardioverter-defibrillator therapies for ventricular tachycardia: The efficacy and safety of multiple bursts,ramps, and low-energy shocks

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术前CT直方图分析预测食管鳞状细胞癌EGFR表达

目的 观察CT直方图参数与食管鳞状细胞癌（ESCC）表皮生长因子受体（EGFR）表达状态的相关性,评价其预测ESCC的EGFR表达状态的效能。方法 回顾性分析109例经术后病理证实ESCC患者术前胸部CT,获取其直方图参数。记录EGFR检测结果,将EGFR表达（－/+）归为低表达,EGFR表达（++/+++）归为高表达。比较EGFR高、低表达ESCC间直方图参数的差异。针对差异有统计学意义的参数行受试者工作特征（ROC）曲线分析,评价其预测EGFR表达状态的效能,分析CT直方图参数与EGFR表达的相关性。结果 109例ESCC中,40例EGFR低表达,69例高表达;其中22例EGFR表达（－）,18例（+）,27例（++）,42例（+++）。EGFR高、低表达肿瘤的平扫CT灰度平均值（Mean）、最大值（Max）、第10、25、50、75、90百分位数（10^th、25^th、50^th、75^th、90^th percentile）、峰度（kurtosis）及增强前后参数差值ΔMean、Δ50^th、Δ75^th、Δ90^th percentile差异均有统计学意义（P均<0.05）。平扫CT肿瘤灰度75^th和90^th percentile预测ESCC的EGFR表达状态的诊断效能最优,曲线下面积（AUC）均为0.69。平扫CT Mean、Max、Min、5^th、10^th、25^th、50^th、75^th、90^th percentile、kurtosis、ΔMean及Δ5^th、Δ10^th、Δ25^th、Δ50^th、Δ75^th percentile与EGFR表达呈弱至低度相关（|r|=0.20~0.37,P均<0.05）,增强CT直方图参数与EGFR表达无明显相关。结论 平扫CT直方图参数可用于术前预测ESCC的EGFR表达状态,尤以75^th和90^th percentile效能较佳。     

Biomarkers in the prognostic evaluation of ischemic stroke: Is there benefit in the measurements of TREM-1 and TREM-2 in the acute phase?

Background and purposeTriggering receptors expressed on myeloid cells 1 and 2 (TREM-1 and TREM-2) are cell surface receptors important for modulation of microglia immune response. In this study, we evaluate serum levels of TREM-1 and TREM-2 as potential biomarkers in acute ischemic stroke (AIS).Material and methodsProspective cohort study of 50 patients with AIS admitted at our hospital. Serum TREM-1 and TREM-2 was evaluated within 24 h of the acute event and on the third and fifth days after the stroke. Neurological stroke severity and global disability were determined with the National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) at the same three times and at the time of hospital discharge.ResultsTREM-1 and TREM-2 levels were elevated in stroke. TREM-1, but not TREM-2, exhibited correlations with NIHSS and mRS within 24 h (NIHSS and TREM-1: r_S = 0.31, p = 0.029; mRS and TREM-1: r_S = 0.32, p = 0.023). The serum level of TREM-1 within 24 h correlated with the neurological outcomes at hospital discharge (NIHSS and TREM-1: p = 0.021; mRS and TREM-1: p = 0.049). The serum concentrations of TREM-1 protein within 24 h after stroke was significantly higher in patients with poor outcome (mRS > 2) at hospital discharge (p = 0.021). After Exact Logistic Regression, large segmental stroke (O.R. = 4.14; 95CI = 1.07–16.09; p = 0.040) and initial sTREM levels (O.R. = 1.02; 95CI 1.00–1.04; p = 0.045) remained independent prognostic factors for AIS poor outcome (mRS > 2).ConclusionIn our study, TREM-1 and TREM-2 were significantly increased in AIS. Early elevation of TREM-1 correlated with stroke severity and it was an independent prognostic factor for stroke outcome.     

Clinical and Radiological Characteristics Associated with Respiratory Failure in Unilateral Lateral Medullary Infarction

BackgroundThe prognosis for unilateral lateral medullary infarction (ULMI) is generally good but may be aggravated by respiratory failure with fatal outcome. Respiratory failure has been reported in patients with severe bulbar dysfunction and large rostral medullary lesions, but its associated factors have not been systematically studied. We aimed to assess clinical and radiological characteristics associated with respiratory failure in patients with pure acute ULMI.Materials and MethodsSeventy-one patients (median age 55 years, 59 males) with MRI-confirmed acute pure ULMI were studied retrospectively. Clinical characteristics were assessed and bulbar symptoms were scored using a scale developed for this study. MRI lesions were classified into 4 groups based on their vertical extent (localized/extensive) and the involvement of the open and/or closed medulla. Clinical characteristics, bulbar scores and MRI lesion characteristics were compared between patients with and without respiratory failure.ResultsRespiratory failure occurred in 8(11%) patients. All patients with respiratory failure were male (p = 0.336), had extensive lesions involving the open medulla (p = 0.061), progression of bulbar symptoms (p=0.002) and aspiration pneumonia (p < 0.001). Peak bulbar score (OR, 7.9 [95% CI, 2.3–160.0]; p < 0.001) and older age (OR, 1.2 [95%CI, 1.0-1.6]; p=0.006) were independently associated with respiratory failure.ConclusionsExtensive damage involving the open/rostral medulla, clinically presenting with severe bulbar dysfunction, in conjunction with factors such as aspiration pneumonia and older age appears to be crucial for the development of respiratory failure in pure ULMI. Further prospective studies are needed to identify other potential risk factors, pathophysiology, and effective preventive measures for respiratory failure in these patients.     

Paclitaxel-induced stress granules increase LINE-1 mRNA stability to promote drug resistance in breast cancer cells

Abnormal expression of long interspersed element-1 (LINE-1) has been implicated in drug resistance, while our previous study showed that chemotherapy drug paclitaxel (PTX) increased LINE-1 level with unknown mechanism. Bioinformatics analysis suggested the regulation of LINE-1 mRNA by drug-induced stress granules (SGs). This study aimed to explore whether and how SGs are involved in drug-induced LINE-1 increase and thereby promotes drug resistance of triple negative breast cancer (TNBC) cells. We demonstrated that SGs increased LINE-1 expression by recruiting and stabilizing LINE-1 mRNA under drug stress, thereby adapting TNBC cells to chemotherapy drugs. Moreover, LINE-1 inhibitor efavirenz (EFV) could inhibit drug-induced SG to destabilize LINE-1. Our study provides the first evidence of the regulation of LINE-1 by SGs that could be an important survival mechanism for cancer cells exposed to chemotherapy drugs. The findings provide a useful clue for developing new chemotherapeutic strategies against TNBCs.